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Conserved domains on  [gi|530418161|ref|XP_005260495|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [Homo sapiens]

Protein Classification

EFh_PI-PLCgamma1 and PI-PLCc_gamma domain-containing protein( domain architecture ID 11598469)

protein containing domains PH_PLC_gamma, EFh_PI-PLCgamma1, PI-PLCc_gamma, and SH2_C-SH2_PLC_gamma_like

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
319-466 5.14e-115

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


:

Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 359.05  E-value: 5.14e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  319 PDTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIK 398
Cdd:cd08592     1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIK 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  399 EHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08592    81 EHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKKL 148
EFh_PI-PLCgamma1 cd16214
EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, ...
156-306 1.20e-95

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, or PLC-148, or phospholipase C-II (PLC-II), or phospholipase C-gamma-1 (PLC-gamma-1), is abundantly expressed in embryonal cortical structures, neurons, oligodendrocytes and astrocytes, and is involved in various cellular events, including proliferation, differentiation, migration, survival, and cell death. It also associates with many diseases, including epilepsy, Huntington's disease (HD), depression, Alzheimer's disease (AD) and bipolar disorder. PI-PLC-gamma1 plays a critical role in cell migration and tumor cell invasiveness and metastasis. It can mediate the cell motility effects of growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), as well as adhesion receptors. Moreover, PI-PLC-gamma1 can modulate neurite outgrowth, neuronal cell migration and synaptic plasticity through the Trk receptor. PI-PLC-gamma1 contains an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Besides, PI-PLC-gamma1 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma1 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain.


:

Pssm-ID: 320044  Cd Length: 146  Bit Score: 302.90  E-value: 1.20e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVPNMRFLRERLTDLEQRSGDITYGQFAQLYRSLMYSAQKTMDLPFLEa 235
Cdd:cd16214     1 WLRKQFYSVDRNREDRISVKDLKNMLSQVNYRVPNMKFLREKLTDLELRSGDITYGQFAQLYRSLMFDAQKTMEVPFLE- 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530418161  236 stlrAGERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVTFLFSKE 306
Cdd:cd16214    80 ----RFEEREECKISLEDFQKFLLDYQKELWATDTNQVQEFMFNFLRDPLREIEEPYFSLDEFLTFLFSKE 146
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
29-151 5.62e-73

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. Only the first PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270168  Cd Length: 121  Bit Score: 238.33  E-value: 5.62e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   29 LEVGTVMTLFYSKKsqRPERKTFQVKLETRQITWSRGADK-IEGAIDIREIKEIRPGKTSRDFDRYQEDPaFRPDQSHCF 107
Cdd:cd13362     1 LERGTVMTKFYQKK--RPERRTFQVKLETRQVVWSRGGGKrAEGAVDIREIKEIRPGKNSKDFERWPDEA-KKLDPSCCF 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 530418161  108 VILYGMEFRLKTLSLQATSEDEVNMWIKGLTWLMEDTLQAPTPL 151
Cdd:cd13362    78 VILYGTEFRLKTLSVAATSEEECDMWIKGLRYLVEDTLSASYPL 121
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
663-765 9.94e-65

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198186  Cd Length: 104  Bit Score: 214.05  E-value: 9.94e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISYY 741
Cdd:cd09932     1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSeTDPNSFAISFRAEGKIKHCRIKQEGRLFVIGTSQFESLVELVSYY 80
                          90       100
                  ....*....|....*....|....
gi 530418161  742 EKHPLYRKMKLRYPINEEALEKIG 765
Cdd:cd09932    81 EKHPLYRKIKLRYPVNEELLEKYG 104
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
545-649 8.25e-58

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 199829  Cd Length: 99  Bit Score: 194.11  E-value: 8.25e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  545 HSNEKWFHGKLGagrDGRHIAERLLTEYCIetgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFLT 624
Cdd:cd10341     1 HFTEPWFHGKLG---DGRDEAEKLLLEYCE---GGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLT 74
                          90       100
                  ....*....|....*....|....*
gi 530418161  625 DNLVFDSLYDLITHYQQVPLRCNEF 649
Cdd:cd10341    75 DNLVFDSLYELIDYYRQNPLRCAEF 99
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
954-1069 3.27e-57

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


:

Pssm-ID: 128454 [Multi-domain]  Cd Length: 115  Bit Score: 192.84  E-value: 3.27e-57
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    954 SELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAkGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGS 1033
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKS-PTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79
                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 530418161   1034 QLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTM 1069
Cdd:smart00149   80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
1087-1250 3.93e-43

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


:

Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 153.08  E-value: 3.93e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1087 PCAISIEVLGARHLPKNG---RGIVCPFVEIEVAGAEY-DSTKQKTEfvgqsvfpvillillghckplptshpilshgdl 1162
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPAdDSAKFKTK--------------------------------- 47
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1163 kpfVVAftvDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDqNFLAQATFPVKGLKTGYRAVPLKNNYSEDLELA 1242
Cdd:cd00275    48 ---VVK---NNGFNPVW-NETFEFDVTVPELAFLRFVVYDEDSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELS 119

                  ....*...
gi 530418161 1243 SLLIKIDI 1250
Cdd:cd00275   120 TLFVHIDI 127
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
791-850 1.39e-39

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212903  Cd Length: 60  Bit Score: 140.51  E-value: 1.39e-39
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  791 TFKCAVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEMV 850
Cdd:cd11970     1 TFKCAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEIS 60
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
864-933 2.11e-37

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270054  Cd Length: 105  Bit Score: 136.06  E-value: 2.11e-37
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  864 ENSPLGDLLRGVLDVPACQIAIRPEGKNNRLFVFSISMASVAHWSLDVAADSQEELQDWVKKIREVAQTA 933
Cdd:cd13234    36 ENSPLGSLLRGILDVPSCHVVKRPEGKNSRPFVFILSPKSLSDPPLDVAADSQEELQDWVQKIREVAQTA 105
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
489-523 1.33e-15

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13234:

Pssm-ID: 450165  Cd Length: 105  Bit Score: 73.66  E-value: 1.33e-15
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 530418161  489 SIKNGILYLEDPVNHEWYPHYFVLTSSKIYYSEET 523
Cdd:cd13234     1 SIKNGILYLEDPINHEWYPHFFVLTSNKIYYSEET 35
 
Name Accession Description Interval E-value
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
319-466 5.14e-115

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 359.05  E-value: 5.14e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  319 PDTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIK 398
Cdd:cd08592     1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIK 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  399 EHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08592    81 EHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKKL 148
EFh_PI-PLCgamma1 cd16214
EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, ...
156-306 1.20e-95

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, or PLC-148, or phospholipase C-II (PLC-II), or phospholipase C-gamma-1 (PLC-gamma-1), is abundantly expressed in embryonal cortical structures, neurons, oligodendrocytes and astrocytes, and is involved in various cellular events, including proliferation, differentiation, migration, survival, and cell death. It also associates with many diseases, including epilepsy, Huntington's disease (HD), depression, Alzheimer's disease (AD) and bipolar disorder. PI-PLC-gamma1 plays a critical role in cell migration and tumor cell invasiveness and metastasis. It can mediate the cell motility effects of growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), as well as adhesion receptors. Moreover, PI-PLC-gamma1 can modulate neurite outgrowth, neuronal cell migration and synaptic plasticity through the Trk receptor. PI-PLC-gamma1 contains an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Besides, PI-PLC-gamma1 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma1 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain.


Pssm-ID: 320044  Cd Length: 146  Bit Score: 302.90  E-value: 1.20e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVPNMRFLRERLTDLEQRSGDITYGQFAQLYRSLMYSAQKTMDLPFLEa 235
Cdd:cd16214     1 WLRKQFYSVDRNREDRISVKDLKNMLSQVNYRVPNMKFLREKLTDLELRSGDITYGQFAQLYRSLMFDAQKTMEVPFLE- 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530418161  236 stlrAGERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVTFLFSKE 306
Cdd:cd16214    80 ----RFEEREECKISLEDFQKFLLDYQKELWATDTNQVQEFMFNFLRDPLREIEEPYFSLDEFLTFLFSKE 146
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
322-463 3.46e-87

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 425655 [Multi-domain]  Cd Length: 142  Bit Score: 279.00  E-value: 3.46e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGKSSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKEYA 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418161   402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKH 463
Cdd:pfam00388   81 FKTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
322-464 9.40e-75

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 244.11  E-value: 9.40e-75
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80
                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161    402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHK 464
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
29-151 5.62e-73

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. Only the first PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270168  Cd Length: 121  Bit Score: 238.33  E-value: 5.62e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   29 LEVGTVMTLFYSKKsqRPERKTFQVKLETRQITWSRGADK-IEGAIDIREIKEIRPGKTSRDFDRYQEDPaFRPDQSHCF 107
Cdd:cd13362     1 LERGTVMTKFYQKK--RPERRTFQVKLETRQVVWSRGGGKrAEGAVDIREIKEIRPGKNSKDFERWPDEA-KKLDPSCCF 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 530418161  108 VILYGMEFRLKTLSLQATSEDEVNMWIKGLTWLMEDTLQAPTPL 151
Cdd:cd13362    78 VILYGTEFRLKTLSVAATSEEECDMWIKGLRYLVEDTLSASYPL 121
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
663-765 9.94e-65

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 214.05  E-value: 9.94e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISYY 741
Cdd:cd09932     1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSeTDPNSFAISFRAEGKIKHCRIKQEGRLFVIGTSQFESLVELVSYY 80
                          90       100
                  ....*....|....*....|....
gi 530418161  742 EKHPLYRKMKLRYPINEEALEKIG 765
Cdd:cd09932    81 EKHPLYRKIKLRYPVNEELLEKYG 104
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
545-649 8.25e-58

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 194.11  E-value: 8.25e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  545 HSNEKWFHGKLGagrDGRHIAERLLTEYCIetgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFLT 624
Cdd:cd10341     1 HFTEPWFHGKLG---DGRDEAEKLLLEYCE---GGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLT 74
                          90       100
                  ....*....|....*....|....*
gi 530418161  625 DNLVFDSLYDLITHYQQVPLRCNEF 649
Cdd:cd10341    75 DNLVFDSLYELIDYYRQNPLRCAEF 99
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
954-1069 3.27e-57

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 128454 [Multi-domain]  Cd Length: 115  Bit Score: 192.84  E-value: 3.27e-57
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    954 SELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAkGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGS 1033
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKS-PTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79
                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 530418161   1034 QLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTM 1069
Cdd:smart00149   80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
977-1057 1.25e-56

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.


Pssm-ID: 176564 [Multi-domain]  Cd Length: 229  Bit Score: 196.02  E-value: 1.25e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  977 YRDMSSFPETKAEKYVNKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMT 1056
Cdd:cd08627   149 YRDMSSFPETKAEKYVNRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFML 228

                  .
gi 530418161 1057 G 1057
Cdd:cd08627   229 G 229
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
953-1067 1.50e-52

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


Pssm-ID: 425654  Cd Length: 114  Bit Score: 179.58  E-value: 1.50e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   953 LSELVVYCRPVPFDEEKIGTERACYrDMSSFPETKAEKYVnKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICG 1032
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSLPEAKTPN-HIFSFSESKALKLI-KDSQAELVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCG 78
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 530418161  1033 SQLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPS 1067
Cdd:pfam00387   79 VQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPE 113
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
1087-1250 3.93e-43

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 153.08  E-value: 3.93e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1087 PCAISIEVLGARHLPKNG---RGIVCPFVEIEVAGAEY-DSTKQKTEfvgqsvfpvillillghckplptshpilshgdl 1162
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPAdDSAKFKTK--------------------------------- 47
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1163 kpfVVAftvDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDqNFLAQATFPVKGLKTGYRAVPLKNNYSEDLELA 1242
Cdd:cd00275    48 ---VVK---NNGFNPVW-NETFEFDVTVPELAFLRFVVYDEDSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELS 119

                  ....*...
gi 530418161 1243 SLLIKIDI 1250
Cdd:cd00275   120 TLFVHIDI 127
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
791-850 1.39e-39

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212903  Cd Length: 60  Bit Score: 140.51  E-value: 1.39e-39
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  791 TFKCAVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEMV 850
Cdd:cd11970     1 TFKCAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEIS 60
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
864-933 2.11e-37

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270054  Cd Length: 105  Bit Score: 136.06  E-value: 2.11e-37
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  864 ENSPLGDLLRGVLDVPACQIAIRPEGKNNRLFVFSISMASVAHWSLDVAADSQEELQDWVKKIREVAQTA 933
Cdd:cd13234    36 ENSPLGSLLRGILDVPSCHVVKRPEGKNSRPFVFILSPKSLSDPPLDVAADSQEELQDWVQKIREVAQTA 105
PLN02228 PLN02228
Phosphoinositide phospholipase C
248-551 2.10e-34

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 140.56  E-value: 2.10e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  248 RVSLPEFQQFLLDYQGELWAvdrlqvqefMLSFLRDPLREIEEPYFF-------LDEFVTFLFSKENS-------VWNSq 313
Cdd:PLN02228   38 KMSFDELLRFVSEVQGERHA---------GLDYVQDIFHSVKHHNVFhhhglvhLNAFYRYLFSDTNSplpmsgqVHHD- 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  314 ldavcpdtMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPV-IYHGHTLTTKIKFSD 392
Cdd:PLN02228  108 --------MKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAeVRHGRTLTSHEDLQK 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  393 VLHTIKEHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEiSADGLPSPNQLKRKILIKHKKLAEgsaY 472
Cdd:PLN02228  180 CLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSE-STKHFPSPEELKNKILISTKPPKE---Y 255
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  473 EEVPTSMMYSENDISNSIKNGILYLEDPVNHEWYPhyfvLTSSKIYYSEETSSDQGN----------EDEEEPKEVSSSt 542
Cdd:PLN02228  256 LESKTVQTTRTPTVKETSWKRVADAENKILEEYKD----EESEAVGYRDLIAIHAANckdplkdclsDDPEKPIRVSMD- 330

                  ....*....
gi 530418161  543 elhsnEKWF 551
Cdd:PLN02228  331 -----EQWL 334
SH2 pfam00017
SH2 domain;
550-639 4.30e-27

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 105.38  E-value: 4.30e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   550 WFHGKLGagrdgRHIAERLLTEycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDNLVF 629
Cdd:pfam00017    1 WYHGKIS-----RQEAERLLLN-----GKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNG---GYYISGGVKF 67
                           90
                   ....*....|
gi 530418161   630 DSLYDLITHY 639
Cdd:pfam00017   68 SSLAELVEHY 77
PLN02228 PLN02228
Phosphoinositide phospholipase C
994-1252 3.58e-25

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 112.05  E-value: 3.58e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  994 KAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTMRDEA 1073
Cdd:PLN02228  339 RTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEH 418
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1074 --FDPFDKSSLRGLEPCAISIEVLGARHLPKNGRGIVCP---FVEIEVAGAEYDSTKQKTEFVGQSVFpvillillghck 1148
Cdd:PLN02228  419 tlFDPCKRLPIKTTLKVKIYTGEGWDLDFHLTHFDQYSPpdfFVKIGIAGVPRDTVSYRTETAVDQWF------------ 486
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1149 plptshpilshgdlkpfvvaftvdnglnPVWPAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRA 1228
Cdd:PLN02228  487 ----------------------------PIWGNDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRA 538
                         250       260
                  ....*....|....*....|....
gi 530418161 1229 VPLKNNYSEDLELASLLIKIDIFP 1252
Cdd:PLN02228  539 VRLHDRAGKAYKNTRLLVSFALDP 562
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
548-645 5.95e-25

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 99.61  E-value: 5.95e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    548 EKWFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDNL 627
Cdd:smart00252    1 QPWYHGFIS-----REEAEKLLK------NEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDG---KFYLEGGR 66
                            90
                    ....*....|....*...
gi 530418161    628 VFDSLYDLITHYQQVPLR 645
Cdd:smart00252   67 KFPSLVELVEHYQKNSLG 84
SH2 pfam00017
SH2 domain;
668-741 4.16e-24

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 96.90  E-value: 4.16e-24
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161   668 WYHASLTRAQAEHMLMRVPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLGNSEFDSLVDLISYY 741
Cdd:pfam00017    1 WYHGKISRQEAERLLLNGKPDGTFLVRESeSTPGGYTLSVRDDGKVKHYKIQStdNGGYYISGGVKFSSLAELVEHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
667-747 1.84e-21

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 89.60  E-value: 1.84e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    667 EWYHASLTRAQAEHMLMRVPrDGAFLVRK-RNEPNSYAISFRAEGKIKHCRVQQ-EGQTVMLGNSE-FDSLVDLISYYEK 743
Cdd:smart00252    2 PWYHGFISREEAEKLLKNEG-DGDFLVRDsESSPGDYVLSVRVKGKVKHYRIRRnEDGKFYLEGGRkFPSLVELVEHYQK 80

                    ....
gi 530418161    744 HPLY 747
Cdd:smart00252   81 NSLG 84
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
796-847 3.55e-17

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 76.42  E-value: 3.55e-17
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 530418161    796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
489-523 1.33e-15

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270054  Cd Length: 105  Bit Score: 73.66  E-value: 1.33e-15
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 530418161  489 SIKNGILYLEDPVNHEWYPHYFVLTSSKIYYSEET 523
Cdd:cd13234     1 SIKNGILYLEDPINHEWYPHFFVLTSNKIYYSEET 35
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
797-843 1.54e-15

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 71.47  E-value: 1.54e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 530418161   797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPS 843
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1090-1231 6.32e-13

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 65.97  E-value: 6.32e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   1090 ISIEVLGARHLP-KNGRGIVCPFVEIEVAGAeyDSTKQKTEfvgqsvfpvillillghckplptshpilshgdlkpfvva 1168
Cdd:smart00239    2 LTVKIISARNLPpKDKGGKSDPYVKVSLDGD--PKEKKKTK--------------------------------------- 40
                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161   1169 fTVDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRAVPL 1231
Cdd:smart00239   41 -VVKNTLNPVW-NETFEFEVPPPELAELEIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
1090-1228 4.59e-11

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 60.80  E-value: 4.59e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  1090 ISIEVLGARHLP-KNGRGIVCPFVEIEVAGaeyDSTKQKTEfvgqsvfpvillillghckplptshpilshgdlkpfvva 1168
Cdd:pfam00168    3 LTVTVIEAKNLPpKDGNGTSDPYVKVYLLD---GKQKKKTK--------------------------------------- 40
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  1169 fTVDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRA 1228
Cdd:pfam00168   41 -VVKNTLNPVW-NETFTFSVPDPENAVLEIEVYDYDRFGRDDFIGEVRIPLSELDSGEGL 98
PH pfam00169
PH domain; PH stands for pleckstrin homology.
71-142 2.84e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 41.39  E-value: 2.84e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418161    71 GAIDIREIKEIRPGKTSRdfdryqedpafrPDQSHCFVILYGMEFRLKTLSLQATSEDEVNMWIKGLTWLME 142
Cdd:pfam00169   46 GSISLSGCEVVEVVASDS------------PKRKFCFELRTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
863-931 8.94e-04

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 39.84  E-value: 8.94e-04
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    863 DENSPLGDLLRGVLDVPACQIAIRPEGKN-NRLFVFSISMASvaHWSLDVAADSQEELQDWVKKIREVAQ 931
Cdd:smart00233   35 SKKDKKSYKPKGSIDLSGCTVREAPDPDSsKKPHCFEIKTSD--RKTLLLQAESEEEREKWVEALRKAIA 102
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
36-137 1.99e-03

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 39.07  E-value: 1.99e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161     36 TLFYSKKSQRPERKTFQVKLETRQITW-----SRGADKIEGAIDIREIkEIRPGKTSRDFDRyqedpafrpdqSHCFVIL 110
Cdd:smart00233    6 WLYKKSGGGKKSWKKRYFVLFNSTLLYykskkDKKSYKPKGSIDLSGC-TVREAPDPDSSKK-----------PHCFEIK 73
                            90       100
                    ....*....|....*....|....*..
gi 530418161    111 YGMEfrlKTLSLQATSEDEVNMWIKGL 137
Cdd:smart00233   74 TSDR---KTLLLQAESEEEREKWVEAL 97
 
Name Accession Description Interval E-value
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
319-466 5.14e-115

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 359.05  E-value: 5.14e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  319 PDTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIK 398
Cdd:cd08592     1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIK 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  399 EHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08592    81 EHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKKL 148
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
319-466 8.50e-111

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.


Pssm-ID: 176564 [Multi-domain]  Cd Length: 229  Bit Score: 347.79  E-value: 8.50e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  319 PDTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIK 398
Cdd:cd08627     1 PEEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIK 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  399 EHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08627    81 EHAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDINADGLPSPNQLKRKILIKHKKL 148
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
322-473 1.95e-100

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity.


Pssm-ID: 176501 [Multi-domain]  Cd Length: 226  Bit Score: 319.01  E-value: 1.95e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08558     4 MTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIKEYA 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKK-----LAEGSAYE 473
Cdd:cd08558    84 FVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQLPSPEQLKGKILIKGKKyhmssFSETKALK 160
EFh_PI-PLCgamma1 cd16214
EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, ...
156-306 1.20e-95

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, or PLC-148, or phospholipase C-II (PLC-II), or phospholipase C-gamma-1 (PLC-gamma-1), is abundantly expressed in embryonal cortical structures, neurons, oligodendrocytes and astrocytes, and is involved in various cellular events, including proliferation, differentiation, migration, survival, and cell death. It also associates with many diseases, including epilepsy, Huntington's disease (HD), depression, Alzheimer's disease (AD) and bipolar disorder. PI-PLC-gamma1 plays a critical role in cell migration and tumor cell invasiveness and metastasis. It can mediate the cell motility effects of growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), as well as adhesion receptors. Moreover, PI-PLC-gamma1 can modulate neurite outgrowth, neuronal cell migration and synaptic plasticity through the Trk receptor. PI-PLC-gamma1 contains an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Besides, PI-PLC-gamma1 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma1 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain.


Pssm-ID: 320044  Cd Length: 146  Bit Score: 302.90  E-value: 1.20e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVPNMRFLRERLTDLEQRSGDITYGQFAQLYRSLMYSAQKTMDLPFLEa 235
Cdd:cd16214     1 WLRKQFYSVDRNREDRISVKDLKNMLSQVNYRVPNMKFLREKLTDLELRSGDITYGQFAQLYRSLMFDAQKTMEVPFLE- 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530418161  236 stlrAGERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVTFLFSKE 306
Cdd:cd16214    80 ----RFEEREECKISLEDFQKFLLDYQKELWATDTNQVQEFMFNFLRDPLREIEEPYFSLDEFLTFLFSKE 146
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
322-463 3.46e-87

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 425655 [Multi-domain]  Cd Length: 142  Bit Score: 279.00  E-value: 3.46e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGKSSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKEYA 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418161   402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKH 463
Cdd:pfam00388   81 FKTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
319-466 1.08e-86

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 176565 [Multi-domain]  Cd Length: 254  Bit Score: 282.33  E-value: 1.08e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  319 PDTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIK 398
Cdd:cd08628     1 PQDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIK 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  399 EHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08628    81 DHAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEASADQLPSPTQLKEKIIIKHKKL 148
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
322-466 5.72e-79

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD.


Pssm-ID: 176535 [Multi-domain]  Cd Length: 257  Bit Score: 260.73  E-value: 5.72e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08593     4 MTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIREYA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08593    84 FKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEELKGKILVKGKKL 148
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
322-464 9.40e-75

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 244.11  E-value: 9.40e-75
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80
                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161    402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHK 464
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
29-151 5.62e-73

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. Only the first PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270168  Cd Length: 121  Bit Score: 238.33  E-value: 5.62e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   29 LEVGTVMTLFYSKKsqRPERKTFQVKLETRQITWSRGADK-IEGAIDIREIKEIRPGKTSRDFDRYQEDPaFRPDQSHCF 107
Cdd:cd13362     1 LERGTVMTKFYQKK--RPERRTFQVKLETRQVVWSRGGGKrAEGAVDIREIKEIRPGKNSKDFERWPDEA-KKLDPSCCF 77
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 530418161  108 VILYGMEFRLKTLSLQATSEDEVNMWIKGLTWLMEDTLQAPTPL 151
Cdd:cd13362    78 VILYGTEFRLKTLSVAATSEEECDMWIKGLRYLVEDTLSASYPL 121
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
322-491 1.41e-72

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 176540 [Multi-domain]  Cd Length: 231  Bit Score: 241.77  E-value: 1.41e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08598     4 LSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKKYA 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKlaegsayEEVPTSMMY 481
Cdd:cd08598    84 FVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDELPSPEELRGKILIKVKK-------ESKTPNHIF 156
                         170
                  ....*....|..
gi 530418161  482 S--ENDISNSIK 491
Cdd:cd08598   157 SlsERSLLKLLK 168
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
318-466 2.41e-72

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 176539 [Multi-domain]  Cd Length: 260  Bit Score: 241.94  E-value: 2.41e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  318 CPDtMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTI 397
Cdd:cd08597     1 CQD-MTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAI 79
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530418161  398 KEHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08597    80 NEYAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPHDLKGKIIIKGKKL 148
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
322-466 3.92e-70

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.


Pssm-ID: 176533 [Multi-domain]  Cd Length: 257  Bit Score: 235.69  E-value: 3.92e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTIKE 399
Cdd:cd08591     4 MDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEAIAE 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530418161  400 HAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVE----ISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08591    84 TAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEkyplEPGVPLPSPNDLKRKILIKNKKL 154
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
322-465 7.69e-70

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 176536 [Multi-domain]  Cd Length: 227  Bit Score: 233.54  E-value: 7.69e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08594     4 MTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINKYA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTL-LTKPVEISADGLPSPNQLKRKILIKHKK 465
Cdd:cd08594    84 FIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLdLSSVISGDSKQLPSPQSLKGKILIKGKK 148
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
320-470 5.13e-68

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176538 [Multi-domain]  Cd Length: 254  Bit Score: 229.74  E-value: 5.13e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  320 DTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 399
Cdd:cd08596     2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  400 HAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTK---PVEISAD-GLPSPNQLKRKILIKHKKLAEGS 470
Cdd:cd08596    82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKflfESDFSDDpSLPSPLQLKNKILLKNKKAPELS 156
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
322-466 9.12e-66

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation.


Pssm-ID: 176566 [Multi-domain]  Cd Length: 258  Bit Score: 223.37  E-value: 9.12e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08629     4 MDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRDYA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08629    84 FKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVTTSLPSPEQLKGKILLKGKKL 148
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
322-466 2.20e-65

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus.


Pssm-ID: 176567 [Multi-domain]  Cd Length: 258  Bit Score: 222.20  E-value: 2.20e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08630     4 MSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQHA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPV-EISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08630    84 FTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLdSLNPEELPSPEELKGRVLVKGKKL 149
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
156-306 5.48e-65

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 216.28  E-value: 5.48e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVpNMRFLRERLTDLE-QRSGDITYGQFAQLYRSLMYSaQKTMDLPFLE 234
Cdd:cd16201     1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKI-STNKLREKFQEVDtRRRGELGFDDFAQLYHKLMFD-QKIIEDFFKK 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418161  235 AStlragERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVTFLFSKE 306
Cdd:cd16201    79 YS-----YSSDGQTVTLEDFQRFLLEEQKEPWANDPNAVREFMRDFLQDPLRDVQEPYFTLDEFLDYLFSKE 145
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
663-765 9.94e-65

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 214.05  E-value: 9.94e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISYY 741
Cdd:cd09932     1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSeTDPNSFAISFRAEGKIKHCRIKQEGRLFVIGTSQFESLVELVSYY 80
                          90       100
                  ....*....|....*....|....
gi 530418161  742 EKHPLYRKMKLRYPINEEALEKIG 765
Cdd:cd09932    81 EKHPLYRKIKLRYPVNEELLEKYG 104
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
322-467 1.05e-63

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 217.22  E-value: 1.05e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08633     4 MTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTL-LTKPVEISADGLPSPNQLKRKILIKHKKLA 467
Cdd:cd08633    84 FIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLdLSSVISNDCTRLPSPEILKGKILVKGKKLS 150
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
322-467 1.59e-62

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain.


Pssm-ID: 176569 [Multi-domain]  Cd Length: 253  Bit Score: 213.74  E-value: 1.59e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08632     4 MDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETINKYA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTL-LTKPVEISADGLPSPNQLKRKILIKHKKLA 467
Cdd:cd08632    84 FVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLdLSSVLTGDPKQLPSPQLLKGKILVKGKKLC 150
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
322-465 1.83e-62

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176537 [Multi-domain]  Cd Length: 257  Bit Score: 213.64  E-value: 1.83e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08595     4 MDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEKYA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPV-EISADGLPSPNQLKRKILIKHKK 465
Cdd:cd08595    84 FEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIdDPATGELPSPEALKFKILVKNKK 148
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
322-467 2.16e-61

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176563 [Multi-domain]  Cd Length: 257  Bit Score: 210.78  E-value: 2.16e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGP--DGMPVIYHGHTLTTKIKFSDVLHTIKE 399
Cdd:cd08626     4 MDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQAIKD 83
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418161  400 HAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVE----ISADGLPSPNQLKRKILIKHKKLA 467
Cdd:cd08626    84 TAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLEshplEPGVPLPSPNKLKRKILIKNKRLS 155
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
322-466 7.72e-61

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.


Pssm-ID: 176568 [Multi-domain]  Cd Length: 258  Bit Score: 209.03  E-value: 7.72e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08631     4 MTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQYA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVE-ISADGLPSPNQLKRKILIKHKKL 466
Cdd:cd08631    84 FQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDgVLPTQLPSPEELRGKILLKGKKI 149
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
545-649 8.25e-58

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 194.11  E-value: 8.25e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  545 HSNEKWFHGKLGagrDGRHIAERLLTEYCIetgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFLT 624
Cdd:cd10341     1 HFTEPWFHGKLG---DGRDEAEKLLLEYCE---GGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLT 74
                          90       100
                  ....*....|....*....|....*
gi 530418161  625 DNLVFDSLYDLITHYQQVPLRCNEF 649
Cdd:cd10341    75 DNLVFDSLYELIDYYRQNPLRCAEF 99
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
954-1069 3.27e-57

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 128454 [Multi-domain]  Cd Length: 115  Bit Score: 192.84  E-value: 3.27e-57
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    954 SELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAkGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGS 1033
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKS-PTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79
                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 530418161   1034 QLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTM 1069
Cdd:smart00149   80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
977-1057 1.25e-56

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.


Pssm-ID: 176564 [Multi-domain]  Cd Length: 229  Bit Score: 196.02  E-value: 1.25e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  977 YRDMSSFPETKAEKYVNKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMT 1056
Cdd:cd08627   149 YRDMSSFPETKAEKYVNRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFML 228

                  .
gi 530418161 1057 G 1057
Cdd:cd08627   229 G 229
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
322-464 3.61e-53

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 186.04  E-value: 3.61e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHA 401
Cdd:cd08599     4 MTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKENA 83
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161  402 FVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHK 464
Cdd:cd08599    84 FTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDLPEEFPSPEELKGKILISDK 146
EFh_PI-PLCgamma1_like cd16216
EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...
156-306 1.39e-52

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like proteins; This family corresponds to a small group of uncharacterized 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like (PI-PLC-gamma1-like) proteins. Although their biological function remains unclear, they shows high sequence similarity with other phosphoinositide phospholipase C gamma proteins. They contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. A second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker.


Pssm-ID: 320046  Cd Length: 150  Bit Score: 181.28  E-value: 1.39e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVPNMRFLRERLTDLEQRSgDITYGQFAQLYRSLMYSAQKTMdLPFLEA 235
Cdd:cd16216     1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPNMRFLRDKLVEVEARS-ELTFPHFIQFYKNLMFDAQKSI-IEQLEL 78
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418161  236 S-TLRAGERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVTFLFSKE 306
Cdd:cd16216    79 SfPLRNVDRPELCQISLYDFQKFLQHDQKESWASDVGRVRDYLCGYLKESSNEAPEPSLQLDEFLTYLFSKE 150
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
953-1067 1.50e-52

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


Pssm-ID: 425654  Cd Length: 114  Bit Score: 179.58  E-value: 1.50e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   953 LSELVVYCRPVPFDEEKIGTERACYrDMSSFPETKAEKYVnKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICG 1032
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSLPEAKTPN-HIFSFSESKALKLI-KDSQAELVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCG 78
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 530418161  1033 SQLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPS 1067
Cdd:pfam00387   79 VQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPE 113
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
977-1057 2.80e-52

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 183.40  E-value: 2.80e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  977 YRDMSSFPETKAEKYVNKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMT 1056
Cdd:cd08592   149 FYEMSSFPETKAEKYLNRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFML 228

                  .
gi 530418161 1057 G 1057
Cdd:cd08592   229 N 229
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
322-481 4.02e-52

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176561 [Multi-domain]  Cd Length: 261  Bit Score: 184.10  E-value: 4.02e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTIKE 399
Cdd:cd08624     4 MTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEAIAE 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  400 HAFVASEYPVILSIEDHC-SIAQQRNMAQYFKKVLGDTLLTKPVE----ISADGLPSPNQLKRKILIKHKKlaegsaYEE 474
Cdd:cd08624    84 SAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEkyplKPGVPLPSPEDLRGKILIKNKK------YEE 157

                  ....*..
gi 530418161  475 VPTSMMY 481
Cdd:cd08624   158 MSSLVNY 164
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
320-474 5.40e-49

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176562 [Multi-domain]  Cd Length: 258  Bit Score: 175.24  E-value: 5.40e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  320 DTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTI 397
Cdd:cd08625     2 DDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAI 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  398 KEHAFVASEYPVILSIEDHC-SIAQQRNMAQYFKKVLGDTLLTKPVE----ISADGLPSPNQLKRKILIKHKKLAEGSAY 472
Cdd:cd08625    82 AESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplVPGVQLPSPQELMGKILVKNKKMSTLVNY 161

                  ..
gi 530418161  473 EE 474
Cdd:cd08625   162 IE 163
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
1087-1250 3.93e-43

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 153.08  E-value: 3.93e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1087 PCAISIEVLGARHLPKNG---RGIVCPFVEIEVAGAEY-DSTKQKTEfvgqsvfpvillillghckplptshpilshgdl 1162
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPAdDSAKFKTK--------------------------------- 47
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1163 kpfVVAftvDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDqNFLAQATFPVKGLKTGYRAVPLKNNYSEDLELA 1242
Cdd:cd00275    48 ---VVK---NNGFNPVW-NETFEFDVTVPELAFLRFVVYDEDSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELS 119

                  ....*...
gi 530418161 1243 SLLIKIDI 1250
Cdd:cd00275   120 TLFVHIDI 127
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
322-466 3.04e-42

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176497 [Multi-domain]  Cd Length: 274  Bit Score: 156.27  E-value: 3.04e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  322 MNNPLSHYWISSSHNTYLTGDQFSSE-----SSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLtTKIKFSDVLHT 396
Cdd:cd00137     4 DTQPLAHYSIPGTHDTYLTAGQFTIKqvwglTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTF-LDIFLKEVIEA 82
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530418161  397 IKEHAFVASEYPVILSIEDHCSI--AQQRNMAQYFKKVLGDTLLTKPVEISaDGLPSPNQLKRKILIKHKKL 466
Cdd:cd00137    83 IAQFLKKNPPETIIMSLKNEVDSmdSFQAKMAEYCRTIFGDMLLTPPLKPT-VPLPSLEDLRGKILLLNKKN 153
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
320-467 9.15e-42

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176560 [Multi-domain]  Cd Length: 258  Bit Score: 154.47  E-value: 9.15e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  320 DTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTI 397
Cdd:cd08623     2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  398 KEHAFVASEYPVILSIEDHC-SIAQQRNMAQYFKKVLGDTLLTKPVEI----SADGLPSPNQLKRKILIKHKKLA 467
Cdd:cd08623    82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKypleSGVPLPSPMDLMYKILVKNKKMS 156
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
935-1054 1.62e-41

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 176565 [Multi-domain]  Cd Length: 254  Bit Score: 153.29  E-value: 1.62e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  935 ARLTEGKIMERRKKIALELSELVVYCRPVpfDEEKIGTERACYRDMSSFPETKAEKYVnKAKGKKFLQYNRLQLSRIYPK 1014
Cdd:cd08628   135 TQLKEKIIIKHKKLIAIELSDLVVYCKPT--SKTKDNLENPDFKEIRSFVETKAPSII-RQKPVQLLKYNRKGLTRVYPK 211
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 530418161 1015 GQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08628   212 GQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALF 251
EFh_PI-PLCgamma2 cd16215
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed ...
156-306 3.06e-40

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, or phospholipase C-IV (PLC-IV), or phospholipase C-gamma-2 (PLC-gamma-2), is highly expressed in cells of hematopoietic origin. It has been implicated in cell motility important to invasion and dissemination of tumor cells. As an important component of the B cell receptor (BCR) signaling pathway, PI-PLC-gamma2 is required for efficient formation of germinal center (GC) and memory B cells. It works as a critical effector stimulating the increase of intracellular Ca2+ and activates various signaling pathways downstream of the BCR. Moreover, PI-PLC-gamma2 has been implicated in Fc receptor-mediated degranulation of mast cells, integrin signaling in platelets, as well as integrin and Fc receptor-mediated neutrophil functions. It also acts as a crucial signaling mediator modifying DC gene expression program to activate DC responses to beta-glucan-containing pathogens. PI-PLC-gamma2 contains an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Besides, PI-PLC-gamma2 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma2 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 320045  Cd Length: 154  Bit Score: 146.15  E-value: 3.06e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVPNMRFLRERLTDLEQRSGDITYGQFAQLYRSLMYSAQKTMDLPFLEA 235
Cdd:cd16215     1 WLRKQIYSVDQTRRNSISVRELKTILPQVNFKVPSAKFLKDKFQEIGAKKDELTFEQFHLFYKKLMFEQQKSILDEFKKD 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418161  236 ST---LRAGERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVTFLFSKE 306
Cdd:cd16215    81 SSvfiLGNTDRPDASAVHLHDFQRFLVHEQKESWAQDLNKVRERMTKFIDDTMRETAEPFLFVDEFLTYLFSKE 154
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
791-850 1.39e-39

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212903  Cd Length: 60  Bit Score: 140.51  E-value: 1.39e-39
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  791 TFKCAVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEMV 850
Cdd:cd11970     1 TFKCAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEIS 60
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
940-1054 1.84e-38

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.


Pssm-ID: 176533 [Multi-domain]  Cd Length: 257  Bit Score: 144.79  E-value: 1.84e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKKialeLSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVnKAKGKKFLQYNRLQLSRIYPKGQRLD 1019
Cdd:cd08591   145 RKILIKNKK----LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYL-KKSPIEFVNYNKRQLSRIYPKGTRVD 219
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530418161 1020 SSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08591   220 SSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKF 254
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
940-1054 2.32e-38

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD.


Pssm-ID: 176535 [Multi-domain]  Cd Length: 257  Bit Score: 144.40  E-value: 2.32e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKKI--ALELSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKaKGKKFLQYNRLQLSRIYPKGQR 1017
Cdd:cd08593   139 GKILVKGKKLklAKELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQE-SGNEFVRHNKRQLSRIYPAGLR 217
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 530418161 1018 LDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08593   218 TDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLF 254
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
977-1055 4.52e-38

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity.


Pssm-ID: 176501 [Multi-domain]  Cd Length: 226  Bit Score: 142.59  E-value: 4.52e-38
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530418161  977 YRDMSSFPETKAEKYVNKaKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFM 1055
Cdd:cd08558   147 KYHMSSFSETKALKLLKE-SPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFE 224
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
864-933 2.11e-37

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270054  Cd Length: 105  Bit Score: 136.06  E-value: 2.11e-37
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  864 ENSPLGDLLRGVLDVPACQIAIRPEGKNNRLFVFSISMASVAHWSLDVAADSQEELQDWVKKIREVAQTA 933
Cdd:cd13234    36 ENSPLGSLLRGILDVPSCHVVKRPEGKNSRPFVFILSPKSLSDPPLDVAADSQEELQDWVQKIREVAQTA 105
PLN02228 PLN02228
Phosphoinositide phospholipase C
248-551 2.10e-34

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 140.56  E-value: 2.10e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  248 RVSLPEFQQFLLDYQGELWAvdrlqvqefMLSFLRDPLREIEEPYFF-------LDEFVTFLFSKENS-------VWNSq 313
Cdd:PLN02228   38 KMSFDELLRFVSEVQGERHA---------GLDYVQDIFHSVKHHNVFhhhglvhLNAFYRYLFSDTNSplpmsgqVHHD- 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  314 ldavcpdtMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPV-IYHGHTLTTKIKFSD 392
Cdd:PLN02228  108 --------MKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAeVRHGRTLTSHEDLQK 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  393 VLHTIKEHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEiSADGLPSPNQLKRKILIKHKKLAEgsaY 472
Cdd:PLN02228  180 CLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSE-STKHFPSPEELKNKILISTKPPKE---Y 255
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  473 EEVPTSMMYSENDISNSIKNGILYLEDPVNHEWYPhyfvLTSSKIYYSEETSSDQGN----------EDEEEPKEVSSSt 542
Cdd:PLN02228  256 LESKTVQTTRTPTVKETSWKRVADAENKILEEYKD----EESEAVGYRDLIAIHAANckdplkdclsDDPEKPIRVSMD- 330

                  ....*....
gi 530418161  543 elhsnEKWF 551
Cdd:PLN02228  331 -----EQWL 334
PLN02222 PLN02222
phosphoinositide phospholipase C 2
295-475 1.44e-32

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 135.16  E-value: 1.44e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  295 LDEFVTFLFSKENSVWNSQldAVCPDtMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCW--DGP 372
Cdd:PLN02222   81 LDAFFKYLFGDNNPPLALH--EVHHD-MDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWpnSDK 157
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  373 DGMPVIyHGHTLTTKIKFSDVLHTIKEHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLPSP 452
Cdd:PLN02222  158 DDIDVL-HGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVGESLKEFPSP 236
                         170       180
                  ....*....|....*....|...
gi 530418161  453 NQLKRKILIKHKKLAEGSAYEEV 475
Cdd:PLN02222  237 NSLKKRIIISTKPPKEYKEGKDD 259
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
795-848 3.42e-32

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 119.36  E-value: 3.42e-32
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  795 AVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEE 848
Cdd:cd11825     1 TVKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKKQKWFPANYVEE 54
PLN02952 PLN02952
phosphoinositide phospholipase C
253-582 5.46e-31

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 130.50  E-value: 5.46e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  253 EFQQFLLDYQGELwAVDRLQVQEFMLSFL--RDPLREIEEPYFFLDEFVTFLFSKEnsvWNSQLDAVCPDTMNNPLSHYW 330
Cdd:PLN02952   58 QLRRFLVLHQDEL-DCTLAEAQRIVEEVInrRHHVTRYTRHGLNLDDFFHFLLYDD---LNGPITPQVHHDMTAPLSHYF 133
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  331 ISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPV-IYHGHTLTTKIKFSDVLHTIKEHAFVASEYPV 409
Cdd:PLN02952  134 IYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPV 213
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  410 ILSIEDHCSIAQQRNMAQYFKKVLGDTLLTkPVEISADGLPSPNQLKRKILIKHKKlaegsayeevPTSMMYSENDISNS 489
Cdd:PLN02952  214 IITLEDHLTPDLQAKVAEMATQIFGQMLYY-PESDSLVQFPSPESLKHRIIISTKP----------PKEYLESSGPIVIK 282
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  490 IKNGilyledpvnhewyphyfvLTSSKIYYSEETSSDQGNEDEEEPKEVSSSTELHSNEKwfhgklGAGRDGRHIAERLL 569
Cdd:PLN02952  283 KKNN------------------VSPSGRNSSEETEEAQTLESMLFEQEADSRSDSDQDDN------KSGELQKPAYKRLI 338
                         330
                  ....*....|...
gi 530418161  570 TeycIETGAPDGS 582
Cdd:PLN02952  339 T---IHAGKPKGT 348
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
939-1054 1.61e-30

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176563 [Multi-domain]  Cd Length: 257  Bit Score: 121.80  E-value: 1.61e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  939 EGKIMERRKKialeLSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVnKAKGKKFLQYNRLQLSRIYPKGQRL 1018
Cdd:cd08626   144 KRKILIKNKR----LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYL-KTSAIEFVNYNKRQMSRIYPKGTRV 218
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 530418161 1019 DSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08626   219 DSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKF 254
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
29-141 2.57e-30

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269952  Cd Length: 108  Bit Score: 115.88  E-value: 2.57e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   29 LEVGTVMTLFYSKKSqrPERKTFQVKLETRQITWSRGADKIEGA-IDIREIKEIRPGKTSRDFDRYQedPAFRPDQSHCF 107
Cdd:cd01248     1 LQQGTLLLKYREGSK--PKERTFYLDPDGTRITWESSKKKSEKKsIDISDIKEIRPGKDTDGFKRKK--KSNKPKEERCF 76
                          90       100       110
                  ....*....|....*....|....*....|....
gi 530418161  108 VILYGMEFrlKTLSLQATSEDEVNMWIKGLTWLM 141
Cdd:cd01248    77 SIIYGSNN--KTLDLVAPSEDEANLWVEGLRALL 108
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
940-1054 2.92e-30

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176561 [Multi-domain]  Cd Length: 261  Bit Score: 121.32  E-value: 2.92e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKKIAlELSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAkGKKFLQYNRLQLSRIYPKGQRLD 1019
Cdd:cd08624   146 GKILIKNKKYE-EMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKA-SVQFVEYNKRQMSRIYPKGTRMD 223
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530418161 1020 SSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08624   224 SSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALF 258
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
940-1054 3.04e-30

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.


Pssm-ID: 176568 [Multi-domain]  Cd Length: 258  Bit Score: 120.82  E-value: 3.04e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKKIAL--ELSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAkGKKFLQYNRLQLSRIYPKGQR 1017
Cdd:cd08631   140 GKILLKGKKIRLspELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREA-GNEFVQHNTWQLSRVYPSGLR 218
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 530418161 1018 LDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08631   219 TDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLF 255
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
939-1054 3.37e-30

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation.


Pssm-ID: 176566 [Multi-domain]  Cd Length: 258  Bit Score: 120.91  E-value: 3.37e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  939 EGKIMERRKKIAL--ELSELVVYCRPVPFD--EEKIGTERACYrDMSSFPETKAEKYVNKAkGKKFLQYNRLQLSRIYPK 1014
Cdd:cd08629   138 KGKILLKGKKLKLvpELSDMIIYCKSVHFGgfSSPGTSGQAFY-EMASFSESRALRLLQES-GNGFVRHNVSCLSRIYPA 215
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 530418161 1015 GQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08629   216 GWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCF 255
PLN02230 PLN02230
phosphoinositide phospholipase C 4
295-468 3.98e-29

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 124.43  E-value: 3.98e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  295 LDEFVTFLFSKEnsvWNSQLDAVCPDTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDG 374
Cdd:PLN02230   93 LDDFNYYLFSTD---LNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTD 169
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  375 MPVIYHGHTLTTKIKFSDVLHTIKEHAFVASEYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEiSADGLPSPNQ 454
Cdd:PLN02230  170 DVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYHDSE-GCQEFPSPEE 248
                         170
                  ....*....|....
gi 530418161  455 LKRKILIKHKKLAE 468
Cdd:PLN02230  249 LKEKILISTKPPKE 262
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
939-1055 4.94e-29

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus.


Pssm-ID: 176567 [Multi-domain]  Cd Length: 258  Bit Score: 117.43  E-value: 4.94e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  939 EGKIMERRKKIAL--ELSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAkGKKFLQYNRLQLSRIYPKGQ 1016
Cdd:cd08630   139 KGRVLVKGKKLQIspELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREA-GNSFVRHNARQLTRVYPLGL 217
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 530418161 1017 RLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFM 1055
Cdd:cd08630   218 RMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFL 256
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
940-1054 1.13e-28

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176562 [Multi-domain]  Cd Length: 258  Bit Score: 116.31  E-value: 1.13e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKKialeLSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAKgKKFLQYNRLQLSRIYPKGQRLD 1019
Cdd:cd08625   146 GKILVKNKK----MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSP-MEFVEYNKKQLSRIYPKGTRVD 220
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530418161 1020 SSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08625   221 SSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVF 255
SH2 pfam00017
SH2 domain;
550-639 4.30e-27

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 105.38  E-value: 4.30e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   550 WFHGKLGagrdgRHIAERLLTEycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDNLVF 629
Cdd:pfam00017    1 WYHGKIS-----RQEAERLLLN-----GKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNG---GYYISGGVKF 67
                           90
                   ....*....|
gi 530418161   630 DSLYDLITHY 639
Cdd:pfam00017   68 SSLAELVEHY 77
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
928-1055 2.77e-26

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain.


Pssm-ID: 176569 [Multi-domain]  Cd Length: 253  Bit Score: 109.35  E-value: 2.77e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  928 EVAQTADARLTEGKIMERRKKIALELSELVVYCRPVPfDEEKIGTERACyrDMSSFPETKAEKYVNKaKGKKFLQYNRLQ 1007
Cdd:cd08632   128 DPKQLPSPQLLKGKILVKGKKLCRDLSDLVVYTNSVA-AQDIVDDGSTG--NVLSFSETRAHQLVQQ-KAEQFMTYNQKQ 203
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 530418161 1008 LSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFM 1055
Cdd:cd08632   204 LTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFM 251
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
940-1054 8.39e-26

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 176539 [Multi-domain]  Cd Length: 260  Bit Score: 108.28  E-value: 8.39e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKK---IAL--ELSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAKGKkFLQYNRLQLSRIYPK 1014
Cdd:cd08597   139 GKIIIKGKKlkrRKLckELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPED-FVNYNKKFLSRVYPS 217
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 530418161 1015 GQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08597   218 PMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKF 257
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
940-1054 1.03e-25

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176560 [Multi-domain]  Cd Length: 258  Bit Score: 107.86  E-value: 1.03e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKKialeLSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAKgKKFLQYNRLQLSRIYPKGQRLD 1019
Cdd:cd08623   146 YKILVKNKK----MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSP-VEFVEYNKMQLSRIYPKGTRVD 220
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530418161 1020 SSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08623   221 SSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMY 255
PLN02228 PLN02228
Phosphoinositide phospholipase C
994-1252 3.58e-25

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 112.05  E-value: 3.58e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  994 KAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTMRDEA 1073
Cdd:PLN02228  339 RTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEH 418
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1074 --FDPFDKSSLRGLEPCAISIEVLGARHLPKNGRGIVCP---FVEIEVAGAEYDSTKQKTEFVGQSVFpvillillghck 1148
Cdd:PLN02228  419 tlFDPCKRLPIKTTLKVKIYTGEGWDLDFHLTHFDQYSPpdfFVKIGIAGVPRDTVSYRTETAVDQWF------------ 486
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1149 plptshpilshgdlkpfvvaftvdnglnPVWPAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRA 1228
Cdd:PLN02228  487 ----------------------------PIWGNDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRA 538
                         250       260
                  ....*....|....*....|....
gi 530418161 1229 VPLKNNYSEDLELASLLIKIDIFP 1252
Cdd:PLN02228  539 VRLHDRAGKAYKNTRLLVSFALDP 562
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
940-1054 3.92e-25

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176538 [Multi-domain]  Cd Length: 254  Bit Score: 106.09  E-value: 3.92e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  940 GKIMERRKKiALELSELVVYCRPVPFdeEKIGTERaCYRdMSSFPETKAEKYVNKAKGKkFLQYNRLQLSRIYPKGQRLD 1019
Cdd:cd08596   143 NKILLKNKK-APELSDLVIYCQAVKF--PGLSTPK-CYH-ISSLNENAAKRLCRRYPQK-LVQHTRCQLLRTYPAATRID 216
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530418161 1020 SSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08596   217 SSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMF 251
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
548-645 5.95e-25

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 99.61  E-value: 5.95e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    548 EKWFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDNL 627
Cdd:smart00252    1 QPWYHGFIS-----REEAEKLLK------NEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDG---KFYLEGGR 66
                            90
                    ....*....|....*...
gi 530418161    628 VFDSLYDLITHYQQVPLR 645
Cdd:smart00252   67 KFPSLVELVEHYQKNSLG 84
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
942-1055 3.21e-24

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176537 [Multi-domain]  Cd Length: 257  Bit Score: 103.48  E-value: 3.21e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  942 IMERRKKIALELSELVVYCRPVPFDE-EKIGTERACYRDmSSFPETKAEKYVnKAKGKKFLQYNRLQLSRIYPKGQRLDS 1020
Cdd:cd08595   143 LVKNKKKIAKALSDLVIYTKSEKFCSfTHSRDNQHSYEN-NSIGENKARKLL-KSSGADFVGHTQRFITRIYPKGTRASS 220
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530418161 1021 SNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFM 1055
Cdd:cd08595   221 SNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFL 255
SH2 pfam00017
SH2 domain;
668-741 4.16e-24

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 96.90  E-value: 4.16e-24
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161   668 WYHASLTRAQAEHMLMRVPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLGNSEFDSLVDLISYY 741
Cdd:pfam00017    1 WYHGKISRQEAERLLLNGKPDGTFLVRESeSTPGGYTLSVRDDGKVKHYKIQStdNGGYYISGGVKFSSLAELVEHY 77
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
939-1054 1.25e-23

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 101.66  E-value: 1.25e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  939 EGKIMERRKKIALELSELVVYCRPVPFDEekIGTERACYRDMSSFPETKAEKYVNKaKGKKFLQYNRLQLSRIYPKGQRL 1018
Cdd:cd08633   139 KGKILVKGKKLSRALSDLVKYTKSVRVHD--IETEATSSWQVSSFSETKAHQILQQ-KPAQYLRFNQRQLSRIYPSSYRV 215
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 530418161 1019 DSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08633   216 DSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 251
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
795-849 4.69e-23

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212902  Cd Length: 55  Bit Score: 93.36  E-value: 4.69e-23
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  795 AVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEM 849
Cdd:cd11969     1 TVKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQHYFPSNYVEDV 55
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
979-1055 2.38e-22

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 176536 [Multi-domain]  Cd Length: 227  Bit Score: 97.18  E-value: 2.38e-22
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  979 DMSSFPETKAEKYVNKaKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFM 1055
Cdd:cd08594   150 QVSSFSETRAHQIVQQ-KAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFR 225
PLN02223 PLN02223
phosphoinositide phospholipase C
295-505 4.20e-22

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 102.02  E-value: 4.20e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  295 LDEFVTFLFSKEnsvWNSQL-DAVCPDTMNNPLSHYWISSSHNTYLTGDQ-FSSESSLEAYARCLRMGCRCIELDCW-DG 371
Cdd:PLN02223   83 LDHLNEFLFSTE---LNPPIgDQVRHHDMHAPLSHYFIHTSLKSYFTGNNvFGKLYSIEPIIDALEQGVRVVELDLLpDG 159
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  372 PDGMpVIYHGHTLTTKIKFSDVLHTIKEHAFVASE-YPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVEISADGLP 450
Cdd:PLN02223  160 KDGI-CVRPKWNFEKPLELQECLDAIKEHAFTKCRsYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQHSLEEFP 238
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  451 SPNQLKRKILIKHKKlaegsayeevPTSMMYSeNDISNSI--KNGILYLEDPVNHEW 505
Cdd:PLN02223  239 SPAELQNKILISRRP----------PKELLYA-KADDGGVgvRNELEIQEGPADKNY 284
PLN02222 PLN02222
phosphoinositide phospholipase C 2
985-1249 9.17e-22

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 101.26  E-value: 9.17e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  985 ETKAEKYvnkakGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMTGRHCGYVL 1064
Cdd:PLN02222  353 EKAAEKY-----AKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIK 427
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1065 QP-----STMRDEAFDPfdKSSLrglePCAISIEV---LGA------RHLPKNGRGIVCPFVEIEVAGAEYDSTKQKTEf 1130
Cdd:PLN02222  428 KPdlllkSGSDSDIFDP--KATL----PVKTTLRVtiyMGEgwyfdfRHTHFDQYSPPDFYTRVGIAGVPGDTVMKKTK- 500
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1131 vgqsvfpvillillghckplptshpilshgdlkpfvvafTVDNGLNPVWPaKPFHFQISNPEFAFLRFVVYEEDMFSDQN 1210
Cdd:PLN02222  501 ---------------------------------------TLEDNWIPAWD-EVFEFPLTVPELALLRLEVHEYDMSEKDD 540
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 530418161 1211 FLAQATFPVKGLKTGYRAVPLKNNYSEDLELASLLIKID 1249
Cdd:PLN02222  541 FGGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKVE 579
PLN02952 PLN02952
phosphoinositide phospholipase C
788-1247 1.38e-21

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 100.84  E-value: 1.38e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  788 PMPTFKCaVKALFDYKAQR---------EDELTFIKSAIIQNVEKQEggwwrgdYGGkkQLWFP-SNYVEEMVNPVAL-- 855
Cdd:PLN02952  191 PVPLIKC-LKSIRDYAFSSspypviitlEDHLTPDLQAKVAEMATQI-------FGQ--MLYYPeSDSLVQFPSPESLkh 260
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  856 ------EPEREHLDENSPLGDLLRGvldvpacqiAIRPEGKNNRLFVFSISmaSVAHWSLDVAADSQEELQDWVKKIREV 929
Cdd:PLN02952  261 riiistKPPKEYLESSGPIVIKKKN---------NVSPSGRNSSEETEEAQ--TLESMLFEQEADSRSDSDQDDNKSGEL 329
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  930 AQTADARLTEGKIMERRKKIALELSELVVYCRPVPFDEEKIgtERACyrdmssfpETKAEKYVnkakgkKFLQYNRLqls 1009
Cdd:PLN02952  330 QKPAYKRLITIHAGKPKGTLKDAMKVAVDKVRRLSLSEQEL--EKAA--------TTNGQDVV------RFTQRNIL--- 390
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1010 RIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTM-----RDEAFDPfdKSSLRG 1084
Cdd:PLN02952  391 RIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLmkkgfHDEVFDP--KKKLPV 468
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1085 LEPCAISIEV-----LGARHLPKNGRGIVCPFVEIEVAGAEYDSTKQKTEFvgqsvfpvillillghckplptshpilsh 1159
Cdd:PLN02952  469 KKTLKVKVYLgdgwrLDFSHTHFDSYSPPDFYTKMYIVGVPADNAKKKTKI----------------------------- 519
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1160 gdlkpfvvaftVDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRAVPLKNNYSEDL 1239
Cdd:PLN02952  520 -----------IEDNWYPAW-NEEFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

                  ....*...
gi 530418161 1240 ELASLLIK 1247
Cdd:PLN02952  588 KNVRLLMR 595
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
667-747 1.84e-21

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 89.60  E-value: 1.84e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161    667 EWYHASLTRAQAEHMLMRVPrDGAFLVRK-RNEPNSYAISFRAEGKIKHCRVQQ-EGQTVMLGNSE-FDSLVDLISYYEK 743
Cdd:smart00252    2 PWYHGFISREEAEKLLKNEG-DGDFLVRDsESSPGDYVLSVRVKGKVKHYRIRRnEDGKFYLEGGRkFPSLVELVEHYQK 80

                    ....
gi 530418161    744 HPLY 747
Cdd:smart00252   81 NSLG 84
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
982-1054 2.99e-21

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 176540 [Multi-domain]  Cd Length: 231  Bit Score: 93.85  E-value: 2.99e-21
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161  982 SFPETKAEKYVNKAKgKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08598   157 SLSERSLLKLLKDKR-AALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
333-447 3.53e-20

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.


Pssm-ID: 176498 [Multi-domain]  Cd Length: 179  Bit Score: 89.42  E-value: 3.53e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  333 SSHNTYLTGDQfssESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLT------TKIKFSDVLHTIKEHAFvASE 406
Cdd:cd08555     2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 530418161  407 YPVILSIEDHCSIA----QQRNMAQYFKK-----VLGDTLLTKPVEISAD 447
Cdd:cd08555    78 YTIILSLEIKQDSPeydeFLAKVLKELRVyfdydLRGKVVLSSFNALGVD 127
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
550-639 2.87e-19

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 83.27  E-value: 2.87e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGDYTLSFW-RNGKVQHCRIHSRQDAGTpkFFLTDNLV 628
Cdd:cd00173     2 WFHGSIS-----REEAERLLR------GKPDGTFLVRESSSEPGDYVLSVRsGDGKVKHYLIERNEGGYY--LLGGSGRT 68
                          90
                  ....*....|.
gi 530418161  629 FDSLYDLITHY 639
Cdd:cd00173    69 FPSLPELVEHY 79
PLN02230 PLN02230
phosphoinositide phospholipase C 4
982-1249 3.66e-18

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 90.15  E-value: 3.66e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  982 SFPETKAEKYVnKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMTGRHCG 1061
Cdd:PLN02230  363 SLSEQLLEKAV-ASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCG 441
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1062 YVLQPSTMRD-----EAFDPFDKSSLRGlepcAISIEVLGAR----HLPKNGRGIVCP---FVEIEVAGAEYDSTKQKTE 1129
Cdd:PLN02230  442 YVKKPDFLMDagpngQDFYPKDNSCPKK----TLKVKVCMGDgwllDFKKTHFDSYSPpdfFVRVGIAGAPVDEVMEKTK 517
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1130 FVGQSvfpvillillghckplptshpilshgdlkpfvvaftvdngLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQ 1209
Cdd:PLN02230  518 IEYDT----------------------------------------WTPIW-NKEFIFPLAVPELALLRVEVHEHDINEKD 556
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 530418161 1210 NFLAQATFPVKGLKTGYRAVPLKNNYSEDLELASLLIKID 1249
Cdd:PLN02230  557 DFGGQTCLPVSEIRQGIHAVPLFNRKGVKYSSTRLLMRFE 596
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
796-848 1.20e-17

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 77.74  E-value: 1.20e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTG-WFPSNYVKE 53
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
667-741 2.46e-17

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 77.88  E-value: 2.46e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  667 EWYHASLTRAQAEHMLMRVPrDGAFLVRKR-NEPNSYAISFRAE-GKIKHCRVQQEGQTVMLGNSE---FDSLVDLISYY 741
Cdd:cd00173     1 PWFHGSISREEAERLLRGKP-DGTFLVRESsSEPGDYVLSVRSGdGKVKHYLIERNEGGYYLLGGSgrtFPSLPELVEHY 79
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
796-847 3.55e-17

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 76.42  E-value: 3.55e-17
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 530418161    796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:smart00326    5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
666-747 7.21e-16

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 74.09  E-value: 7.21e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  666 KEWYHASLTRAQAEHMLMRVPRDGAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISYYEKH 744
Cdd:cd09943     1 QPWYYGRITRHQAETLLNEHGHEGDFLIRdSESNPGDYSVSLKAPGRNKHFKVQVVDNVYCIGQRKFHTMDELVEHYKKA 80

                  ...
gi 530418161  745 PLY 747
Cdd:cd09943    81 PIF 83
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
796-848 8.08e-16

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 72.45  E-value: 8.08e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11840     2 VIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGL-FPSNYVEP 53
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
548-641 1.28e-15

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 73.77  E-value: 1.28e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLS-----FWRNGKVQHCRIHSRQDAGtpkFF 622
Cdd:cd09933     3 EEWFFGKIK-----RKDAEKLL----LAPGNPRGTFLIRESETTPGAYSLSvrdgdDARGDTVKHYRIRKLDNGG---YY 70
                          90
                  ....*....|....*....
gi 530418161  623 LTDNLVFDSLYDLITHYQQ 641
Cdd:cd09933    71 ITTRATFPTLQELVQHYSK 89
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
489-523 1.33e-15

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270054  Cd Length: 105  Bit Score: 73.66  E-value: 1.33e-15
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 530418161  489 SIKNGILYLEDPVNHEWYPHYFVLTSSKIYYSEET 523
Cdd:cd13234     1 SIKNGILYLEDPINHEWYPHFFVLTSNKIYYSEET 35
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
797-843 1.54e-15

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 71.47  E-value: 1.54e-15
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 530418161   797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPS 843
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
793-848 2.33e-15

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700  Cd Length: 53  Bit Score: 71.14  E-value: 2.33e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  793 KCAVKalFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11766     1 PAVVK--FNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVG-WFPSNYVTE 53
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
796-848 3.06e-15

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 70.76  E-value: 3.06e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11873     2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGM-FPDNFVKV 53
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
550-640 3.65e-15

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 72.32  E-value: 3.65e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDagtpKFFLTDNLVF 629
Cdd:cd09937     5 WFHGKIS-----REEAERLLQP------PEDGLFLVRESTNYPGDYTLCVSFEGKVEHYRVIYRNG----KLTIDEEEYF 69
                          90
                  ....*....|.
gi 530418161  630 DSLYDLITHYQ 640
Cdd:cd09937    70 ENLIQLVEHYT 80
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
796-845 3.73e-15

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 70.57  E-value: 3.73e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNY 845
Cdd:cd00174     2 ARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGREGLFPANY 51
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
980-1054 4.83e-15

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 75.87  E-value: 4.83e-15
                          10        20        30        40        50        60        70
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gi 530418161  980 MSSFPETKAEKYVNKAKGKKFLQYNRLQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd08599   151 RNSLSETQLKKVIEGEHPTDLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKF 225
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
48-142 8.95e-15

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 270170  Cd Length: 109  Bit Score: 71.54  E-value: 8.95e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   48 RKTFQVKLETRQITW---SRGADKieGAIDIREIKEIRPGKTSRDFDRYQEDPAFRPDqsHCFVILYGMEFrlKTLSLQA 124
Cdd:cd13364    18 RRFFYLDEDKSSIRWkpsKKKSEK--AKIPISSIREVREGKTTDIFRSCDISGDFPEE--CCFSIIYGEEY--ETLDLVA 91
                          90
                  ....*....|....*...
gi 530418161  125 TSEDEVNMWIKGLTWLME 142
Cdd:cd13364    92 SSPDEANIWITGLRYLMS 109
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
549-639 9.00e-15

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 70.53  E-value: 9.00e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  549 KWFHGKLGagrdgRHIAERLLTeycieTGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRqdaGTPKFFLTDnLV 628
Cdd:cd10354     1 IWFHGKIS-----REEAYNMLV-----KVGGPGSFLVRESDNTPGDYSLSFRVNEGIKHFKIIPT---GNNQFMMGG-RY 66
                          90
                  ....*....|.
gi 530418161  629 FDSLYDLITHY 639
Cdd:cd10354    67 FSSLDDVIDRY 77
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
667-741 9.00e-15

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 70.53  E-value: 9.00e-15
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  667 EWYHASLTRAQAEHMLMRVPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRV-QQEGQTVMLGNSEFDSLVDLISYY 741
Cdd:cd10354     1 IWFHGKISREEAYNMLVKVGGPGSFLVRESdNTPGDYSLSFRVNEGIKHFKIiPTGNNQFMMGGRYFSSLDDVIDRY 77
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
668-757 9.63e-15

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 71.16  E-value: 9.63e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPRDGAFLVRK-RNEPNSYAISFRA-EGKIKHCRVQ-QEGQTVMLGNSEFDSLVDLISYYEKH 744
Cdd:cd09931     2 WFHGHLSGKEAEKLLLEKGKPGSFLVREsQSKPGDFVLSVRTdDDKVTHIMIRcQGGKYDVGGGEEFDSLTDLVEHYKKN 81
                          90
                  ....*....|....*..
gi 530418161  745 PLY----RKMKLRYPIN 757
Cdd:cd09931    82 PMVetsgTVVHLKQPLN 98
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
666-747 1.08e-14

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 70.83  E-value: 1.08e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  666 KEWYHASLTRAQAEHMLMRVPRDGAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISYYEKH 744
Cdd:cd10408     1 NPWYYGKVTRHQAEMALNERGNEGDFLIRdSESSPNDFSVSLKAQGKNKHFKVQLKECVYCIGQRKFSSMEELVEHYKKA 80

                  ...
gi 530418161  745 PLY 747
Cdd:cd10408    81 PIF 83
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
664-756 1.88e-14

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 70.51  E-value: 1.88e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISF----RAEGKIKHCRVQQ--EGQTVMLGNSEFDSLVDL 737
Cdd:cd09934     4 EKYEWYVGDMSRQRAESLLKQEDKEGCFVVRNSSTKGLYTVSLftkvPGSPHVKHYHIKQnaRSEFYLAEKHCFETIPEL 83
                          90
                  ....*....|....*....
gi 530418161  738 ISYYEKHPLYRKMKLRYPI 756
Cdd:cd09934    84 INYHQHNSGGLATRLKYPV 102
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
548-639 2.89e-14

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 68.94  E-value: 2.89e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLTEycieTGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIhsRQDAGTPKFFLTDNL 627
Cdd:cd10347     1 LRWYHGKIS-----REVAEALLLR----EGGRDGLFLVRESTSAPGDYVLSLLAQGEVLHYQI--RRHGEDAFFSDDGPL 69
                          90
                  ....*....|..
gi 530418161  628 VFDSLYDLITHY 639
Cdd:cd10347    70 IFHGLDTLIEHY 81
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
666-746 3.18e-14

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 69.63  E-value: 3.18e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  666 KEWYHASLTRAQAEHMLMRVPrDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLGNSEFDSLVDLISYYE 742
Cdd:cd09940     5 FLWFVGEMERDTAENRLENRP-DGTYLVRVRpQGETQYALSIKYNGDVKHMKIEQrsDGLYYLSESRHFKSLVELVNYYE 83

                  ....
gi 530418161  743 KHPL 746
Cdd:cd09940    84 RNSL 87
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
664-746 5.17e-14

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 68.66  E-value: 5.17e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRNE-PNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISYYE 742
Cdd:cd10355     4 QSLGWYHGNLTRHAAEALLLSNGVDGSYLLRNSNEgTGLFSLSVRAKDSVKHFHVEYTGYSFKFGFNEFSSLQDFVKHFA 83

                  ....
gi 530418161  743 KHPL 746
Cdd:cd10355    84 NQPL 87
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
550-643 6.94e-14

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 68.57  E-value: 6.94e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDNLVF 629
Cdd:cd09935     5 WYHGPIS-----RNAAEYLLSS------GINGSFLVRESESSPGQYSISLRYDGRVYHYRISEDSDG---KVYVTQEHRF 70
                          90
                  ....*....|....
gi 530418161  630 DSLYDLITHYQQVP 643
Cdd:cd09935    71 NTLAELVHHHSKNA 84
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
666-747 7.37e-14

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 68.52  E-value: 7.37e-14
                          10        20        30        40        50        60        70        80
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gi 530418161  666 KEWYHASLTRAQAEHMLMRVPRDGAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISYYEKH 744
Cdd:cd10409     1 KEWYYGNVTRHQAECALNERGVEGDFLIRdSESSPSDFSVSLKAVGKNKHFKVQLVDNVYCIGQRRFNSMDELVEHYKKA 80

                  ...
gi 530418161  745 PLY 747
Cdd:cd10409    81 PIF 83
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
797-848 1.93e-13

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 65.83  E-value: 1.93e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11823     3 KALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGI-FPATYVEE 53
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
800-848 4.08e-13

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 64.92  E-value: 4.08e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  800 FDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd12052     6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGL-FPDNFVRE 53
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
796-849 4.31e-13

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 65.02  E-value: 4.31e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEEM 849
Cdd:cd12060     4 VKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTG-WFPSNYVREI 56
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1090-1231 6.32e-13

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 65.97  E-value: 6.32e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   1090 ISIEVLGARHLP-KNGRGIVCPFVEIEVAGAeyDSTKQKTEfvgqsvfpvillillghckplptshpilshgdlkpfvva 1168
Cdd:smart00239    2 LTVKIISARNLPpKDKGGKSDPYVKVSLDGD--PKEKKKTK--------------------------------------- 40
                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161   1169 fTVDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRAVPL 1231
Cdd:smart00239   41 -VVKNTLNPVW-NETFEFEVPPPELAELEIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRHEKL 101
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
664-755 6.46e-13

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 65.87  E-value: 6.46e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLmRVPRDGAFLVRK-RNEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLGNSEFDSLVDLISY 740
Cdd:cd09935     1 EKHSWYHGPISRNAAEYLL-SSGINGSFLVREsESSPGQYSISLRYDGRVYHYRISEdsDGKVYVTQEHRFNTLAELVHH 79
                          90
                  ....*....|....*
gi 530418161  741 YEKHPLYRKMKLRYP 755
Cdd:cd09935    80 HSKNADGLITTLRYP 94
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
800-848 7.43e-13

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212834  Cd Length: 55  Bit Score: 64.29  E-value: 7.43e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  800 FDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11901     8 FNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVG-WFPSNYVTE 55
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
796-849 9.65e-13

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 63.94  E-value: 9.65e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEEM 849
Cdd:cd12061     2 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTG-WFPSNYVREI 54
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
796-848 9.77e-13

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212706 [Multi-domain]  Cd Length: 53  Bit Score: 63.86  E-value: 9.77e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11772     2 FRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGL-IPSNYVEE 53
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
549-644 1.14e-12

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 65.38  E-value: 1.14e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  549 KWFHGKLgAGRDgrhiAERLLTEycietGAPDGSFLVRESETFVGDYTLSFWRN-GKVQHCRIHSRQDagtpKFFLTDNL 627
Cdd:cd09931     1 RWFHGHL-SGKE----AEKLLLE-----KGKPGSFLVRESQSKPGDFVLSVRTDdDKVTHIMIRCQGG----KYDVGGGE 66
                          90
                  ....*....|....*..
gi 530418161  628 VFDSLYDLITHYQQVPL 644
Cdd:cd09931    67 EFDSLTDLVEHYKKNPM 83
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
934-1054 1.45e-12

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176497 [Multi-domain]  Cd Length: 274  Bit Score: 69.60  E-value: 1.45e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  934 DARlteGKIMERRKKiaLELSELVVYCRPVPFDEEKIGTERACYRDMSSFPETKA---EKYVNKAKGKKFLQYNRLQLSR 1010
Cdd:cd00137   141 DLR---GKILLLNKK--NGFSGPTGSSNDTGFVSFEFSTQKNRSYNISSQDEYKAyddEKVKLIKATVQFVDYNKNQLSR 215
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161 1011 IYPKGQRL---------DSSNYDPLPMW---ICGSQLVALNFQTPDKPMQMNQALF 1054
Cdd:cd00137   216 NYPSGTSGgtawyyyamDSNNYMPQMFWnanPAGCGIVILDFQTMDLPMQQYMAVI 271
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
796-847 1.53e-12

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 63.11  E-value: 1.53e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11826     2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGL-FPGNYVE 52
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
796-848 1.93e-12

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 62.82  E-value: 1.93e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11827     2 CKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGL-FPGNYVEK 53
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
796-848 2.86e-12

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212894 [Multi-domain]  Cd Length: 53  Bit Score: 62.54  E-value: 2.86e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGL-FPSNYVEL 53
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
797-847 3.02e-12

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 62.33  E-value: 3.02e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:cd11819     3 KALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLGVNAKGQKGLFPANYVE 53
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
796-848 4.51e-12

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212696  Cd Length: 57  Bit Score: 62.03  E-value: 4.51e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEG----GWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11762     2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNgvddGWWEGEFNGRVGV-FPSLVVEE 57
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
664-756 4.65e-12

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 63.81  E-value: 4.65e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISF--RA----EGKIKHCRVQQE--GQTVMLGNSEFDSLV 735
Cdd:cd10398     4 EIYEWYHKNITRNQAERLLRQESKEGAFIVRDSRHLGSYTISVftRArrstEASIKHYQIKKNdsGQWYVAERHLFQSIP 83
                          90       100
                  ....*....|....*....|.
gi 530418161  736 DLISYYEKHPLYRKMKLRYPI 756
Cdd:cd10398    84 ELIQYHQHNAAGLMSRLRYPV 104
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
548-642 6.73e-12

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 63.00  E-value: 6.73e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSF--W---RNGKVQHCRIHSRQDAGtpkFF 622
Cdd:cd10367     3 EEWYFGKIG-----RKDAERQL----LSPGNPRGAFLIRESETTKGAYSLSIrdWdqnRGDHVKHYKIRKLDTGG---YY 70
                          90       100
                  ....*....|....*....|
gi 530418161  623 LTDNLVFDSLYDLITHYQQV 642
Cdd:cd10367    71 ITTRAQFDTVQELVQHYMEV 90
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
665-756 6.74e-12

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 63.87  E-value: 6.74e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  665 SKEWYHASLTRAQAEHMLMRVPRDGAFLVR---KRNEPNSYAISFRAEGKIKH--CRVQQEGQTVMLGN----SE-FDSL 734
Cdd:cd09929    10 PKEWYAGNIDRKEAEEALRRSNKDGTFLVRdssGKDSSQPYTLMVLYNDKVYNiqIRFLENTRQYALGTglrgEEtFSSV 89
                          90       100       110
                  ....*....|....*....|....*....|.
gi 530418161  735 VDLISYYEKHPLY---------RKMKLRYPI 756
Cdd:cd09929    90 AEIIEHHQKTPLLlidgkdntkDSTCLLYAA 120
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
797-847 7.50e-12

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212892 [Multi-domain]  Cd Length: 53  Bit Score: 61.28  E-value: 7.50e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11959     3 VALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGL-FPANYVE 52
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
548-639 9.48e-12

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 62.71  E-value: 9.48e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSF--WRNGK---VQHCRIHSRQDAGtpkFF 622
Cdd:cd10418     3 EEWYFGKLG-----RKDAERQL----LSFGNPRGTFLIRESETTKGAYSLSIrdWDDMKgdhVKHYKIRKLDNGG---YY 70
                          90
                  ....*....|....*..
gi 530418161  623 LTDNLVFDSLYDLITHY 639
Cdd:cd10418    71 ITTRAQFETLQQLVQHY 87
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
548-641 1.25e-11

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 62.35  E-value: 1.25e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLTEYcietGAPDGSFLVRESETFVGDYTLSF--WRNGK---VQHCRIHSRQDAGtpkFF 622
Cdd:cd10368     3 EEWYFGKLG-----RKDAERQLLSF----GNPRGTFLIRESETTKGAYSLSIrdWDDMKgdhVKHYKIRKLDNGG---YY 70
                          90
                  ....*....|....*....
gi 530418161  623 LTDNLVFDSLYDLITHYQQ 641
Cdd:cd10368    71 ITTRAQFETLQQLVQHYSE 89
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
800-848 1.42e-11

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212835  Cd Length: 55  Bit Score: 60.79  E-value: 1.42e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  800 FDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11902     7 FAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIG-WFPSNYVVE 54
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
668-743 1.96e-11

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 61.54  E-value: 1.96e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  668 WYHASLTRAQAEHMLmRVPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSE-FDSLVDLISYYEK 743
Cdd:cd09937     5 WFHGKISREEAERLL-QPPEDGLFLVREStNYPGDYTLCVSFEGKVEHYRVIYRNGKLTIDEEEyFENLIQLVEHYTK 81
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
660-745 3.04e-11

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 61.48  E-value: 3.04e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  660 TNAHESKEWYHASLTRAQAEHMLMRVPR-DGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQE--GQTVMLGNSEFDSLVD 736
Cdd:cd10402     4 TTAHERMPWYHGSIARDEAERRLYSGAQpDGKFLLRERKESGTYALSLVYGKTVYHYRIDQDksGKYSIPEGTKFDTLWQ 83

                  ....*....
gi 530418161  737 LISYYEKHP 745
Cdd:cd10402    84 LVEYLKLKP 92
C2 pfam00168
C2 domain;
1090-1228 4.59e-11

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 60.80  E-value: 4.59e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  1090 ISIEVLGARHLP-KNGRGIVCPFVEIEVAGaeyDSTKQKTEfvgqsvfpvillillghckplptshpilshgdlkpfvva 1168
Cdd:pfam00168    3 LTVTVIEAKNLPpKDGNGTSDPYVKVYLLD---GKQKKKTK--------------------------------------- 40
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  1169 fTVDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRA 1228
Cdd:pfam00168   41 -VVKNTLNPVW-NETFTFSVPDPENAVLEIEVYDYDRFGRDDFIGEVRIPLSELDSGEGL 98
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
544-640 4.71e-11

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197  Cd Length: 108  Bit Score: 60.90  E-value: 4.71e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  544 LHSNEKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFL 623
Cdd:cd09944     1 IHRSQPWFHGGIS-----RDEAARLI----RQQGLVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIIPIEDEGQWYFTL 71
                          90
                  ....*....|....*...
gi 530418161  624 TD-NLVFDSLYDLITHYQ 640
Cdd:cd09944    72 DDgVTKFYDLLQLVEFYQ 89
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
156-306 6.49e-11

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 61.53  E-value: 6.49e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVPNmRFLRERLTDLEQ-RSGDITYGQFAQLYRSLMysAQKTMDLPFLE 234
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSE-KELKKLFKEVDTnGDGTLTFDEFEELYKSLT--ERPELEPIFKK 77
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161  235 -ASTLRAGerpelcrVSLPEFQQFLLDYQGElwAVDRLQVQEFMLSFLRDPlreiEEPYFFLDEFVTFLFSKE 306
Cdd:cd15898    78 yAGTNRDY-------MTLEEFIRFLREEQGE--NVSEEECEELIEKYEPER----ENRQLSFEGFTNFLLSPE 137
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
576-657 6.98e-11

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 60.42  E-value: 6.98e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  576 TGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDagtpKFFLTDNLVFDSLYDLITHYQQVPLR-CN-EFEMRL 653
Cdd:cd09942    24 RDTPDGTFLVRDASTMKGDYTLTLRKGGNNKLIKIFHRDG----KYGFSDPLTFNSVVELINYYRNNSLAeYNrKLDVKL 99

                  ....
gi 530418161  654 SEPV 657
Cdd:cd09942   100 LYPV 103
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
663-757 7.94e-11

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 60.12  E-value: 7.94e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLmRVPRDGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQEGQTvmLGNSE----FDSLVDLI 738
Cdd:cd09930     3 HDERTWLVGDINRTQAEELL-RGKPDGTFLIRESSTQGCYACSVVCNGEVKHCVIYKTETG--YGFAEpynlYESLKELV 79
                          90       100
                  ....*....|....*....|....
gi 530418161  739 SYY-----EKHPLYRKMKLRYPIN 757
Cdd:cd09930    80 LHYahnslEQHNDSLTVTLAYPVL 103
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
668-756 1.01e-10

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 59.75  E-value: 1.01e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLmRVPRDGAFLVRK-RNEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLGNSE-FDSLVDLISYYEK 743
Cdd:cd09945     3 WYHGAITRIEAESLL-RPCKEGSYLVRNsESTKQDYSLSLKSAKGFMHMRIQRneTGQYILGQFSRpFETIPEMIRHYCL 81
                          90
                  ....*....|....*..
gi 530418161  744 HPLYRK----MKLRYPI 756
Cdd:cd09945    82 NKLPVRgaehMCLLEPV 98
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
650-741 1.47e-10

N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198216  Cd Length: 103  Bit Score: 59.46  E-value: 1.47e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  650 EMRLSEPVPQTNAHESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRN-EPNSYAISFRAEGKIKHCRVQQEGQTVMLGN 728
Cdd:cd10353     3 EYEEEEVAIPLTAPPTNQWYHGRLDRTIAEERLRQAGKLGSYLIRESDrRPGSFVLSFLSRTGVNHFRIIAMCGDYYIGG 82
                          90
                  ....*....|...
gi 530418161  729 SEFDSLVDLISYY 741
Cdd:cd10353    83 RRFSSLSDLIGYY 95
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
796-848 1.54e-10

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 57.75  E-value: 1.54e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEK--QEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKdcEDKGWWKGELNGKRGV-FPDNFVEP 55
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
796-847 2.00e-10

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 57.41  E-value: 2.00e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:cd11960     2 ARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGTGPDGTYGLFPANYVE 53
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
794-847 2.09e-10

Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212929 [Multi-domain]  Cd Length: 54  Bit Score: 57.30  E-value: 2.09e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  794 CAVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11996     1 CQVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGL-FPSNYVK 53
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
793-848 2.19e-10

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 57.34  E-value: 2.19e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  793 KCavKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11874     1 RC--KVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGV-FPSNFVKE 53
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
668-757 2.39e-10

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 58.56  E-value: 2.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPRDGAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQEGQTVML-GNSEFDSLVDLISYYEKHP 745
Cdd:cd10340     2 WFHPVISGIEAENLLKTRGVDGSFLARpSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLyGGEKFATLSELVQYYMEQH 81
                          90
                  ....*....|....*...
gi 530418161  746 --LYRK----MKLRYPIN 757
Cdd:cd10340    82 gqLREKngdvIELKYPLN 99
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
794-847 2.86e-10

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212928 [Multi-domain]  Cd Length: 54  Bit Score: 56.89  E-value: 2.86e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  794 CAVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11995     1 CQVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGL-FPSNYVK 53
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
545-644 3.59e-10

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 58.19  E-value: 3.59e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  545 HSNEK-WFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETfVGDYTLSFWRNGKVQHCRIhsRQDAGTPKFFL 623
Cdd:cd09930     2 HHDERtWLVGDIN-----RTQAEELLR------GKPDGTFLIRESST-QGCYACSVVCNGEVKHCVI--YKTETGYGFAE 67
                          90       100
                  ....*....|....*....|.
gi 530418161  624 TDNLvFDSLYDLITHYQQVPL 644
Cdd:cd09930    68 PYNL-YESLKELVLHYAHNSL 87
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
797-849 3.86e-10

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 56.51  E-value: 3.86e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEEM 849
Cdd:cd12054     4 KVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGL-FPSNFVKEL 55
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
549-642 3.97e-10

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 58.27  E-value: 3.97e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  549 KWFHGKLGAGRdGRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSFWRNG-----KVQHCRIHSRQDAGtpkFFL 623
Cdd:cd10344     7 KVYHGWLFEGL-SREKAEELL----MLPGNQVGSFLIRESETRRGCYSLSVRHRGsqsrdSVKHYRIFRLDNGW---FYI 78
                          90
                  ....*....|....*....
gi 530418161  624 TDNLVFDSLYDLITHYQQV 642
Cdd:cd10344    79 SPRLTFQCLEDMVNHYSES 97
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
661-756 4.50e-10

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260  Cd Length: 106  Bit Score: 57.92  E-value: 4.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  661 NAHESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISFRAE------GKIKH---CRVQQeGQTVMLGNSEF 731
Cdd:cd10397     1 DSLEMYEWYSKNMTRSQAEQLLKQEGKEGGFIVRDSSKAGKYTVSVFAKsagdpqGVIRHyvvCSTPQ-SQYYLAEKHLF 79
                          90       100
                  ....*....|....*....|....*
gi 530418161  732 DSLVDLISYYEKHPLYRKMKLRYPI 756
Cdd:cd10397    80 STIPELINYHQHNAAGLISRLKYPV 104
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
668-741 5.41e-10

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 57.00  E-value: 5.41e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530418161  668 WYHASLTRAQAEHMLMRV-PRDGAFLVRK-RNEPNSYAISFRAEGKIKHCRVQQEGQ---TVMLGNSEFDSLVDLISYY 741
Cdd:cd10347     3 WYHGKISREVAEALLLREgGRDGLFLVREsTSAPGDYVLSLLAQGEVLHYQIRRHGEdafFSDDGPLIFHGLDTLIEHY 81
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
550-641 7.21e-10

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 56.89  E-value: 7.21e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIhSRQDAGtpKFFLTDNlVF 629
Cdd:cd09941     5 WFHGKIS-----RAEAEEILMN-----QRPDGAFLIRESESSPGDFSLSVKFGNDVQHFKV-LRDGAG--KYFLWVV-KF 70
                          90
                  ....*....|..
gi 530418161  630 DSLYDLITHYQQ 641
Cdd:cd09941    71 NSLNELVDYHRT 82
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
668-755 7.94e-10

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 57.38  E-value: 7.94e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLmRVPRDGAFLVRKRN-EPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSE-FDSLVDLISYYEKHP 745
Cdd:cd10406     7 WFAGNMERQQTDNLL-KSHASGTYLIRERPaEAERFAISIKFNDEVKHIKVVEKDNWIHITEAKkFESLLELVEYYQCHS 85
                          90
                  ....*....|....*
gi 530418161  746 LYRKMK-----LRYP 755
Cdd:cd10406    86 LKESFKqldttLKYP 100
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
796-846 8.18e-10

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 55.59  E-value: 8.18e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYV 846
Cdd:cd11812     2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLVNGQQGYFPANYV 52
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
20-141 8.82e-10

Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the second class of PLC discovered. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). This cd contains PLC members from fungi and plants. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270171  Cd Length: 115  Bit Score: 57.29  E-value: 8.82e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   20 AEVLHLCRSLEVGTVMtLFYSKKSqRPERKTFQVKLETRQITWSRGADKIEGAIDIREIKEIRPGKTSRDFDRYQEDPAF 99
Cdd:cd13365     1 RDVIEAITQLKIGSYL-LKYGRRG-KPHFRYFWLSPDELTLYWSSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPPPPGLE 78
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 530418161  100 rpdqSHCFVILYGMEFRlkTLSLQATSEDEVNMWIKGLTWLM 141
Cdd:cd13365    79 ----EHSFSIIYADGER--SLDLTCKDRQEFDTWFTGLRYLL 114
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
668-748 1.01e-09

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 56.51  E-value: 1.01e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPRDGAFLVRK-RNEPNSYAISFRAEGKIKHCRVQQEGQtvmlGN-----SEFDSLVDLISYY 741
Cdd:cd09941     5 WFHGKISRAEAEEILMNQRPDGAFLIREsESSPGDFSLSVKFGNDVQHFKVLRDGA----GKyflwvVKFNSLNELVDYH 80

                  ....*..
gi 530418161  742 EKHPLYR 748
Cdd:cd09941    81 RTTSVSR 87
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
548-640 1.35e-09

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 56.36  E-value: 1.35e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGtpkFFLTDNL 627
Cdd:cd10370     3 EPWYFGKIK-----RIEAEKKL----LLPENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRQLDEGG---FFIARRT 70
                          90
                  ....*....|...
gi 530418161  628 VFDSLYDLITHYQ 640
Cdd:cd10370    71 TFRTLQELVEHYS 83
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
546-641 1.44e-09

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 56.61  E-value: 1.44e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  546 SNEKWFHGKLGagrdgRHIAERLLTEYcietGAPDGSFLVRESETFVGDYTLSF--WRNGKVQHCRIHSRQDAGTPKFFL 623
Cdd:cd10419     1 QAEEWYFGKLG-----RKDAERQLLSF----GNPRGTFLIRESETTKGAYSLSIrdWDDMKGDHVKHYKIRKLDNGGYYI 71
                          90
                  ....*....|....*...
gi 530418161  624 TDNLVFDSLYDLITHYQQ 641
Cdd:cd10419    72 TTRAQFETLQQLVQHYSE 89
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
548-639 1.53e-09

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 56.04  E-value: 1.53e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGtpkFFLTDNL 627
Cdd:cd10369     3 EPWFFGAIK-----RADAEKQL----LYSENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIRRLDEGG---FFLTRRK 70
                          90
                  ....*....|..
gi 530418161  628 VFDSLYDLITHY 639
Cdd:cd10369    71 TFSTLNEFVNYY 82
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
550-653 1.56e-09

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 55.98  E-value: 1.56e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEYCIEtgapdGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQdagtpKFFLTDNLVF 629
Cdd:cd09943     3 WYYGRIT-----RHQAETLLNEHGHE-----GDFLIRDSESNPGDYSVSLKAPGRNKHFKVQVVD-----NVYCIGQRKF 67
                          90       100
                  ....*....|....*....|....
gi 530418161  630 DSLYDLITHYQQVPLRCNEFEMRL 653
Cdd:cd09943    68 HTMDELVEHYKKAPIFTSEQGEKL 91
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
796-847 2.17e-09

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212815 [Multi-domain]  Cd Length: 54  Bit Score: 54.22  E-value: 2.17e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNV-EKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11882     2 ARALYACKAEDESELSFEPGQIITNVqPSDEPGWLEGTLNGRTGL-IPENYVE 53
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
546-646 2.34e-09

Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198209  Cd Length: 97  Bit Score: 55.89  E-value: 2.34e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  546 SNEKWFHGKLGagrdgRHIAERLLTEycietGAPD--GSFLVRESETFVGDYTLSFWRNGKVQHCRIhSRQDAGTPKffl 623
Cdd:cd10346     6 SEYPWFHGTLS-----RSDAAQLVLH-----SGADghGVFLVRQSETRRGEFVLTFNFQGRAKHLRL-TLNEKGQCR--- 71
                          90       100
                  ....*....|....*....|....*
gi 530418161  624 TDNLVFDSLYDLITHYQQ--VPLRC 646
Cdd:cd10346    72 VQHLWFPSIFDMLEHFRQnpIPLES 96
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
548-641 2.68e-09

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 55.83  E-value: 2.68e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSF--WRNGK---VQHCRIHSRQDAGtpkFF 622
Cdd:cd10365     3 EEWYFGKIT-----RRESERLL----LNAENPRGTFLVRESETTKGAYCLSVsdFDNAKglnVKHYKIRKLDSGG---FY 70
                          90
                  ....*....|....*....
gi 530418161  623 LTDNLVFDSLYDLITHYQQ 641
Cdd:cd10365    71 ITSRTQFNSLQQLVAYYSK 89
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
794-847 3.91e-09

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 53.68  E-value: 3.91e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  794 CAVkALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd12073     2 CAV-ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGL-FPANYVE 53
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
797-848 4.14e-09

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 53.54  E-value: 4.14e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG-DYGGKKQLWFPSNYVEE 848
Cdd:cd11858     3 KALYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAkKLDESKEGWVPAAYLEE 55
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
664-744 4.18e-09

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 55.28  E-value: 4.18e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLM--RVPRdGAFLVRKR-NEPNSYAISFR-----AEGKIKHCRVQQ--EGQTVMLGNSEFDS 733
Cdd:cd09933     1 EAEEWFFGKIKRKDAEKLLLapGNPR-GTFLIRESeTTPGAYSLSVRdgddaRGDTVKHYRIRKldNGGYYITTRATFPT 79
                          90
                  ....*....|.
gi 530418161  734 LVDLISYYEKH 744
Cdd:cd09933    80 LQELVQHYSKD 90
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
668-740 4.50e-09

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 55.04  E-value: 4.50e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418161  668 WYHASLTRAQAEHMLMrvpRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLISY 740
Cdd:cd09925     9 WYHGKMSRRDAESLLQ---TDGDFLVREStTTPGQYVLTGMQNGQPKHLLLVDPEGVVRTKDRVFESISHLINY 79
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
662-744 4.66e-09

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 54.46  E-value: 4.66e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  662 AHESKEWYHASLTRAQAEHMLMRvprDGAFLVRKRN----EPNSYAISFRAEGKIKH--CRVQQEGQTVMLGNSeFDSLV 735
Cdd:cd10361     2 DLENEPYYHGLLPREDAEELLKN---DGDFLVRKTEpkggGKRKLVLSVRWDGKIRHfvINRDDGGKYYIEGKS-FKSIS 77

                  ....*....
gi 530418161  736 DLISYYEKH 744
Cdd:cd10361    78 ELINYYQKT 86
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
551-637 4.80e-09

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 54.68  E-value: 4.80e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  551 FHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSrqDAGTPKFFLTDnLVFD 630
Cdd:cd10352     9 YHGLIS-----REEAEQLLS------GASDGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYY--DGKNHYHYVGE-KRFD 74

                  ....*..
gi 530418161  631 SLYDLIT 637
Cdd:cd10352    75 TIHDLVA 81
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
795-847 6.40e-09

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212882 [Multi-domain]  Cd Length: 53  Bit Score: 52.92  E-value: 6.40e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  795 AVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11949     1 YVQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGM-FPRNYVT 52
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
668-757 6.50e-09

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 54.96  E-value: 6.50e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISFRA------EGKIKHCRVQQ--EGQTVMLGNSEFDSLVDLIS 739
Cdd:cd10399     8 WFAGNISRSQSEQLLRQKGKEGAFMVRNSSQVGMYTVSLFSkavndkKGTVKHYHVHTnaENKLYLAENYCFDSIPKLIH 87
                          90
                  ....*....|....*...
gi 530418161  740 YYEKHPLYRKMKLRYPIN 757
Cdd:cd10399    88 YHQHNSAGMITRLRHPVS 105
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
325-461 6.66e-09

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar proteins; This subfamily corresponds to the catalytic domain present in bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13) and their sequence homologs found in eukaryota. Bacterial PI-PLCs participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. Bacterial PI-PLCs contain a single TIM-barrel type catalytic domain. Its catalytic mechanism is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. Eukaryotic homologs in this family are named as phosphatidylinositol-specific phospholipase C X domain containing proteins (PI-PLCXD). They are distinct from the typical eukaryotic phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11), which have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. The catalytic core domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. In contrast, eukaryotic PI-PLCXDs contain a single TIM-barrel type catalytic domain, X domain, which is closely related to that of bacterial PI-PLCs. Although the biological function of eukaryotic PI-PLCXDs still remains unclear, it may be distinct from that of typical eukaryotic PI-PLCs. This family also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host's immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176500 [Multi-domain]  Cd Length: 271  Bit Score: 58.64  E-value: 6.66e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  325 PLSHYWISSSHNTY-LTGDQFSSESSleAYARC--------LRMGCRCIELDCWDGPDGMPV-IYHGHTLTTKIKFSDVL 394
Cdd:cd08557     8 PLSQLSIPGTHNSYaYTIDGNSPIVS--KWSKTqdlsitdqLDAGVRYLDLRVAYDPDDGDLyVCHGLFLLNGQTLEDVL 85
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418161  395 HTIKehAFVA---SEyPVILSIEDHCSIAQQRNMA---QYFKKVLGDTLLTKPVeiSADGLPSPNQLKR-KILI 461
Cdd:cd08557    86 NEVK--DFLDahpSE-VVILDLEHEYGGDNGEDHDeldALLRDVLGDPLYRPPV--RAGGWPTLGELRAgKRVL 154
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
795-848 7.54e-09

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771  Cd Length: 53  Bit Score: 52.75  E-value: 7.54e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  795 AVKALFDYKAQREDELTFIKSAIIQNVEKQEgGWWRGDYGGKKQLWFPSNYVEE 848
Cdd:cd11837     1 TATALYPWRAKKENHLSFAKGDIITVLEQQE-MWWFGELEGGEEGWFPKSYVKE 53
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
663-758 7.93e-09

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 54.63  E-value: 7.93e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLM-RVprDGAFLVRKRN-EPNSYAISFRAEGKIKHCRV-QQEGQTVMLGNSEFDSLVDLIS 739
Cdd:cd10407     2 YSCQPWYAGAMERLQAETELInRV--NSTYLVRHRTkESGEYAISIKYNNEVKHIKIlTRDGFFHIAENRKFKSLMELVE 79
                          90       100
                  ....*....|....*....|....
gi 530418161  740 YYEKHPL---YRKM--KLRYPINE 758
Cdd:cd10407    80 YYKHHSLkegFRSLdtTLQFPYKE 103
SH3_9 pfam14604
Variant SH3 domain;
798-847 1.39e-08

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 51.85  E-value: 1.39e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 530418161   798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:pfam14604    1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTGL-VPANYVE 49
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
796-852 1.40e-08

Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It regulates actin cytoskeletal reorganization at adherens junctions and dendritic spines, which is important in cell morphogenesis, migration, and cognitive function. Mice deficient with Abi2 show defects in orientation and migration of lens fibers, neuronal migration, dendritic spine morphology, as well as deficits in learning and memory. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212905 [Multi-domain]  Cd Length: 61  Bit Score: 52.32  E-value: 1.40e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEEMVNP 852
Cdd:cd11972     5 VVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGL-FPGNYVESIMHY 60
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
667-741 1.44e-08

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 52.97  E-value: 1.44e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  667 EWYHASLTRAQAEHMLMRVPrDGAFLVRKRNEPNSY-AISFRAEGKIKHCRVQQEGQTVMLGNS-----EFDSLVDLISY 740
Cdd:cd09923     1 GWYWGGITRYEAEELLAGKP-EGTFLVRDSSDSRYLfSVSFRTYGRTLHARIEYSNGRFSFDSSdpsvpRFPCVVELIEH 79

                  .
gi 530418161  741 Y 741
Cdd:cd09923    80 Y 80
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
796-848 1.49e-08

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212739 [Multi-domain]  Cd Length: 53  Bit Score: 51.86  E-value: 1.49e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11805     2 VQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGI-FPANYVQP 53
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
548-641 1.55e-08

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 53.48  E-value: 1.55e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSF--W---RNGKVQHCRIHSRQDAGtpkFF 622
Cdd:cd10366     3 EEWYFGKMG-----RKDAERLL----LNPGNQRGIFLVRESETTKGAYSLSIrdWdevRGDNVKHYKIRKLDNGG---YY 70
                          90
                  ....*....|....*....
gi 530418161  623 LTDNLVFDSLYDLITHYQQ 641
Cdd:cd10366    71 ITTRAQFDTLQKLVKHYTE 89
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
550-645 1.73e-08

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 53.45  E-value: 1.73e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDNLVF 629
Cdd:cd09940     7 WFVGEME-----RDTAENRLE------NRPDGTYLVRVRPQGETQYALSIKYNGDVKHMKIEQRSDG---LYYLSESRHF 72
                          90
                  ....*....|....*.
gi 530418161  630 DSLYDLITHYQQVPLR 645
Cdd:cd09940    73 KSLVELVNYYERNSLG 88
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
550-648 1.75e-08

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 54.26  E-value: 1.75e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietgapDGSFLVRESETFVGDYTLS-FWRNgKVQH---CRIHSRQ-DAGTPKFFLT 624
Cdd:cd10337     8 WYHGRIP-----RQVAESLVQR--------EGDFLVRDSLSSPGDYVLTcRWKG-QPLHfkiNRVVLRPsEAYTRVQYQF 73
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 530418161  625 DNLVFDSLYDLITHYQ--------------------QVPLRCNE 648
Cdd:cd10337    74 EDEQFDSIPALVHFYVgnrrpisqasgaiisrpvnrTVPLRCLE 117
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
796-847 1.97e-08

C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212883  Cd Length: 53  Bit Score: 51.75  E-value: 1.97e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11950     2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGL-FPANYVA 52
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
796-848 2.20e-08

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 51.44  E-value: 2.20e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 530418161   796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:pfam07653    2 GRVIFDYVGTDKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVG-LVPSTAVEE 53
SH3_FCHSD1_2 cd11895
Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain ...
796-849 3.16e-08

Second Src Homology 3 domain of FCH and double SH3 domains protein 1; FCHSD1 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212828  Cd Length: 58  Bit Score: 51.12  E-value: 3.16e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQE----GGWWRGDYGGKKQLwFPSNYVEEM 849
Cdd:cd11895     2 ARALYSYTGQSPEELSFPEGALIRLLPRAQdgvdDGFWRGEFGGRVGV-FPSLLVEEL 58
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
796-847 3.28e-08

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212777 [Multi-domain]  Cd Length: 53  Bit Score: 50.88  E-value: 3.28e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQ-EGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11843     2 VRALYDYEGQESDELSFKAGDILTKLEEEdEQGWCKGRLDGRVGL-YPANYVE 53
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
550-643 3.59e-08

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 52.04  E-value: 3.59e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEYcietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDNLVF 629
Cdd:cd10348     2 WLHGALD-----RNEAVEILKQK----ADADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDK---WFYIDDGPYF 69
                          90
                  ....*....|....
gi 530418161  630 DSLYDLITHYQQVP 643
Cdd:cd10348    70 ESLEHLIEHYTQFA 83
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
797-847 3.86e-08

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 51.05  E-value: 3.86e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQ--EGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRRGV-FPDNFVK 54
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
548-658 4.17e-08

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 52.35  E-value: 4.17e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLTEycietgapDGSFLVRESETFVGDYTLSfwrngkvqhcRIHSrqdaGTPKFFL---- 623
Cdd:cd09925     7 EPWYHGKMS-----RRDAESLLQT--------DGDFLVRESTTTPGQYVLT----------GMQN----GQPKHLLlvdp 59
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 530418161  624 -----TDNLVFDSLYDLITHYQQ--VPLRCNEFEMRLSEPVP 658
Cdd:cd09925    60 egvvrTKDRVFESISHLINYHVTngLPIISEGSELHLRRPVR 101
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
550-646 4.40e-08

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 52.20  E-value: 4.40e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLgagrdgrhiaERLLTEYCIETGAPD--GSFLVRESETFVGDYTLSFWRNGKVQHCRIhSRQDAGTPKfflTDNL 627
Cdd:cd10412    10 WFHGPI----------SRVKAAQLVQLQGPDahGVFLVRQSETRRGEYVLTFNFQGRAKHLRL-SLTERGQCR---VQHL 75
                          90       100
                  ....*....|....*....|.
gi 530418161  628 VFDSLYDLITHYQQ--VPLRC 646
Cdd:cd10412    76 HFPSVVDMLHHFQRspIPLEC 96
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
797-846 4.65e-08

Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CD2AP. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212989  Cd Length: 57  Bit Score: 50.59  E-value: 4.65e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEG--GWWRGDYGGKKQLwFPSNYV 846
Cdd:cd12056     5 KALFHYEGTNEDELDFKEGEIILIISKDTGepGWWKGELNGKEGV-FPDNFV 55
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
550-659 4.97e-08

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 52.20  E-value: 4.97e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETfVGDYTLSFWRNGKVQHCRIhSRQDAGtpKFFLTDNLVF 629
Cdd:cd10401     5 WFHGKIS-----REESEQIL----LIGSKTNGKFLIRERDN-NGSYALCLLHDGKVLHYRI-DKDKTG--KLSIPDGKKF 71
                          90       100       110
                  ....*....|....*....|....*....|...
gi 530418161  630 DSLYDLITHYQQVP---LRCnefemrLSEPVPQ 659
Cdd:cd10401    72 DTLWQLVEHYSYKPdglLRV------LTEPCPR 98
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
793-847 5.10e-08

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 50.54  E-value: 5.10e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  793 KCAVkaLFDYKAQREDELTFIKSAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVE 847
Cdd:cd12142     1 YCRV--LFDYNPVAPDELALKKGDVIEVISKETEdeGWWEGELNGRRG-FFPDNFVM 54
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
796-845 5.30e-08

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212816  Cd Length: 55  Bit Score: 50.36  E-value: 5.30e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQL----WFPSNY 845
Cdd:cd11883     2 VVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSGKvkrgWFPSNY 55
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
796-851 5.36e-08

Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane. Abi1 interact with formins to promote protrusions at the leading edge of motile cells. It also is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement. Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212904 [Multi-domain]  Cd Length: 59  Bit Score: 50.79  E-value: 5.36e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEEMVN 851
Cdd:cd11971     2 VVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGL-FPGNYVESIMH 56
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
664-745 7.41e-08

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 51.43  E-value: 7.41e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLMRVPR-DGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQE--GQTVMLGNSEFDSLVDLISY 740
Cdd:cd10401     1 EKMPWFHGKISREESEQILLIGSKtNGKFLIRERDNNGSYALCLLHDGKVLHYRIDKDktGKLSIPDGKKFDTLWQLVEH 80

                  ....*
gi 530418161  741 YEKHP 745
Cdd:cd10401    81 YSYKP 85
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
548-641 7.53e-08

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 51.52  E-value: 7.53e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSFwRN------GKVQHCRIHSRQDAGtpkF 621
Cdd:cd10364     3 EEWFFKDIT-----RKDAERQL----LAPGNSAGAFLIRESETLKGSYSLSV-RDydpqhgDVIKHYKIRSLDNGG---Y 69
                          90       100
                  ....*....|....*....|
gi 530418161  622 FLTDNLVFDSLYDLITHYQQ 641
Cdd:cd10364    70 YISPRITFPCISDMIKHYQK 89
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
798-848 8.15e-08

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 49.94  E-value: 8.15e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGkKQLWFPSNYVEE 848
Cdd:cd11856     4 AIADYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGD-KEGWVPASYLEP 53
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
797-847 9.23e-08

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212770 [Multi-domain]  Cd Length: 55  Bit Score: 49.66  E-value: 9.23e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVE 847
Cdd:cd11836     3 RALYAFEARNPDEISFQPGDIIQVDESQVAepGWLAGELKGKTG-WFPANYVE 54
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
798-848 1.09e-07

Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the Saccharomyces cerevisiae proteins, Ysc84p (also called LAS17-binding protein 4, Lsb4p) and Lsb3p, and similar fungal proteins. They contain an N-terminal SYLF domain (also called DUF500) and a C-terminal SH3 domain. Ysc84p localizes to actin patches and plays an important in actin polymerization during endocytosis. The N-terminal domain of both Ysc84p and Lsb3p can bind and bundle actin filaments. A study of the yeast SH3 domain interactome predicts that the SH3 domains of Lsb3p and Lsb4p may function as molecular hubs for the assembly of endocytic complexes. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212776 [Multi-domain]  Cd Length: 55  Bit Score: 49.73  E-value: 1.09e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGG--WWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11842     4 ALYDFAGEQPGDLAFQKGDIITILKKSDSQndWWTGRIGGREGI-FPANYVEL 55
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
798-848 1.10e-07

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212809 [Multi-domain]  Cd Length: 58  Bit Score: 49.82  E-value: 1.10e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEG-----GWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11876     4 ALFDYDARGEDELTLRRGQPVEVLSKDAAvsgdeGWWTGKIGDKVGI-FPSNYVAP 58
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
668-741 1.10e-07

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 50.34  E-value: 1.10e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  668 WYHASLTRAQAEHMLMRVPRD-GAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLGNSEFDSLVDLISYY 741
Cdd:cd10360     2 WYFSGISRTQAQQLLLSPPNEpGAFLIRpSESSLGGYSLSVRAQAKVCHYRICMapSGSLYLQKGRLFPGLEELLAYY 79
PH_PLC_fungal cd13360
Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been ...
29-134 1.32e-07

Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been characterized in the yeast Saccharomyces cerevisiae via deletion studies which resulted in a pleiotropic phenotype, with defects in growth, carbon source utilization, and sensitivity to osmotic stress and high temperature. Unlike Saccharomyces several other fungi including Neurospora crassa, Cryphonectria parasitica , and Magnaporthe oryzae (Mo) have several PLC proteins, some of which lack a PH domain, with varied functions. MoPLC1-mediated regulation of Ca2+ level is important for conidiogenesis and appressorium formation while both MoPLC2 and MoPLC3 are required for asexual reproduction, cell wall integrity, appressorium development, and pathogenicity. The fungal PLCs in this hierarchy contain an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241514  Cd Length: 118  Bit Score: 51.41  E-value: 1.32e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   29 LEVGTVMTLFySKKSQRpeRKTFQVKLETRQITWSRGadKIEGAIDIREIKEIRPGKTSRDfdrYQEDpaFRPDQSH--- 105
Cdd:cd13360     1 LRQGTPLLKV-TKKKKK--RILFKLDPESGKITWDSK--KPSKSLYIDDIKEIRTGEDARN---YREE--FGISEEFedr 70
                          90       100       110
                  ....*....|....*....|....*....|.
gi 530418161  106 CFVILYGMEF--RLKTLSLQATSEDEVNMWI 134
Cdd:cd13360    71 WITIIYFVPKknKLKTLHLIADTEEDFKLWT 101
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
548-639 1.34e-07

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 51.02  E-value: 1.34e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLS---FWRN-GK-VQHCRIHSRQDAGtpkFF 622
Cdd:cd10362     3 EPWFFKNLS-----RNDAERQL----LAPGNTHGSFLIRESETTAGSFSLSvrdFDQNqGEvVKHYKIRNLDNGG---FY 70
                          90
                  ....*....|....*..
gi 530418161  623 LTDNLVFDSLYDLITHY 639
Cdd:cd10362    71 ISPRITFPGLHELVRHY 87
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
668-756 1.47e-07

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 50.90  E-value: 1.47e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPRDGAFLVRK--------------RNEPNSYAISFRAEGKIkhcrVQQEGQTVMLgnSEFDS 733
Cdd:cd10343     5 WYHGNITRSKAEELLSKAGKDGSFLVRDsesvsgayalcvlyQNCVHTYRILPNAEDKL----SVQASEGVPV--RFFTT 78
                          90       100
                  ....*....|....*....|...
gi 530418161  734 LVDLISYYEKHPLYRKMKLRYPI 756
Cdd:cd10343    79 LPELIEFYQKENMGLVTHLLYPV 101
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
549-637 1.67e-07

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 51.07  E-value: 1.67e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  549 KWFHGKLgagrDGRHIAERLlteycieTGAPDGSFLVRESETFVGDYTLS-FWRNGKVQHCRIHSRQDAgtpkfFLTDNL 627
Cdd:cd10356    11 AWFHGDI----STSESENRL-------NGKPEGTFLVRFSTSEPGAYTISkVSKNGGISHQRIHRPGGK-----FQVNNS 74
                          90
                  ....*....|
gi 530418161  628 VFDSLYDLIT 637
Cdd:cd10356    75 KYLSVKELIA 84
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
548-641 1.81e-07

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 50.73  E-value: 1.81e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSF-----WRNGKVQHCRIHSRQDAGtpkFF 622
Cdd:cd10363     3 EEWFFKGIS-----RKDAERQL----LAPGNMLGSFMIRDSETTKGSYSLSVrdydpQHGDTVKHYKIRTLDNGG---FY 70
                          90
                  ....*....|....*....
gi 530418161  623 LTDNLVFDSLYDLITHYQQ 641
Cdd:cd10363    71 ISPRSTFSTLQELVDHYKK 89
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
1090-1223 1.84e-07

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 50.53  E-value: 1.84e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1090 ISIEVLGARHLPKNGRGIVC-PFVEIEVAGaeydSTKQKTEfvgqsvfpvillillghckplptshpilshgdlkpfvva 1168
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSdPYVKVSLGG----KQKFKTK--------------------------------------- 37
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 530418161 1169 fTVDNGLNPVWPAKpFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLK 1223
Cdd:cd00030    38 -VVKNTLNPVWNET-FEFPVLDPESDTLTVEVWDKDRFSKDDFLGEVEIPLSELL 90
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
801-847 1.97e-07

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773  Cd Length: 58  Bit Score: 48.87  E-value: 1.97e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  801 DYKAQREDELTFIKSAIIQNVEKQEGGWWRGDY---GGKKQL-WFPSNYVE 847
Cdd:cd11839     7 PFTATAENQLSLAVGQLVLVRKKSPSGWWEGELqarGKKRQIgWFPANYVK 57
SH2_SOCS6 cd10387
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
668-738 2.05e-07

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198250  Cd Length: 100  Bit Score: 50.22  E-value: 2.05e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  668 WYHASLTRAQAEHMLMRVPrDGAFLVRKRNEpNSY--AISFRAEGKIKHCRVQQEGQTVMLGN----SEFDSLVDLI 738
Cdd:cd10387    12 WYWGPITRWEAEGKLANVP-DGSFLVRDSSD-DRYllSLSFRSHGKTLHTRIEHSNGRFSFYEqpdvEGHTSIVDLI 86
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
800-849 2.21e-07

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212986  Cd Length: 56  Bit Score: 48.68  E-value: 2.21e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  800 FDYKAQREDELTFIKSAIIQNVEK-QEGGWWRGDYGGKKQLwFPSNYVEEM 849
Cdd:cd12053     6 YDYDAVHEDELTIRVGEIIRNVKKlEEEGWLEGELNGRRGM-FPDNFVKEI 55
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
796-847 2.36e-07

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212723 [Multi-domain]  Cd Length: 55  Bit Score: 48.47  E-value: 2.36e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG------DYGgkkqlWFPSNYVE 847
Cdd:cd11789     2 YRAMYDYAAADDDEVSFQEGDVIINVEIIDDGWMEGtvqrtgQSG-----MLPANYVE 54
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
668-758 2.43e-07

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 50.40  E-value: 2.43e-07
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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRvPRDGAFLVRKR-NEPNSYAISFRAEGKIKHCRV-QQEGQTVMLGNSEFDSLVDLISYYEKHP 745
Cdd:cd10405     7 WYAGPMERAGAESILAN-RSDGTYLVRQRvKDAAEFAISIKYNVEVKHIKImTAEGLYRITEKKAFRGLTELVEFYQQNS 85
                          90
                  ....*....|....*...
gi 530418161  746 LYRKMK-----LRYPINE 758
Cdd:cd10405    86 LKDCFKsldttLQFPFKE 103
SH2_C-SH2_Zap70_Syk_like cd10345
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
668-740 2.45e-07

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198208  Cd Length: 95  Bit Score: 50.07  E-value: 2.45e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  668 WYHASLTRAQAEHMLMR-VPRDGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQE--GQTVMLGNSEFDSLVDLISY 740
Cdd:cd10345     2 WFHGKISREESEQIVLIgSKTNGKFLIRARDNNGSYALCLLHEGKVLHYRIDKDktGKLSIPEGKKFDTLWQLVEH 77
SH3_PACSIN1-2 cd11998
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) ...
796-847 2.57e-07

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 1 (PACSIN1) and PACSIN 2; PACSIN 1 or Syndapin I (Synaptic dynamin-associated protein I) is expressed specifically in the brain and is localized in neurites and synaptic boutons. It binds the brain-specific proteins dynamin I, synaptojanin, synapsin I, and neural Wiskott-Aldrich syndrome protein (nWASP), and functions as a link between the cytoskeletal machinery and synaptic vesicle endocytosis. PACSIN 1 interacts with huntingtin and may be implicated in the neuropathology of Huntington's disease. PACSIN 2 or Syndapin II is expressed ubiquitously and is involved in the regulation of tubulin polymerization. It associates with Golgi membranes and forms a complex with dynamin II which is crucial in promoting vesicle formation from the trans-Golgi network. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212931 [Multi-domain]  Cd Length: 56  Bit Score: 48.79  E-value: 2.57e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQ-EGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:cd11998     3 VRALYDYDGQEQDELSFKAGDELTKLEDEdEQGWCKGRLDSGQVGLYPANYVE 55
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
663-742 2.88e-07

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 50.31  E-value: 2.88e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLMRV-PRDGAFLVR-KRNEPNSYAISFRAEGKIKHCR---VQQEGQ---TVMLGNSEFDSL 734
Cdd:cd10414     2 HRSQPWFHHKISRDEAQRLIIQQgLVDGVFLVRdSQSNPRTFVLSMSHGQKIKHFQiipVEDDGElfhTLDDGHTRFTDL 81

                  ....*...
gi 530418161  735 VDLISYYE 742
Cdd:cd10414    82 IQLVEFYQ 89
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
549-648 2.96e-07

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 49.64  E-value: 2.96e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  549 KWFHGKLGagrdgRHIAERLLTEYCIEtgapdGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDagtpkFFLTDNLV 628
Cdd:cd10408     2 PWYYGKVT-----RHQAEMALNERGNE-----GDFLIRDSESSPNDFSVSLKAQGKNKHFKVQLKEC-----VYCIGQRK 66
                          90       100
                  ....*....|....*....|
gi 530418161  629 FDSLYDLITHYQQVPLRCNE 648
Cdd:cd10408    67 FSSMEELVEHYKKAPIFTSE 86
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
796-848 3.25e-07

Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. It has only been characterized in silico and its function is unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212827  Cd Length: 56  Bit Score: 48.40  E-value: 3.25e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQ---EGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11894     2 VKALYDYEGQTDDELSFPEGAIIRILNKEnqdDDGFWEGEFNGRIGV-FPSVLVEE 56
PLN02223 PLN02223
phosphoinositide phospholipase C
998-1231 3.36e-07

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 54.64  E-value: 3.36e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  998 KKFLqynrlqlsRIYPKGQRLDS-SNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTMRDEA--- 1073
Cdd:PLN02223  326 KKFL--------RTRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNAGpsg 397
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1074 -FDPFDKSslrglepcaISIEVLGARHLpkNGRGIVCPF-------------VEIEVAGAEYDSTKQKTefvgqsvfpvi 1139
Cdd:PLN02223  398 vFYPTENP---------VVVKILKVKIY--MGDGWIVDFkkrigrlskpdlyVRISIAGVPHDEKIMKT----------- 455
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161 1140 llillghckplptshpilshgdlkpfvvafTV-DNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFP 1218
Cdd:PLN02223  456 ------------------------------TVkNNEWKPTW-GEEFTFPLTYPDLALISFEVYDYEVSTADAFCGQTCLP 504
                         250
                  ....*....|...
gi 530418161 1219 VKGLKTGYRAVPL 1231
Cdd:PLN02223  505 VSELIEGIRAVPL 517
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
797-848 3.51e-07

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 48.01  E-value: 3.51e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQ-EGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11830     3 KARYDFCARDMRELSLKEGDVVKIYNKKgQQGWWRGEINGRIG-WFPSTYVEE 54
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
798-848 3.54e-07

Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. The SH3C of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212772 [Multi-domain]  Cd Length: 52  Bit Score: 48.18  E-value: 3.54e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11838     4 ALYPYESNEPGDLTFNAGDVIL-VTKKDGEWWTGTIGDRTGI-FPSNYVRP 52
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
664-755 4.49e-07

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 49.04  E-value: 4.49e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLMRVPRD-GAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLGNSEFDSLVDLIS 739
Cdd:cd10370     1 EAEPWYFGKIKRIEAEKKLLLPENEhGAFLIRdSESRHNDYSLSVRDGDTVKHYRIRQldEGGFFIARRTTFRTLQELVE 80
                          90
                  ....*....|....*.
gi 530418161  740 YYEKHPLYRKMKLRYP 755
Cdd:cd10370    81 HYSKDSDGLCVNLRKP 96
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
667-746 4.90e-07

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198199  Cd Length: 102  Bit Score: 49.12  E-value: 4.90e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  667 EWYHASLTRAQAEHMLMRVPRdGAFLVRKRNEPNSYAISFRAEGKIKH--CRVQQEGQTVMLGN-SEFDSLVDLISYYEK 743
Cdd:cd09946     8 EWFHGAISREAAENMLESQPL-GSFLIRVSHSHVGYTLSYKAQSSCRHfmVKLLDDGTFMIPGEkVAHTSLHALVTFHQQ 86

                  ...
gi 530418161  744 HPL 746
Cdd:cd09946    87 KPI 89
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
668-741 5.07e-07

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 50.03  E-value: 5.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMlmrVPRDGAFLVRK-RNEPNSYAISFRAEGKIKH-------CRVQQEGQTVM--LGNSEFDSLVDL 737
Cdd:cd10337     8 WYHGRIPRQVAESL---VQREGDFLVRDsLSSPGDYVLTCRWKGQPLHfkinrvvLRPSEAYTRVQyqFEDEQFDSIPAL 84

                  ....
gi 530418161  738 ISYY 741
Cdd:cd10337    85 VHFY 88
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
665-739 5.29e-07

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 49.53  E-value: 5.29e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  665 SKEWYHASLTRAQAEHMLMRVPrDGAFLVR-KRNEPNSYAIS-FRAEGKIKHCRVQQEGQTVMLGNSEFDSLVDLIS 739
Cdd:cd10356     9 ECAWFHGDISTSESENRLNGKP-EGTFLVRfSTSEPGAYTISkVSKNGGISHQRIHRPGGKFQVNNSKYLSVKELIA 84
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
797-848 5.93e-07

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 47.63  E-value: 5.93e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQ-EGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11976     3 KARYDFCARDRSELSLKEGDIIKILNKKgQQGWWRGEIYGRVG-WFPANYVEE 54
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
797-848 6.45e-07

Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CIN85. SH3B has been shown to bind Cbl proline-rich peptides and ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212988  Cd Length: 53  Bit Score: 47.30  E-value: 6.45e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd12055     3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGM-FPSNFIKE 53
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
663-742 6.93e-07

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197  Cd Length: 108  Bit Score: 48.96  E-value: 6.93e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLMRV-PRDGAFLVR--KRNePNSYAISFRAEGKIKHCRVQ---QEGQ---TVMLGNSEFDS 733
Cdd:cd09944     2 HRSQPWFHGGISRDEAARLIRQQgLVDGVFLVResQSN-PGAFVLSLKHGQKIKHYQIIpieDEGQwyfTLDDGVTKFYD 80

                  ....*....
gi 530418161  734 LVDLISYYE 742
Cdd:cd09944    81 LLQLVEFYQ 89
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
669-738 7.09e-07

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 48.51  E-value: 7.09e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418161  669 YHASLTRAQAEhMLMRVPRDGAFLVRKRN-EPNSYAISFRAEGKIKHCRVQQEGQTVML--GNSEFDSLVDLI 738
Cdd:cd10352     9 YHGLISREEAE-QLLSGASDGSYLIRESSrDDGYYTLSLRFNGKVKNYKLYYDGKNHYHyvGEKRFDTIHDLV 80
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
546-644 7.83e-07

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198274  Cd Length: 97  Bit Score: 48.46  E-value: 7.83e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  546 SNEKWFHGKLgagrdgrhiaERLLTEYCIETGAP--DGSFLVRESETFVGDYTLSFWRNGKVQHCRIhSRQDAGTPKffl 623
Cdd:cd10411     6 SDYPWFHGTL----------SRVKAAQLVLAGGPrsHGLFVIRQSETRPGEYVLTFNFQGKAKHLRL-SLNGHGQCH--- 71
                          90       100
                  ....*....|....*....|.
gi 530418161  624 TDNLVFDSLYDLITHYQQVPL 644
Cdd:cd10411    72 VQHLWFQSVFDMLRHFHTHPI 92
SH2_SH2D2A cd10416
Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains ...
668-746 8.00e-07

Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198279  Cd Length: 102  Bit Score: 48.88  E-value: 8.00e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPRdGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQ--EGQTVMLG-NSEFDSLVDLISYYEKH 744
Cdd:cd10416     9 WFHGFITRREAERLLEPKPQ-GCYLVRFSESAVTFVLTYRSRTCCRHFLLAQlrDGRHVVLGeDSAHARLQDLLLHYTAH 87

                  ..
gi 530418161  745 PL 746
Cdd:cd10416    88 PL 89
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
548-641 8.41e-07

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 48.80  E-value: 8.41e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFhgklgAGRDGRHIAERLLTEycietGAPDGSFLVRESeTFVGDYTLSFW------RNGKVQHCRIHSRQDAgtpKF 621
Cdd:cd10399     6 YDWF-----AGNISRSQSEQLLRQ-----KGKEGAFMVRNS-SQVGMYTVSLFskavndKKGTVKHYHVHTNAEN---KL 71
                          90       100
                  ....*....|....*....|
gi 530418161  622 FLTDNLVFDSLYDLITHYQQ 641
Cdd:cd10399    72 YLAENYCFDSIPKLIHYHQH 91
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
798-847 8.52e-07

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212758 [Multi-domain]  Cd Length: 53  Bit Score: 46.98  E-value: 8.52e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11824     4 VLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGL-VPGTYLE 52
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
550-643 9.08e-07

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 48.55  E-value: 9.08e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLgAGRDgrhiAERLLTEYCIetgapDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpkFFLTDNLVF 629
Cdd:cd10340     2 WFHPVI-SGIE----AENLLKTRGV-----DGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDY----YDLYGGEKF 67
                          90
                  ....*....|....
gi 530418161  630 DSLYDLITHYQQVP 643
Cdd:cd10340    68 ATLSELVQYYMEQH 81
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
797-845 1.03e-06

Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212752 [Multi-domain]  Cd Length: 50  Bit Score: 46.71  E-value: 1.03e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNY 845
Cdd:cd11818     3 RALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRGKSGI-FPKNF 50
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
550-639 1.09e-06

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 47.58  E-value: 1.09e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHS-----RQDAGTPKFFLt 624
Cdd:cd09923     2 WYWGGIT-----RYEAEELLA------GKPEGTFLVRDSSDSRYLFSVSFRTYGRTLHARIEYsngrfSFDSSDPSVPR- 69
                          90
                  ....*....|....*
gi 530418161  625 dnlvFDSLYDLITHY 639
Cdd:cd09923    70 ----FPCVVELIEHY 80
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
796-846 1.14e-06

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212754 [Multi-domain]  Cd Length: 54  Bit Score: 46.69  E-value: 1.14e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11820     3 VRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGL-FPANFV 52
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
550-657 1.15e-06

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 48.19  E-value: 1.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIhSRQDAGtpKFFLTDN-LV 628
Cdd:cd09945     3 WYHGAIT-----RIEAESLLR------PCKEGSYLVRNSESTKQDYSLSLKSAKGFMHMRI-QRNETG--QYILGQFsRP 68
                          90       100       110
                  ....*....|....*....|....*....|.
gi 530418161  629 FDSLYDLITHY--QQVPLRCNEfEMRLSEPV 657
Cdd:cd09945    69 FETIPEMIRHYclNKLPVRGAE-HMCLLEPV 98
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
550-641 1.35e-06

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 48.16  E-value: 1.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAErlltEYCIETGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHsRQDAGTpkFFLTDNLVF 629
Cdd:cd09938     3 FFYGSIT-----REEAE----EYLKLAGMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIE-RQLNGT--YAIAGGKAH 70
                          90
                  ....*....|..
gi 530418161  630 DSLYDLITHYQQ 641
Cdd:cd09938    71 CGPAELCEYHST 82
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
799-847 1.36e-06

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212895 [Multi-domain]  Cd Length: 54  Bit Score: 46.33  E-value: 1.36e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  799 LFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:cd11962     5 LYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMGTNSKGESGLFPSNYVE 53
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
543-644 1.44e-06

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 47.47  E-value: 1.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  543 ELHSNEKWFHGKLGagrdgRHIAERLLTeycieTGAPDGSFLVRESETFVGDYTLSFWRNGKVQHcrIHSRQDAGTPKFF 622
Cdd:cd10355     1 ELLQSLGWYHGNLT-----RHAAEALLL-----SNGVDGSYLLRNSNEGTGLFSLSVRAKDSVKH--FHVEYTGYSFKFG 68
                          90       100
                  ....*....|....*....|..
gi 530418161  623 LTdnlVFDSLYDLITHYQQVPL 644
Cdd:cd10355    69 FN---EFSSLQDFVKHFANQPL 87
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
549-645 1.49e-06

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198199  Cd Length: 102  Bit Score: 47.96  E-value: 1.49e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  549 KWFHGKLGagrdgRHIAERLLTeycietGAPDGSFLVRESETFVGdYTLSFWRNGKVQHCRIHSRQDAGTpkFFLTDNLV 628
Cdd:cd09946     8 EWFHGAIS-----REAAENMLE------SQPLGSFLIRVSHSHVG-YTLSYKAQSSCRHFMVKLLDDGTF--MIPGEKVA 73
                          90
                  ....*....|....*..
gi 530418161  629 FDSLYDLITHYQQVPLR 645
Cdd:cd09946    74 HTSLHALVTFHQQKPIE 90
SH3_Bbc1 cd11887
Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces ...
796-848 1.54e-06

Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces cerevisiae Bbc1p, also called Mti1p (Myosin tail region-interacting protein), and similar proteins. Bbc1p interacts with and regulates type I myosins in yeast, Myo3p and Myo5p, which are involved in actin cytoskeletal reorganization. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex. Bbc1p contains an N-terminal SH3 domain. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212820 [Multi-domain]  Cd Length: 60  Bit Score: 46.57  E-value: 1.54e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDY----GGKKQLWFPSNYVEE 848
Cdd:cd11887     4 VKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEYvdsnGNTKEGIFPKNFVEV 60
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
668-746 1.57e-06

Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198209  Cd Length: 97  Bit Score: 47.80  E-value: 1.57e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPRD--GAFLVRK-RNEPNSYAISFRAEGKIKH----------CRVQQegqtvmlgnSEFDSL 734
Cdd:cd10346    10 WFHGTLSRSDAAQLVLHSGADghGVFLVRQsETRRGEFVLTFNFQGRAKHlrltlnekgqCRVQH---------LWFPSI 80
                          90
                  ....*....|..
gi 530418161  735 VDLISYYEKHPL 746
Cdd:cd10346    81 FDMLEHFRQNPI 92
SH3_Nebulette_C cd11935
C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a ...
797-847 1.60e-06

C-terminal Src Homology 3 domain of Nebulette and LIM-nebulette (or Lasp2); Nebulette is a cardiac-specific protein that localizes to the Z-disc. It interacts with tropomyosin and is important in stabilizing actin thin filaments in cardiac muscles. Polymorphisms in the nebulette gene are associated with dilated cardiomyopathy, with some mutations resulting in severe heart failure. Nebulette is a 107kD protein that contains an N-terminal acidic region, multiple nebulin repeats, and a C-terminal SH3 domain. LIM-nebulette, also called Lasp2 (LIM and SH3 domain protein 2), is an alternatively spliced variant of nebulette. Although it shares a gene with nebulette, Lasp2 is not transcribed from a muscle-specific promoter, giving rise to its multiple tissue expression pattern with highest amounts in the brain. It can crosslink actin filaments and it affects cell spreading. Lasp2 is a 34kD protein containing an N-terminal LIM domain, three nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212868 [Multi-domain]  Cd Length: 58  Bit Score: 46.54  E-value: 1.60e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG--DYGGKKQLwFPSNYVE 847
Cdd:cd11935     4 RAMYDYSAQDEDEVSFRDGDYIVNVQPIDEGWMYGtvQRTGRTGM-LPANYIE 55
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
796-846 1.67e-06

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212897 [Multi-domain]  Cd Length: 55  Bit Score: 46.48  E-value: 1.67e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11964     3 VRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGL-FPSNFV 52
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
663-761 1.68e-06

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198278  Cd Length: 108  Bit Score: 48.09  E-value: 1.68e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  663 HESKEWYHASLTRAQAEHMLMRVPR-DGAFLVR-KRNEPNSYAISFRAEGKIKHCRV---QQEGQTVML---GNSEFDSL 734
Cdd:cd10415     2 HRTQHWFHGRISREESHRIIKQQGLvDGLFLLRdSQSNPKAFVLTLCHHQKIKNFQIlpcEDDGQTFFSlddGNTKFSDL 81
                          90       100
                  ....*....|....*....|....*..
gi 530418161  735 VDLISYYEKHPLYRKMKLRYPINEEAL 761
Cdd:cd10415    82 IQLVDFYQLNKGVLPCKLKHHCIRVAL 108
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
547-641 1.71e-06

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 47.14  E-value: 1.71e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  547 NEKWFHGKLGagrdgRHIAERLLTEycietgapDGSFLVRESETFVGD---YTLSFWRNGKVQHCRIHSRQDAgtpKFFL 623
Cdd:cd10361     5 NEPYYHGLLP-----REDAEELLKN--------DGDFLVRKTEPKGGGkrkLVLSVRWDGKIRHFVINRDDGG---KYYI 68
                          90
                  ....*....|....*...
gi 530418161  624 tDNLVFDSLYDLITHYQQ 641
Cdd:cd10361    69 -EGKSFKSISELINYYQK 85
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
550-641 2.03e-06

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 47.39  E-value: 2.03e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietGAPDGSFLVRESETfVGDYTLSFW----RNGKVQHCRIHSRQDAgtpKFFLTD 625
Cdd:cd09934     8 WYVGDMS-----RQRAESLLKQ-----EDKEGCFVVRNSST-KGLYTVSLFtkvpGSPHVKHYHIKQNARS---EFYLAE 73
                          90
                  ....*....|....*.
gi 530418161  626 NLVFDSLYDLItHYQQ 641
Cdd:cd09934    74 KHCFETIPELI-NYHQ 88
SH2_SH2B1 cd10410
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, ...
546-644 2.18e-06

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, PSM), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198273  Cd Length: 97  Bit Score: 47.32  E-value: 2.18e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  546 SNEKWFHGKLGagrdgRHIAERLLTEYCIetgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPkfflTD 625
Cdd:cd10410     6 SGYPWFHGMLS-----RLKAAQLVLEGGT---GSHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSLNEEGQCR----VQ 73
                          90
                  ....*....|....*....
gi 530418161  626 NLVFDSLYDLITHYQQVPL 644
Cdd:cd10410    74 HLWFQSIFDMLEHFRVHPI 92
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
797-847 2.29e-06

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 45.80  E-value: 2.29e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEgGWWRGDYGGKKQlWFPSNYVE 847
Cdd:cd11990     3 QALCSWTAKKDNHLNFSKNDIITVLEQQE-NWWFGEVHGGRG-WFPKSYVK 51
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
668-757 2.41e-06

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 47.39  E-value: 2.41e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRV-PRDGAFLVRK-RNEPNSYAISFRAEGKIKHCRVQQE--GQTVMLGNSEFDSLVDLISYYEK 743
Cdd:cd09938     3 FFYGSITREEAEEYLKLAgMSDGLFLLRQsLRSLGGYVLSVCHGRKFHHYTIERQlnGTYAIAGGKAHCGPAELCEYHST 82
                          90
                  ....*....|....
gi 530418161  744 HPLYRKMKLRYPIN 757
Cdd:cd09938    83 DLDGLVCLLRKPCN 96
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
550-648 2.43e-06

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 47.34  E-value: 2.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEYCIEtgapdGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpkfFLTDNLVF 629
Cdd:cd10409     3 WYYGNVT-----RHQAECALNERGVE-----GDFLIRDSESSPSDFSVSLKAVGKNKHFKVQLVDNV-----YCIGQRRF 67
                          90
                  ....*....|....*....
gi 530418161  630 DSLYDLITHYQQVPLRCNE 648
Cdd:cd10409    68 NSMDELVEHYKKAPIFTSE 86
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
796-848 3.15e-06

Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the peroxisomal membrane, contains two transmembrane regions and a C-terminal SH3 domain. It binds to the peroxisomal targeting type I (PTS1) receptor Pex5p and the docking factor Pex14p through its SH3 domain. It is essential for both PTS1 and PTS2 protein import pathways into the peroxisomal matrix. Pex13p binds Pex14p, which contains a PxxP motif, in a classical fashion to the proline-rich ligand binding site of its SH3 domain. It binds the WxxxF/Y motif of Pex5p in a novel site that does not compete with Pex14p binding. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212705 [Multi-domain]  Cd Length: 60  Bit Score: 45.73  E-value: 3.15e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 530418161  796 VKALFDYK-AQREDELTFIKSAII-----QNVEKQEGGWWRGDYGGKKQLWFPSNYVEE 848
Cdd:cd11771     2 CRALYDFTpENPEMELSLKKGDIVavlskTDPLGRDSEWWKGRTRDGRIGWFPSNYVEV 60
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
798-846 3.30e-06

Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (or SH3C) of ITSN1 has been shown to bind many proteins including dynamin1/2, CIN85, c-Cbl, SHIP2, Reps1, synaptojanin-1, and WNK, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212924  Cd Length: 52  Bit Score: 45.36  E-value: 3.30e-06
                          10        20        30        40
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11991     4 AMYTYESNEQGDLTFQQGDVIL-VTKKDGDWWTGTVGDKTGV-FPSNYV 50
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
796-846 3.45e-06

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212896 [Multi-domain]  Cd Length: 57  Bit Score: 45.39  E-value: 3.45e-06
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11963     4 VRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGL-FPSNFV 53
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
668-746 3.55e-06

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198274  Cd Length: 97  Bit Score: 46.53  E-value: 3.55e-06
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gi 530418161  668 WYHASLTRAQAEHMLMRV-PRD-GAFLVRK-RNEPNSYAISFRAEGKIKHCR--VQQEGQtVMLGNSEFDSLVDLISYYE 742
Cdd:cd10411    10 WFHGTLSRVKAAQLVLAGgPRShGLFVIRQsETRPGEYVLTFNFQGKAKHLRlsLNGHGQ-CHVQHLWFQSVFDMLRHFH 88

                  ....
gi 530418161  743 KHPL 746
Cdd:cd10411    89 THPI 92
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
798-846 3.79e-06

Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus, impacts inflammation and immunity. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212992  Cd Length: 58  Bit Score: 45.53  E-value: 3.79e-06
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQ-----EGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd12059     4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGI-FPSNYV 56
SH3_SH3RF_3 cd11783
Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and ...
798-846 4.12e-06

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212717  Cd Length: 55  Bit Score: 45.08  E-value: 4.12e-06
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLW-FPSNYV 846
Cdd:cd11783     4 ALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTSLRTGQSGvFPGNYV 53
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
668-756 4.35e-06

Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198254  Cd Length: 98  Bit Score: 46.49  E-value: 4.35e-06
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gi 530418161  668 WYHASLTRAQAEHMLMRVpRDGAFLVRKRNEPNS-YAISFRAEGKIKHCRVQQ---EGQTVMLGNSEFDSLVDLISYY-- 741
Cdd:cd10391     3 WYHGSISRAEAESRLQPC-KEASYLVRNSESGNSkYSIALKTSQGCVHIIVAQtkdNKYTLNQTSAVFDSIPEVVHYYsn 81
                          90
                  ....*....|....*..
gi 530418161  742 EKHPL--YRKMKLRYPI 756
Cdd:cd10391    82 EKLPFkgAEHMTLLHPV 98
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
798-848 4.46e-06

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212911 [Multi-domain]  Cd Length: 56  Bit Score: 45.01  E-value: 4.46e-06
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQ-EGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11978     5 ARYDFCARDMRELSLLKGDVVKIYTKMsTNGWWRGEVNGRVG-WFPSTYVEE 55
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
550-657 4.48e-06

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198255  Cd Length: 98  Bit Score: 46.60  E-value: 4.48e-06
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gi 530418161  550 WFHGKLGagrdgRHIAERLLtEYCIEtgapdGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpKFFLTDN-LV 628
Cdd:cd10392     3 WYHGAIS-----RTDAENLL-RLCKE-----ASYLVRNSETSKNDFSLSLKSSQGFMHMKLSRTKEH---KYVLGQNsPP 68
                          90       100       110
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gi 530418161  629 FDSLYDLITHY--QQVPLRCNEfEMRLSEPV 657
Cdd:cd10392    69 FSSVPEIIHHYasRKLPIKGAE-HMSLLYPV 98
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
664-744 5.28e-06

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 46.20  E-value: 5.28e-06
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gi 530418161  664 ESKEWYHASLTRAQAEHMLMRVP-RDGAFLVRK-RNEPNSYAISF----RAEG-KIKHCRVQQ--EGQTVMLGNSEFDSL 734
Cdd:cd10365     1 QAEEWYFGKITRRESERLLLNAEnPRGTFLVREsETTKGAYCLSVsdfdNAKGlNVKHYKIRKldSGGFYITSRTQFNSL 80
                          90
                  ....*....|
gi 530418161  735 VDLISYYEKH 744
Cdd:cd10365    81 QQLVAYYSKH 90
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
796-846 5.92e-06

C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domains (SH3c) of the related proteins, GRB2 and GRAP2, have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212884  Cd Length: 53  Bit Score: 44.79  E-value: 5.92e-06
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11951     2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGF-FPRNYV 51
SH3_srGAP4 cd11956
Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, ...
798-846 6.12e-06

Src homology 3 domain of Slit-Robo GTPase Activating Protein 4; srGAP4, also called ARHGAP4, is highly expressed in hematopoietic cells and may play a role in lymphocyte differentiation. It is able to stimulate the GTPase activity of Rac1, Cdc42, and RhoA. In the nervous system, srGAP4 has been detected in differentiating neurites and may be involved in axon and dendritic growth. srGAPs are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212889  Cd Length: 55  Bit Score: 44.83  E-value: 6.12e-06
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11956     6 ACFDYTGRTAQELSFKRGDVLLLHSKASSDWWRGEHNGMRGL-IPHKYI 53
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
667-727 6.39e-06

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198251  Cd Length: 101  Bit Score: 46.19  E-value: 6.39e-06
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gi 530418161  667 EWYHASLTRAQAEHMLMRVPrDGAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQEGQTVMLG 727
Cdd:cd10388    11 GWYWGPMSWEDAEKVLSNKP-DGSFLVRdSSDDRYIFSLSFRSQGSVHHTRIEQYQGTFSLG 71
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
544-640 6.59e-06

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 46.08  E-value: 6.59e-06
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gi 530418161  544 LHSNEKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFL 623
Cdd:cd10414     1 IHRSQPWFHHKIS-----RDEAQRLI----IQQGLVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQIIPVEDDGELFHTL 71
                          90
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gi 530418161  624 TD-NLVFDSLYDLITHYQ 640
Cdd:cd10414    72 DDgHTRFTDLIQLVEFYQ 89
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
667-756 7.13e-06

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 46.16  E-value: 7.13e-06
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gi 530418161  667 EWYHASLTRAQAEHMLMRVPrDGAFLVRK-RNEPNSYAISFRAEG-----KIKHcRVQQEGQTVMLgnsEFDSLVDLISY 740
Cdd:cd09942     8 EWYWGDISREEVNEKMRDTP-DGTFLVRDaSTMKGDYTLTLRKGGnnkliKIFH-RDGKYGFSDPL---TFNSVVELINY 82
                          90       100
                  ....*....|....*....|.
gi 530418161  741 YEKHPL--YRK---MKLRYPI 756
Cdd:cd09942    83 YRNNSLaeYNRkldVKLLYPV 103
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
797-849 7.30e-06

First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212853 [Multi-domain]  Cd Length: 55  Bit Score: 44.62  E-value: 7.30e-06
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gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEEM 849
Cdd:cd11920     4 RAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGI-FPISYVEKL 55
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
795-845 7.99e-06

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212712 [Multi-domain]  Cd Length: 51  Bit Score: 44.41  E-value: 7.99e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  795 AVKALFDYKAQREDELTFIKSAIIQNVEKQEG-GWWRGDYGGKKQLwFPSNY 845
Cdd:cd11778     1 YVEALYDYEAQGDDEISIRVGDRIAVIRGDDGsGWTYGEINGVKGL-FPTSY 51
SH3_Tks4_2 cd12076
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
798-848 8.05e-06

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213009 [Multi-domain]  Cd Length: 54  Bit Score: 44.25  E-value: 8.05e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd12076     5 VIYPYTARDQDEINLEKGAVVEVIQKNLEGWWKIRYQGKEG-WAPASYLKK 54
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
797-848 8.55e-06

First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN2 is expected to bind many protein partners, similar to ITSN1 which has been shown to bind Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212921 [Multi-domain]  Cd Length: 57  Bit Score: 44.48  E-value: 8.55e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQ--EGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11988     5 RALYPFEARNHDEMSFNAGDIIQVDEKTvgEPGWLYGSFQGNFG-WFPCNYVEK 57
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
664-756 9.15e-06

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198259  Cd Length: 108  Bit Score: 45.94  E-value: 9.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAIS----FRAEGK--IKHCRVQQ----EGQTVMLGNSEFDS 733
Cdd:cd10396     4 DQYEWYNKNINRSKAEKLLRDEGKEGGFMVRDSSQPGLYTVSlytkAGGEGNpcIRHYHIKEtndsPKKYYLAEKHVFNS 83
                          90       100
                  ....*....|....*....|...
gi 530418161  734 LVDLISYYEKHPLYRKMKLRYPI 756
Cdd:cd10396    84 IPELIEYHKHNAAGLVTRLRYPV 106
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
668-741 9.54e-06

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 44.82  E-value: 9.54e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  668 WYHASLTRAQAEHMLMRVPRdGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQE--GQTVMLGN-SEFDSLVDLISYY 741
Cdd:cd10349     2 WFHGFITRREAERLLEPKPQ-GCYLVRFSESAVTFVLSYRSRTCCRHFLLAQLrdGRHVVLGEdSAHARLQDLLLHY 77
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
798-846 1.01e-05

Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212939 [Multi-domain]  Cd Length: 56  Bit Score: 44.27  E-value: 1.01e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG---DYGGKKqlWFPSNYV 846
Cdd:cd12006     5 ALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEArslTTGETG--YIPSNYV 54
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
541-643 1.01e-05

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 45.68  E-value: 1.01e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  541 STELHSNEKWFHGKLGagrdgRHIAERLLTeycieTGA-PDGSFLVRESETfVGDYTLSFWRNGKVQHCRIhSRQDAGtp 619
Cdd:cd10402     3 ATTAHERMPWYHGSIA-----RDEAERRLY-----SGAqPDGKFLLRERKE-SGTYALSLVYGKTVYHYRI-DQDKSG-- 68
                          90       100
                  ....*....|....*....|....
gi 530418161  620 KFFLTDNLVFDSLYDLITHYQQVP 643
Cdd:cd10402    69 KYSIPEGTKFDTLWQLVEYLKLKP 92
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
544-640 1.14e-05

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 45.67  E-value: 1.14e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  544 LHSNEKWFHGKLGagrdgRHIAERLLteycIETGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFL 623
Cdd:cd10413     1 IHRTQPWFHGRIS-----REESQRLI----GQQGLVDGVFLVRESQRNPQGFVLSLCHLQKVKHYLILPSEEEGRLYFSM 71
                          90
                  ....*....|....*...
gi 530418161  624 TDNLV-FDSLYDLITHYQ 640
Cdd:cd10413    72 DDGQTrFTDLLQLVEFHQ 89
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
796-848 1.19e-05

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212727 [Multi-domain]  Cd Length: 55  Bit Score: 43.86  E-value: 1.19e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGD--YGGKKQlWFPSNYVEE 848
Cdd:cd11793     2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERG-WFPSSYTEE 55
SH3_PACSIN3 cd11997
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); ...
796-847 1.22e-05

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); PACSIN 3 or Syndapin III (Synaptic dynamin-associated protein III) is expressed ubiquitously and regulates glucose uptake in adipocytes through its role in GLUT1 trafficking. It also modulates the subcellular localization and stimulus-specific function of the cation channel TRPV4. PACSINs act as regulators of cytoskeletal and membrane dynamics. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212930 [Multi-domain]  Cd Length: 56  Bit Score: 43.80  E-value: 1.22e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTF-IKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:cd11997     4 VRALYDYTGQEADELSFkAGEELLKIGEEDEQGWCKGRLLSGRIGLYPANYVE 56
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
548-641 1.25e-05

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 45.40  E-value: 1.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLTeycietgAP---DGSFLVRESETFVGDYTLS---FWRNGKV-QHCRIHSRQDAGtpk 620
Cdd:cd10371     3 EKWFFRTIS-----RKDAERQLL-------APmnkAGSFLIRESESNKGAFSLSvkdVTTQGEVvKHYKIRSLDNGG--- 67
                          90       100
                  ....*....|....*....|.
gi 530418161  621 FFLTDNLVFDSLYDLITHYQQ 641
Cdd:cd10371    68 YYISPRITFPTLQALVQHYSK 88
SH3_Intersectin1_4 cd11993
Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
802-852 1.28e-05

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212926  Cd Length: 65  Bit Score: 43.95  E-value: 1.28e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  802 YKAQREDELTFIKSAIIQNVEKQEGGWWRGDY---GGKKQL-WFPSNYVeEMVNP 852
Cdd:cd11993    12 YTATGPEQLTLAPGQLILIRKKNPGGWWEGELqarGKKRQIgWFPANYV-KLLSP 65
SH3_Lasp1_C cd11934
C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic ...
797-849 1.30e-05

C-terminal Src Homology 3 domain of LIM and SH3 domain protein 1; Lasp1 is a cytoplasmic protein that binds focal adhesion proteins and is involved in cell signaling, migration, and proliferation. It is overexpressed in several cancer cells including breast, ovarian, bladder, and liver. In cancer cells, it can be found in the nucleus; its degree of nuclear localization correlates with tumor size and poor prognosis. Lasp1 is a 36kD protein containing an N-terminal LIM domain, two nebulin repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212867 [Multi-domain]  Cd Length: 59  Bit Score: 43.83  E-value: 1.30e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG--DYGGKKQLwFPSNYVEEM 849
Cdd:cd11934     6 RAVYDYNAADEDEVSFQDGDTIVNVQQIDDGWMYGtvERTGDTGM-LPANYVEAI 59
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
528-642 1.32e-05

N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198216  Cd Length: 103  Bit Score: 45.21  E-value: 1.32e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  528 GNEDEEEPKEVSSSTELHSneKWFHGKLGagrdgRHIAERLLTEycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQH 607
Cdd:cd10353     1 GPEYEEEEVAIPLTAPPTN--QWYHGRLD-----RTIAEERLRQ-----AGKLGSYLIRESDRRPGSFVLSFLSRTGVNH 68
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 530418161  608 CRIhsrqDAGTPKFFLTDNLvFDSLYDLITHYQQV 642
Cdd:cd10353    69 FRI----IAMCGDYYIGGRR-FSSLSDLIGYYSHV 98
SH3_Tks_2 cd12016
Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
802-847 1.35e-05

Second Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the second SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212949 [Multi-domain]  Cd Length: 54  Bit Score: 43.60  E-value: 1.35e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 530418161  802 YKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGkKQLWFPSNYVE 847
Cdd:cd12016     9 YKAENEDEIGFETGVVVEVIQKNLDGWWKIRYQG-KEGWAPATYLK 53
SH3_PACSIN_like cd11999
Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C ...
796-847 1.58e-05

Src homology 3 domain of an unknown subfamily of proteins with similarity to Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212932 [Multi-domain]  Cd Length: 56  Bit Score: 43.39  E-value: 1.58e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQ-EGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:cd11999     4 VRAVYDYTGQEPDELSFKAGEELLKVEDEdEQGWCKGVTDGGAVGLYPANYVE 56
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
668-746 1.81e-05

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 44.88  E-value: 1.81e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLmRVPRDGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQEGQTVML---GNSEFDSLVDLISYYEKH 744
Cdd:cd10417     9 WFHGFITRKQTEQLL-RDKALGSFLIRLSDRATGYILSYRGSDRCRHFVINQLRNRRYLisgDTSSHSTLAELVRHYQEV 87

                  ..
gi 530418161  745 PL 746
Cdd:cd10417    88 QL 89
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
798-846 1.88e-05

Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212940 [Multi-domain]  Cd Length: 58  Bit Score: 43.48  E-value: 1.88e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG-DYGGKKQLWFPSNYV 846
Cdd:cd12007     5 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEArSIATGKNGYIPSNYV 54
SH3_GRAF3 cd12066
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is ...
797-847 2.04e-05

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity to GRAF and GRAF2. It contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212999  Cd Length: 55  Bit Score: 43.13  E-value: 2.04e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQ-EGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd12066     3 KAMYSCKAEHSHELSFPQGAIFSNVYPSvEPGWLKATYEGKTGL-VPENYVV 53
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
796-847 2.30e-05

Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called SSU81 (Suppressor of SUA8-1 mutation), is a yeast membrane protein that regulates adaptation to high salt conditions by activating the HOG (high-osmolarity glycerol) pathway. High salt concentrations lead to the localization to the membrane of the MAPKK Pbs2, which is then activated by the MAPKK Ste11 and in turn, activates the MAPK Hog1. Pbs2 is localized to the membrane though the interaction of its PxxP motif with the SH3 domain of Sho1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212789 [Multi-domain]  Cd Length: 55  Bit Score: 43.18  E-value: 2.30e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  796 VKALFDYKAQRED--ELTFIKSAIIQnVEKQEGGWWRGDYGGKKQLWFPSNYVE 847
Cdd:cd11855     2 ARALYPYDASPDDpnELSFEKGEILE-VSDTSGKWWQARKSNGETGICPSNYLQ 54
SH3_Intersectin1_1 cd11987
First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
797-848 2.46e-05

First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212920 [Multi-domain]  Cd Length: 55  Bit Score: 43.06  E-value: 2.46e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11987     3 RALYPFEARSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTG-WFPANYAEK 55
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
796-848 2.47e-05

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212692 [Multi-domain]  Cd Length: 55  Bit Score: 43.12  E-value: 2.47e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEE 848
Cdd:cd11758     3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNARNSEGKTGMIPVPYVEK 55
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
577-639 2.66e-05

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 44.39  E-value: 2.66e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530418161  577 GAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHS-RQDAGTPKFFLTDNLVFDSLYDLITHY 639
Cdd:cd09926    25 GQRHGVFLVRDSSTIPGDYVLSVSENSRVSHYIINSlGQPAPNQSRYRIGDQEFDDLPALLEFY 88
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
42-142 3.20e-05

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) consists of three family members, delta 1, 2, and 3. PLC-delta1 is the most well studied. PLC-delta is activated by high calcium levels generated by other PLC family members, and functions as a calcium amplifier within the cell. PLC-delta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. The PH domain binds PIP2 and promotes activation of the catalytic core as well as tethering the enzyme to the plasma membrane. The C2 domain has been shown to mediate calcium-dependent phospholipid binding as well. The PH and C2 domains operate in concert as a "tether and fix" apparatus necessary for processive catalysis by the enzyme. Its leucine-rich nuclear export signal (NES) in its EF hand motif, as well as a Nuclear localization signal within its linker region allow PLC-delta 1 to actively translocate into and out of the nucleus. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270169  Cd Length: 117  Bit Score: 44.62  E-value: 3.20e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161   42 KSQRPeRKTFQVKLETRQITWSRGADKIEGAID----IREIKEIRPGKTSRDFDRYQEdpAFRPDQshCFVILYgmEFRL 117
Cdd:cd13363    11 RSRSW-KKERFYKLQEDCKTVWHESKKTRSNSKqtfsIEDIESVREGHQSEGLRKYAE--AFPEDR--CFSIVF--KGRR 83
                          90       100
                  ....*....|....*....|....*
gi 530418161  118 KTLSLQATSEDEVNMWIKGLTWLME 142
Cdd:cd13363    84 KNLDLIAPSEEEAQRWVRGLEKLIA 108
SH3_NoxO1_2 cd12024
Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox ...
794-837 3.75e-05

Second or C-terminal Src homology 3 domain of NADPH oxidase (Nox) Organizing protein 1; Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1 is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. NoxO1 contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of NoxO1. The tandem SH3 domains of NoxO1 interact with the PRR of p22phox, which also complexes with Nox1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212957  Cd Length: 53  Bit Score: 42.32  E-value: 3.75e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 530418161  794 CAVKAlfdYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKK 837
Cdd:cd12024     3 YATRA---YEAQKEDELSVPAGVVVEVLQKSDNGWWLIRYNGRA 43
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
668-756 3.81e-05

Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198252  Cd Length: 97  Bit Score: 43.93  E-value: 3.81e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHmLMRVPRDGAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSE--FDSLVDLISYYEKH 744
Cdd:cd10389     3 WYHGAISRGDAEN-LLRLCKECSYLVRnSQTSKHDYSLSLKSNQGFMHMKLAKTKEKYVLGQNSppFDSVPEVIHYYTTR 81
                          90
                  ....*....|....*.
gi 530418161  745 PLYRK----MKLRYPI 756
Cdd:cd10389    82 KLPIKgaehLSLLYPV 97
SH2_SHD cd10390
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ...
668-756 4.30e-05

Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression of SHD is restricted to the brain. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198253  Cd Length: 98  Bit Score: 43.53  E-value: 4.30e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHmLMRVPRDGAFLVR-KRNEPNSYAISFRAEGKIKHCRV--QQEGQTVMLGNS-EFDSLVDLISYYEK 743
Cdd:cd10390     3 WFHGPLSRADAEN-LLSLCKEGSYLVRlSETRPQDCSLSLRSSQGFLHLKFarTRENQVVLGQHSgPFPSVPELVLHYSS 81
                          90
                  ....*....|....*..
gi 530418161  744 HPL----YRKMKLRYPI 756
Cdd:cd10390    82 RPLpvqgAEHLALLYPV 98
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
668-755 4.60e-05

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198213  Cd Length: 103  Bit Score: 43.77  E-value: 4.60e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVpRDGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQEGQTV-MLGNSEFD--SLVDLISYYEKH 744
Cdd:cd10350     9 WFHGILTLKKANELLLST-MPGSFLIRVSEKIKGYALSYLSEEGCKHFLIDASADSYsFLGVDQLQhaTLADLVEYHKEE 87
                          90
                  ....*....|...
gi 530418161  745 PLYR--KMKLRYP 755
Cdd:cd10350    88 PITSlgKELLLYP 100
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
665-755 4.71e-05

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198221  Cd Length: 100  Bit Score: 43.58  E-value: 4.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  665 SKEWYHASLTRAQAEHMLMRVPRD-GAFLVRKRNEPNS-YAISFRAEGKIKHCRV--QQEGQTVMLGNSEFDSLVDLISY 740
Cdd:cd10358     1 SEPWFFGCISRSEAVRRLQAEGNAtGAFLIRVSEKPSAdYVLSVRDTQAVRHYKIwrRAGGRLHLNEAVSFLSLPELVNY 80
                          90
                  ....*....|....*
gi 530418161  741 YEKHPLYRKMKLRYP 755
Cdd:cd10358    81 HRAQSLSHGLRLAAP 95
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
668-743 5.11e-05

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198214  Cd Length: 103  Bit Score: 43.72  E-value: 5.11e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530418161  668 WYHASLTRAQAEHMLMRVPrDGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQEGQTV-MLG--NSEFDSLVDLISYYEK 743
Cdd:cd10351     9 WFHGIISREEAEALLMNAT-EGSFLVRVSEKIWGYTLSYRLQSGFKHFLVDASGDFYsFLGvdPNRHATLTDLIDFHKE 86
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
581-639 6.04e-05

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 42.64  E-value: 6.04e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 530418161  581 GSFLVRESETFVGDYTLSFWRNGKVQHCRIhSRQDAGTpkFFLTDNLVFDSLYDLITHY 639
Cdd:cd10360    24 GAFLIRPSESSLGGYSLSVRAQAKVCHYRI-CMAPSGS--LYLQKGRLFPGLEELLAYY 79
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
796-848 6.31e-05

Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. This subfamily consists of SH3 domain containing SNXs including SNX9, SNX18, SNX33, and similar proteins. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212697 [Multi-domain]  Cd Length: 55  Bit Score: 41.93  E-value: 6.31e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  796 VKALFDYKAQREDELTF----IKSAIIQNVekqEGGWWRGDYGGKKQLWFPSNYVEE 848
Cdd:cd11763     2 VRALYDFDSQPSGELSLrageVLTITRQDV---GDGWLEGRNSRGEVGLFPSSYVEI 55
SH2_SH2B1 cd10410
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, ...
667-746 6.42e-05

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, PSM), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198273  Cd Length: 97  Bit Score: 43.08  E-value: 6.42e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  667 EWYHASLTRAQAEHMLMR--VPRDGAFLVRK-RNEPNSYAISFRAEGKIKHCR--VQQEGQtVMLGNSEFDSLVDLISYY 741
Cdd:cd10410     9 PWFHGMLSRLKAAQLVLEggTGSHGVFLVRQsETRRGEYVLTFNFQGKAKHLRlsLNEEGQ-CRVQHLWFQSIFDMLEHF 87

                  ....*
gi 530418161  742 EKHPL 746
Cdd:cd10410    88 RVHPI 92
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
544-640 7.88e-05

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198278  Cd Length: 108  Bit Score: 43.09  E-value: 7.88e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  544 LHSNEKWFHGKLGAGRDGRHIAERllteycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAGTPKFFL 623
Cdd:cd10415     1 IHRTQHWFHGRISREESHRIIKQQ---------GLVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFQILPCEDDGQTFFSL 71
                          90
                  ....*....|....*...
gi 530418161  624 TD-NLVFDSLYDLITHYQ 640
Cdd:cd10415    72 DDgNTKFSDLIQLVDFYQ 89
SH3_Intersectin1_2 cd11989
Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
797-847 8.18e-05

Second Src homology 3 domain (or SH3B) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212922 [Multi-domain]  Cd Length: 52  Bit Score: 41.62  E-value: 8.18e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEgGWWRGDYGGKKQlWFPSNYVE 847
Cdd:cd11989     3 QALYPWRAKKDNHLNFNKNDVITVLEQQD-MWWFGEVQGQKG-WFPKSYVK 51
SH3_Tks5_4 cd12019
Fourth Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ...
802-848 8.51e-05

Fourth Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the fourth SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212952  Cd Length: 53  Bit Score: 41.50  E-value: 8.51e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 530418161  802 YKAQREDELTFIKSAIIQNVEKQEGGWWRGDYgGKKQLWFPSNYVEE 848
Cdd:cd12019     8 YQKVQDSEISFPAGVEVEVLEKQESGWWYVRF-GELEGWAPSHYLEL 53
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
797-846 9.09e-05

Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also called Spermatogenesis-associated protein 13 (SPATA13), is a GEF that localizes with actin at the leading edge of cells and is important in cell migration and adhesion dynamics. GEFs activate small GTPases by exchanging bound GDP for free GTP. ASEF2 can activate both Rac 1 and Cdc42, but only Rac1 activation is necessary for increased cell migration and adhesion turnover. Together with APC (adenomatous polyposis coli) and Neurabin2, a scaffold protein that binds F-actin, it is involved in regulating HGF-induced cell migration. ASEF2 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212907  Cd Length: 54  Bit Score: 41.20  E-value: 9.09e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDyGGKKQLWFPSNYV 846
Cdd:cd11974     4 EALWDHVTMDDQELAFKAGDVIRVLEASNKDWWWGR-NEDREAWFPASFV 52
SH3_SH3RF_1 cd11786
First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model ...
794-847 9.96e-05

First Src Homology 3 domain of SH3 domain containing ring finger proteins; This model represents the first SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212720 [Multi-domain]  Cd Length: 53  Bit Score: 41.19  E-value: 9.96e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  794 CAvKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGkKQLWFPSNYVE 847
Cdd:cd11786     1 CA-KALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNG-KQGFFPASYVQ 52
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
798-846 1.06e-04

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The N-terminal SH3 domain of GRB2 binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212738 [Multi-domain]  Cd Length: 52  Bit Score: 41.19  E-value: 1.06e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  798 ALFDYKAQREDELTFIKSAI--IQNVEKQEgGWWRGDYGGKKQlWFPSNYV 846
Cdd:cd11804     4 AKHDFKATAEDELSFKKGSIlkVLNMEDDP-NWYKAELDGKEG-LIPKNYI 52
SH3_GRAF cd12064
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also ...
797-847 1.08e-04

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212997  Cd Length: 56  Bit Score: 41.25  E-value: 1.08e-04
                          10        20        30        40        50
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gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNV-EKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd12064     4 KALYACKAEHDSELSFTAGTVFDNVhPSQEPGWLEGTLNGKTGL-IPENYVE 54
SH3_Sla1p_1 cd11773
First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
796-830 1.15e-04

First Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212707 [Multi-domain]  Cd Length: 57  Bit Score: 41.26  E-value: 1.15e-04
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWR 830
Cdd:cd11773     2 YKALYDYEPQTEDELTIQEDDILYLLEKSDDDWWK 36
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
797-848 1.26e-04

First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the first SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212715 [Multi-domain]  Cd Length: 53  Bit Score: 40.79  E-value: 1.26e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd11781     3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGI-FPASYVEI 53
SH3_Sorbs_3 cd11780
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) ...
797-848 1.27e-04

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the third SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212714 [Multi-domain]  Cd Length: 55  Bit Score: 40.75  E-value: 1.27e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQL-WFPSNYVEE 848
Cdd:cd11780     3 RALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGTSERTGLFgTFPGNYVAR 55
SH3_Nebulin_C cd11933
C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 ...
796-849 1.41e-04

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212866 [Multi-domain]  Cd Length: 58  Bit Score: 41.15  E-value: 1.41e-04
                          10        20        30        40        50
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG--DYGGKKQLwFPSNYVEEM 849
Cdd:cd11933     4 FRAMYDYRAADDDEVSFKDGDTIVNVQTIDEGWMYGtvQRTGKTGM-LPANYVEAI 58
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
795-849 1.50e-04

Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms (A1, A2, and A3). Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212737 [Multi-domain]  Cd Length: 55  Bit Score: 40.71  E-value: 1.50e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 530418161  795 AVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEEM 849
Cdd:cd11803     2 CCRALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGF-FPVNYVEVL 55
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
796-848 1.69e-04

C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, also called Neutrophil cytosol factor 2 (NCF-2), is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p67phox plays a regulatory role and contains N-terminal TPR, first SH3 (or N-terminal or central SH3), PB1, and C-terminal SH3 domains. It binds, via its C-terminal SH3 domain, to a proline-rich region of p47phox and upon activation, this complex assembles with flavocytochrome b558, the Nox2-p22phox heterodimer. Concurrently, RacGTP translocates to the membrane and interacts with the TPR domain of p67phox, which leads to the activation of NADPH oxidase. The PB1 domain of p67phox binds to its partner PB1 domain in p40phox, and this facilitates the assembly of p47phox-p67phox at the membrane. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212979  Cd Length: 53  Bit Score: 40.56  E-value: 1.69e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVEE 848
Cdd:cd12046     2 VVALFSYEASQPEDLEFQKGDVILVLSKVNEDWLEGQCKGKIGI-FPSAFVED 53
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
549-659 1.70e-04

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 42.19  E-value: 1.70e-04
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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  549 KWFHGKLGagrdgRHIAERLLTEYCIetgapdGSFLVRESETFVGdYTLSFWRNGKVQHCRIHSRQDAgtpKFFLT-DNL 627
Cdd:cd10417     8 PWFHGFIT-----RKQTEQLLRDKAL------GSFLIRLSDRATG-YILSYRGSDRCRHFVINQLRNR---RYLISgDTS 72
                          90       100       110
                  ....*....|....*....|....*....|..
gi 530418161  628 VFDSLYDLITHYQQVPLrcNEFEMRLSEPVPQ 659
Cdd:cd10417    73 SHSTLAELVRHYQEVQL--EPFGETLTAACPR 102
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
580-644 1.77e-04

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 42.30  E-value: 1.77e-04
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gi 530418161  580 DGSFLVRESETFVGD--YTLSFWRNGKVQHCRIhsRQDAGTPKFFLTDNL----VFDSLYDLITHYQQVPL 644
Cdd:cd09929    33 DGTFLVRDSSGKDSSqpYTLMVLYNDKVYNIQI--RFLENTRQYALGTGLrgeeTFSSVAEIIEHHQKTPL 101
SH2_STAP1 cd10403
Src homology 2 domain found in Signal-transducing adaptor protein 1 (STAP1); STAP1 is a ...
672-743 1.78e-04

Src homology 2 domain found in Signal-transducing adaptor protein 1 (STAP1); STAP1 is a signal-transducing adaptor protein. It is composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. STAP-1 is an ortholog of BRDG1 (BCR downstream signaling 1). STAP1 protein functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor signaling. The protein is phosphorylated by Tec and participates in a positive feedback loop, increasing Tec activity. STAP1 has been shown to interact with C19orf2, an unconventional prefoldin RPB5 interactor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198266  Cd Length: 94  Bit Score: 41.63  E-value: 1.78e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  672 SLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISFRAE---GKIKHCRVQQEGQ--TVMLGNS-EFDSLVDLISYYEK 743
Cdd:cd10403     6 KVSRKEAEELLERNPSCGNMLLRPGSDSSNYSITTRQEinkPRIKHYRVMSRGQgyTIELEKPvTCPTLHDVINYFVE 83
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
797-846 1.81e-04

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 40.57  E-value: 1.81e-04
                          10        20        30        40        50
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gi 530418161  797 KALFDYKAQREDE-LTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYV 846
Cdd:cd11829     3 RTLYAFTGEQHQQgLSFEAGELIRVLQAPDGGWWEGEKDGLRG-WFPASYV 52
SH3_Sorbs1_3 cd11916
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), ...
797-847 1.88e-04

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; Sorbs1 is also called ponsin, SH3P12, or CAP (c-Cbl associated protein). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It binds Cbl and plays a major role in regulating the insulin signaling pathway by enhancing insulin-induced phosphorylation of Cbl. Sorbs1, like vinexin, localizes at cell-ECM and cell-cell adhesion sites where it binds vinculin, paxillin, and afadin. It may function in the control of cell motility. Other interaction partners of Sorbs1 include c-Abl, Sos, flotillin, Grb4, ataxin-7, filamin C, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212849 [Multi-domain]  Cd Length: 59  Bit Score: 40.75  E-value: 1.88e-04
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gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQL-WFPSNYVE 847
Cdd:cd11916     5 QALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSRRTKQFgTFPGNYVK 56
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
796-847 1.91e-04

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212724 [Multi-domain]  Cd Length: 64  Bit Score: 40.77  E-value: 1.91e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 530418161  796 VKALFDYKAQREDELTFIKSAII-----QNVEKQEGGWWRG--DYGGKKQLwFPSNYVE 847
Cdd:cd11790     5 VRATHDYTAEDTDELTFEKGDVIlvipfDDPEEQDEGWLMGvkESTGCRGV-FPENFTE 62
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
796-845 2.24e-04

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing proteins; ASAPs are Arf GTPase activating proteins (GAPs) and they function in regulating cell growth, migration, and invasion. They contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3, but some ASAP3 proteins do not seem to harbor a C-terminal SH3 domain. ASAP1 and ASAP2 show GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but are able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212755 [Multi-domain]  Cd Length: 53  Bit Score: 39.99  E-value: 2.24e-04
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                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGK--KQLWFPSNY 845
Cdd:cd11821     2 VRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDpsRRGVFPVSF 53
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
798-846 2.42e-04

Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The third SH3 domain (SH3C) of ITSN2 has been shown to bind the K15 protein of Kaposi's sarcoma-associated herpesvirus. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212925  Cd Length: 52  Bit Score: 39.99  E-value: 2.42e-04
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQnVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11992     4 ALYPYSSSEPGDLTFNEGEEIL-VTQKDGEWWTGSIEDRTGI-FPSNYV 50
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
796-845 2.66e-04

Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212751 [Multi-domain]  Cd Length: 50  Bit Score: 39.77  E-value: 2.66e-04
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNY 845
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGI-FPRAF 50
SH3_Lyn cd12004
Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of ...
796-849 2.74e-04

Src homology 3 domain of Lyn Protein Tyrosine Kinase; Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212937 [Multi-domain]  Cd Length: 56  Bit Score: 39.98  E-value: 2.74e-04
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEkQEGGWWRG-DYGGKKQLWFPSNYVEEM 849
Cdd:cd12004     2 VVALYPYDGIHEDDLSFKKGEKLKVIE-EHGEWWKArSLTTKKEGFIPSNYVAKV 55
SH3_Tks5_2 cd12077
Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also ...
802-848 2.77e-04

Second Src homology 3 domain of Tyrosine kinase substrate with five SH3 domains; Tks5, also called SH3 and PX domain-containing protein 2A (SH3PXD2A) or Five SH (FISH), is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. It binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. Tks5 contains an N-terminal Phox homology (PX) domain and five SH3 domains. This model characterizes the second SH3 domain of Tks5. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213010  Cd Length: 54  Bit Score: 40.02  E-value: 2.77e-04
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gi 530418161  802 YKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd12077     9 YTSQGKDEIGFEKGVTVEVIQKNLEGWWYIRYLGKEG-WAPASYLKK 54
PH pfam00169
PH domain; PH stands for pleckstrin homology.
71-142 2.84e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 41.39  E-value: 2.84e-04
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gi 530418161    71 GAIDIREIKEIRPGKTSRdfdryqedpafrPDQSHCFVILYGMEFRLKTLSLQATSEDEVNMWIKGLTWLME 142
Cdd:pfam00169   46 GSISLSGCEVVEVVASDS------------PKRKFCFELRTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
798-846 2.99e-04

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212991 [Multi-domain]  Cd Length: 58  Bit Score: 39.92  E-value: 2.99e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQ-----EGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd12058     4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGI-FPANYV 56
SH3_GRB2_N cd11946
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
798-847 3.17e-04

N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. Its N-terminal SH3 domain binds to Sos and Sos-derived proline-rich peptides. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212879 [Multi-domain]  Cd Length: 56  Bit Score: 40.01  E-value: 3.17e-04
                          10        20        30        40        50
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNV-EKQEGGWWRGDYGGKKQlWFPSNYVE 847
Cdd:cd11946     5 AKYDFKATADDELSFKRGDILKVLnEECDQNWYKAELNGKDG-FIPKNYIE 54
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
663-742 3.84e-04

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 41.05  E-value: 3.84e-04
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gi 530418161  663 HESKEWYHASLTRAQAEHMLMRVPR-DGAFLVR--KRNePNSYAISFRAEGKIKHCRV---QQEGQ---TVMLGNSEFDS 733
Cdd:cd10413     2 HRTQPWFHGRISREESQRLIGQQGLvDGVFLVResQRN-PQGFVLSLCHLQKVKHYLIlpsEEEGRlyfSMDDGQTRFTD 80

                  ....*....
gi 530418161  734 LVDLISYYE 742
Cdd:cd10413    81 LLQLVEFHQ 89
PI-PLCc_Rv2075c_like cd08590
Catalytic domain of uncharacterized Mycobacterium tuberculosis Rv2075c-like proteins; This ...
321-494 4.08e-04

Catalytic domain of uncharacterized Mycobacterium tuberculosis Rv2075c-like proteins; This subfamily corresponds to the catalytic domain present in uncharacterized Mycobacterium tuberculosis Rv2075c and its homologs. Members in this family are more closely related to the Streptomyces antibioticus phosphatidylinositol-specific phospholipase C1(SaPLC1)-like proteins rather than the typical bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), which participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). In contrast, SaPLC1-like proteins have two Ca2+-chelating amino acid substitutions which convert them to metal-dependent bacterial PI-PLC. Rv2075c and its homologs have the same amino acid substitutions as well, which might suggest they have metal-dependent PI-PLC activity.


Pssm-ID: 176532  Cd Length: 267  Bit Score: 43.55  E-value: 4.08e-04
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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  321 TMNNPLSHYWISSSHNTYLTgdqfSSESSLEAYARC--------------LRMGCRCIELDCWDGPDGMPVIyHGHTL-- 384
Cdd:cd08590     5 DSNAPLCQAQILGTHNSYNS----RAYGYGNRYHGVryldpnqelsitdqLDLGARFLELDVHWTTGDLRLC-HGGDHgy 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  385 -----TTKIKFSDVLHTIKEhaFVAS--EYPVILSIEDHCSIAQQRNMAQYFKKVLGDTLLTKPVeiSADGLPSPNQLKR 457
Cdd:cd08590    80 lgvcsSEDRLFEDGLNEIAD--WLNAnpDEVVILYLEDHGDGGKDDELNALLNDAFGDLLYTPSD--CDDLQGLPNWPTK 155
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 530418161  458 KILIKHKK----LAEGSAYEEVPTSMMYSENDISNSIKNGI 494
Cdd:cd08590   156 EDMLNSGKqvvlATGGGCSGAQGMYNRKEFADTQPSNFRPY 196
SH2_SOCS6 cd10387
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
558-638 4.60e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198250  Cd Length: 100  Bit Score: 40.59  E-value: 4.60e-04
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gi 530418161  558 GRDGRHIAERLLTEycietgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRI-HSrqdAGTPKFF-LTDNLVFDSLYDL 635
Cdd:cd10387    15 GPITRWEAEGKLAN------VPDGSFLVRDSSDDRYLLSLSFRSHGKTLHTRIeHS---NGRFSFYeQPDVEGHTSIVDL 85

                  ...
gi 530418161  636 ITH 638
Cdd:cd10387    86 IEH 88
SH3_Src cd12008
Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or ...
798-846 4.83e-04

Src homology 3 domain of Src Protein Tyrosine Kinase; Src (or c-Src) is a cytoplasmic (or non-receptor) PTK and is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212941  Cd Length: 56  Bit Score: 39.32  E-value: 4.83e-04
                          10        20        30        40        50
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGD-YGGKKQLWFPSNYV 846
Cdd:cd12008     4 ALYDYESRTETDLSFKKGERLQIVNNTEGDWWLAHsLTTGQTGYIPSNYV 53
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
664-755 5.82e-04

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 40.72  E-value: 5.82e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  664 ESKEWYHASLTRAQAEHMLMrVPRD--GAFLVR-KRNEPNSYAISFR-----AEGKIKHCRVQ--QEGQTVMLGNSEFDS 733
Cdd:cd10363     1 ETEEWFFKGISRKDAERQLL-APGNmlGSFMIRdSETTKGSYSLSVRdydpqHGDTVKHYKIRtlDNGGFYISPRSTFST 79
                          90       100
                  ....*....|....*....|..
gi 530418161  734 LVDLISYYEKHPLYRKMKLRYP 755
Cdd:cd10363    80 LQELVDHYKKGNDGLCQKLSVP 101
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
798-846 5.86e-04

Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating Proteins (srGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of srGAPs (srGAP1-3), all of which are expressed during embryonic and early development in the nervous system but with different localization and timing. A fourth member has also been reported (srGAP4, also called ARHGAP4). srGAPs contain an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212743 [Multi-domain]  Cd Length: 53  Bit Score: 38.92  E-value: 5.86e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11809     4 AQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGL-VPHKYI 51
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
565-631 7.05e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198251  Cd Length: 101  Bit Score: 40.42  E-value: 7.05e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418161  565 AERLLTEYcietgaPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIhsRQDAGTPKFFLTDNLVFDS 631
Cdd:cd10388    22 AEKVLSNK------PDGSFLVRDSSDDRYIFSLSFRSQGSVHHTRI--EQYQGTFSLGSRNKFVDRS 80
SH3_Shank1 cd11982
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also ...
795-846 8.28e-04

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines. Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning. Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212915 [Multi-domain]  Cd Length: 52  Bit Score: 38.45  E-value: 8.28e-04
                          10        20        30        40        50
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gi 530418161  795 AVKAlfdYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYV 846
Cdd:cd11982     5 AVKP---YQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVG-WFPSDCV 52
SH3_CASS4 cd12000
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; ...
797-844 8.55e-04

Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212933  Cd Length: 57  Bit Score: 38.71  E-value: 8.55e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 530418161  797 KALFDYKAQREDELTFIKSAII----QNVEKQEgGWWRGDYGGKKQLwFPSN 844
Cdd:cd12000     4 RALYDNKADCSDELAFRRGDILtvleQNVPGSE-GWWKCLLHGRQGL-APAN 53
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
548-644 8.94e-04

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198213  Cd Length: 103  Bit Score: 39.91  E-value: 8.94e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  548 EKWFHGKLGagrdgRHIAERLLTeycieTGAPdGSFLVRESETFVGdYTLSFWRNGKVQHCRIHSRQDAGTpkFFLTDNL 627
Cdd:cd10350     7 APWFHGILT-----LKKANELLL-----STMP-GSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASADSYS--FLGVDQL 72
                          90
                  ....*....|....*..
gi 530418161  628 VFDSLYDLITHYQQVPL 644
Cdd:cd10350    73 QHATLADLVEYHKEEPI 89
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
863-931 8.94e-04

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 39.84  E-value: 8.94e-04
                            10        20        30        40        50        60        70
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gi 530418161    863 DENSPLGDLLRGVLDVPACQIAIRPEGKN-NRLFVFSISMASvaHWSLDVAADSQEELQDWVKKIREVAQ 931
Cdd:smart00233   35 SKKDKKSYKPKGSIDLSGCTVREAPDPDSsKKPHCFEIKTSD--RKTLLLQAESEEEREKWVEALRKAIA 102
SH3_Nephrocystin cd11770
Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain ...
796-848 1.07e-03

Src Homology 3 domain of Nephrocystin (or Nephrocystin-1); Nephrocystin contains an SH3 domain involved in signaling pathways that regulate cell adhesion and cytoskeletal organization. It is a protein that in humans is associated with juvenile nephronophthisis, an inherited kidney disease characterized by renal fibrosis that lead to chronic renal failure in children. It is localized in cell-cell junctions in renal duct cells, and is known to interact with Ack1, an activated Cdc42-associated kinase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212704 [Multi-domain]  Cd Length: 54  Bit Score: 38.45  E-value: 1.07e-03
                          10        20        30        40        50
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG-DYGGKKQLwFPSNYVEE 848
Cdd:cd11770     2 YEALSDFQAEQEGDLSFKKGEVLRIISKRADGWWLAeNSKGNRGL-VPKTYLKV 54
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
797-847 1.17e-03

Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called Merlin-associated protein (MAP), RUN and SH3 domain-containing protein (RUSC3), RUN and TBC1 domain-containing protein 3 (RUTBC3), Rab GTPase-activating protein 5 (RabGAP5), or Rab GAP-like protein (RabGAPLP). It is expressed ubiquitously and functions as a regulator of small G protein RAP- and RAB-mediated neuronal signaling. It is involved in modulating NGF-mediated neurite outgrowth and differentiation. It also interacts with the tumor suppressor merlin and may play a role in the merlin-associated suppression of cell growth. SGSM3 contains TBC, SH3, and RUN domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212747  Cd Length: 53  Bit Score: 38.25  E-value: 1.17e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVE 847
Cdd:cd11813     3 KALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRG-WFPAKFVE 52
SH3_Vinexin_3 cd11918
Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain ...
797-846 1.21e-03

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212851 [Multi-domain]  Cd Length: 58  Bit Score: 38.40  E-value: 1.21e-03
                          10        20        30        40        50
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gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQL-WFPSNYV 846
Cdd:cd11918     5 KAVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGVSRRTQKFgTFPGNYV 55
SH3_FCHSD_1 cd11761
First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
792-847 1.24e-03

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212695 [Multi-domain]  Cd Length: 57  Bit Score: 38.11  E-value: 1.24e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  792 FKCavKALFDYKAQREDELTFIKSAIIQNVEKQEG-GWWRG-DYGGKKQlWFPSNYVE 847
Cdd:cd11761     2 VTC--KVLYSYEAQRPDELTITEGEELEVIEDGDGdGWVKArNKSGEVG-YVPENYLQ 56
SH3_ARHGEF5_19 cd11940
Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ...
796-848 1.34e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19; ARHGEF5, also called ephexin-3 or TIM (Transforming immortalized mammary oncogene), is a potent activator of RhoA and it plays roles in regulating cell shape, adhesion, and migration. It binds to the SH3 domain of Src and is involved in regulating Src-induced podosome formation. ARHGEF19, also called ephexin-2 or WGEF (weak-similarity GEF), is highly expressed in the intestine, liver, heart and kidney. It activates RhoA, Cdc42, and Rac 1, and has been shown to activate RhoA in the Wnt-PCP (planar cell polarity) pathway. It is involved in the regulation of cell polarity and cytoskeletal reorganization. ARHGEF5 and ARHGEF19 contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212873  Cd Length: 55  Bit Score: 38.23  E-value: 1.34e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRG-DYGGKKQLWFPSNYVEE 848
Cdd:cd11940     2 VQCIRSYKAQENDELTLEKADIIMVRQQSSDGWLEGvRLSDGERGWFPQSHVEE 55
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
157-283 1.46e-03

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 40.66  E-value: 1.46e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  157 LRKQFYSVDRNREDRISAKDLKNMLSQvnyrvPNMRFLRE------RLTDLEqRSGDITYGQFAQLYRSLMysaqkTMDL 230
Cdd:cd16185     2 LRQWFRAVDRDRSGSIDVNELQKALAG-----GGLLFSLAtaekliRMFDRD-GNGTIDFEEFAALHQFLS-----NMQN 70
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  231 PFLEASTLRAGerpelcRVSLPEFQQFLLdYQGelWAVDRLQVQEFMLSFLRD 283
Cdd:cd16185    71 GFEQRDTSRSG------RLDANEVHEALA-ASG--FQLDPPAFQALFRKFDPD 114
SH2_SOCS3 cd10384
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
668-741 1.56e-03

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198247  Cd Length: 101  Bit Score: 39.34  E-value: 1.56e-03
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gi 530418161  668 WYHASLTRAQAEHMLMRVPrDGAFLVRKRNEPNS-YAISFRAEGKIKHCRVQQEGQTVML----GNSE----FDSLVDLI 738
Cdd:cd10384    12 FYWSTVSGKEANLLLSAEP-AGTFLIRDSSDQRHfFTLSVKTESGTKNLRIQCEGGSFSLqtdpRSTQpvprFDCVLKLV 90

                  ...
gi 530418161  739 SYY 741
Cdd:cd10384    91 HHY 93
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
797-846 1.59e-03

Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin and key regulatory proteins of the actin cytoskeleton. It plays an important role in regulating cell junction configuration. The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212730  Cd Length: 51  Bit Score: 37.72  E-value: 1.59e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11796     3 RVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGI-FPEGFV 51
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
798-845 1.60e-03

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212779 [Multi-domain]  Cd Length: 52  Bit Score: 37.56  E-value: 1.60e-03
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDY-GGKKQLWFPSNY 845
Cdd:cd11845     4 ALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARHlSTGKEGYIPSNY 52
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
795-845 1.70e-03

Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212885  Cd Length: 56  Bit Score: 37.99  E-value: 1.70e-03
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                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  795 AVKALFDYKAQREDELTFIKSAIIQNVEK--QEGGWWRGDYGGKKQlWFPSNY 845
Cdd:cd11952     2 VVYALWDYSAEFPDELSFKEGDMVTVLRKdgEGTDWWWASLCGREG-YVPRNY 53
SH3_Tks_3 cd12017
Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
801-848 1.74e-03

Third Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the third SH3 domain of Tks proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212950  Cd Length: 53  Bit Score: 37.82  E-value: 1.74e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 530418161  801 DYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd12017     7 EFQATIQDGISFQKGQKVEVIDKNPSGWWYVKIDGKEG-WAPSSYIEK 53
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
545-645 1.74e-03

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 39.22  E-value: 1.74e-03
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gi 530418161  545 HSNEKWFHGKLgagrdgrhiaERLLTEYCIeTGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpkFFLT 624
Cdd:cd10407     2 YSCQPWYAGAM----------ERLQAETEL-INRVNSTYLVRHRTKESGEYAISIKYNNEVKHIKILTRDGF----FHIA 66
                          90       100
                  ....*....|....*....|.
gi 530418161  625 DNLVFDSLYDLITHYQQVPLR 645
Cdd:cd10407    67 ENRKFKSLMELVEYYKHHSLK 87
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
797-846 1.77e-03

Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212750 [Multi-domain]  Cd Length: 51  Bit Score: 37.77  E-value: 1.77e-03
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                  ....*....|....*....|....*....|....*....|....*....|
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11816     3 VARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGI-FPLNFV 51
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
798-848 1.88e-03

C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212910 [Multi-domain]  Cd Length: 58  Bit Score: 37.68  E-value: 1.88e-03
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gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEG--GWWRGDYGGKKQlWFPSNYVEE 848
Cdd:cd11977     5 ARYNFAARDMRELSLREGDVVRIYSRIGGdqGWWKGETNGRIG-WFPSTYVEE 56
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
36-137 1.99e-03

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574  Cd Length: 102  Bit Score: 39.07  E-value: 1.99e-03
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gi 530418161     36 TLFYSKKSQRPERKTFQVKLETRQITW-----SRGADKIEGAIDIREIkEIRPGKTSRDFDRyqedpafrpdqSHCFVIL 110
Cdd:smart00233    6 WLYKKSGGGKKSWKKRYFVLFNSTLLYykskkDKKSYKPKGSIDLSGC-TVREAPDPDSSKK-----------PHCFEIK 73
                            90       100
                    ....*....|....*....|....*..
gi 530418161    111 YGMEfrlKTLSLQATSEDEVNMWIKGL 137
Cdd:smart00233   74 TSDR---KTLLLQAESEEEREKWVEAL 97
SH3_ephexin1 cd11939
Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called ...
796-848 2.18e-03

Src homology 3 domain of the Rho guanine nucleotide exchange factor, ephexin-1 (also called NGEF or ARHGEF27); Ephexin-1, also called NGEF (neuronal GEF) or ARHGEF27, activates RhoA, Tac1, and Cdc42 by exchanging bound GDP for free GTP. It is expressed mainly in the brain in a region associated with movement control. It regulates the stability of postsynaptic acetylcholine receptor (AChR) clusters and thus, plays a critical role in the maturation and neurotransmission of neuromuscular junctions. Ephexin-1 directly interacts with the ephrin receptor EphA4 and their coexpression enhances the ability of ephexin-1 to activate RhoA. It is required for normal axon growth and EphA-induced growth cone collapse. Ephexin-1 contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and SH3 domains. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212872 [Multi-domain]  Cd Length: 55  Bit Score: 37.62  E-value: 2.18e-03
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGD-YGGKKQLWFPSNYVEE 848
Cdd:cd11939     2 VQCVHPYVSQEPDELSLELADVLNILDKTDDGWIFGErLHDQERGWFPSSVVEE 55
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
667-741 2.24e-03

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 38.56  E-value: 2.24e-03
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gi 530418161  667 EWYHASLTRAQA-EHMLMRVPRDGAFLVR-KRNEPNSYAISFRAEGKIKHCRVQQEGQTVMLGNSE--FDSLVDLISYY 741
Cdd:cd10348     1 QWLHGALDRNEAvEILKQKADADGSFLVRySRRRPGGYVLTLVYENHVYHFEIQNRDDKWFYIDDGpyFESLEHLIEHY 79
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
796-846 2.26e-03

Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 (Cyk3 or Cyk3p) is a component of the actomyosin ring independent cytokinesis pathway in yeast. It interacts with Inn1 and facilitates its recruitment to the bud neck, thereby promoting cytokinesis. Cyk3p contains an N-terminal SH3 domain and a C-terminal transglutaminase-like domain. The Cyk3p SH3 domain binds to the C-terminal proline-rich region of Inn1. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212822  Cd Length: 53  Bit Score: 37.48  E-value: 2.26e-03
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gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDY-GGKKQLWFPSNYV 846
Cdd:cd11889     2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrRNGAEGIFPSNFV 53
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
550-639 2.81e-03

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 37.89  E-value: 2.81e-03
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gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietgAPDGSFLVRESETFVGdYTLSFWRNGKVQHCRIHSRQDAgtPKFFLTDNLVF 629
Cdd:cd10349     2 WFHGFIT-----RREAERLLEP------KPQGCYLVRFSESAVT-FVLSYRSRTCCRHFLLAQLRDG--RHVVLGEDSAH 67
                          90
                  ....*....|
gi 530418161  630 DSLYDLITHY 639
Cdd:cd10349    68 ARLQDLLLHY 77
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
797-847 2.85e-03

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212716 [Multi-domain]  Cd Length: 53  Bit Score: 36.94  E-value: 2.85e-03
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                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11782     3 RAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGI-FPVSYVQ 52
SH2_STAP_family cd09939
Src homology 2 domain found in Signal-transducing adaptor protein (STAP) family; STAP1 and ...
673-744 3.02e-03

Src homology 2 domain found in Signal-transducing adaptor protein (STAP) family; STAP1 and STAP2 are signal-transducing adaptor proteins. They are composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. STAP-1 is an ortholog of BRDG1 (BCR downstream signaling 1). STAP1 protein functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor signaling. The protein is phosphorylated by Tec and participates in a positive feedback loop, increasing Tec activity. STAP1 has been shown to interact with C19orf2, an unconventional prefoldin RPB5 interactor. The STAP2 protein is the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways. STAP2 has alternative splicing variants. STAP2 has been shown to interact with tyrosine-protein kinase 6 (PTK6). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198192  Cd Length: 94  Bit Score: 38.29  E-value: 3.02e-03
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gi 530418161  673 LTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISFRAE---GKIKHCRVQQEGQ--TVMLGNS-EFDSLVDLISYYEKH 744
Cdd:cd09939     7 VSRKEATELLERNPSCGNMLLRPGSDSRNYSVTTRQEiniPVIRHYKVMSVGQnyTIELEKPvTCPNLFSVINYFVKE 84
GDPD cd08556
Glycerophosphodiester phosphodiesterase domain as found in prokaryota and eukaryota, and ...
347-403 3.04e-03

Glycerophosphodiester phosphodiesterase domain as found in prokaryota and eukaryota, and similar proteins; The typical glycerophosphodiester phosphodiesterase domain (GDPD) consists of a TIM barrel and a small insertion domain named the GDPD-insertion (GDPD-I) domain, which is specific for GDPD proteins. This family corresponds to both typical GDPD domain and GDPD-like domain which lacks the GDPD-I region. Members in this family mainly consist of a large family of prokaryotic and eukaryotic glycerophosphodiester phosphodiesterases (GP-GDEs, EC 3.1.4.46), and a number of uncharacterized homologs. Sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria are also included in this family. GDPD plays an essential role in glycerol metabolism and catalyzes the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols are major sources of carbon and phosphate. Its catalytic mechanism is based on the metal ion-dependent acid-base reaction, which is similar to that of phosphoinositide-specific phospholipases C (PI-PLCs, EC 3.1.4.11). Both, GDPD related proteins and PI-PLCs, belong to the superfamily of PI-PLC-like phosphodiesterases.


Pssm-ID: 176499 [Multi-domain]  Cd Length: 189  Bit Score: 40.32  E-value: 3.04e-03
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gi 530418161  347 ESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYH-GHTLttkikfSDVLHTIKEHAFV 403
Cdd:cd08556    13 ENTLAAFRKALEAGADGVELDVQLTKDGVLVVIHdIPTL------EEVLELVKGGVGL 64
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
557-645 3.29e-03

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 38.46  E-value: 3.29e-03
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gi 530418161  557 AGRDGRHIAERLLTEycietgAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQDAgtpkFFLTDNLVFDSLYDLI 636
Cdd:cd10405     9 AGPMERAGAESILAN------RSDGTYLVRQRVKDAAEFAISIKYNVEVKHIKIMTAEGL----YRITEKKAFRGLTELV 78

                  ....*....
gi 530418161  637 THYQQVPLR 645
Cdd:cd10405    79 EFYQQNSLK 87
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
796-846 3.61e-03

Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this family contain a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains. They include the Rho guanine nucleotide exchange factors ARHGEF9, ASEF (also called ARHGEF4), ASEF2, and similar proteins. GEFs activate small GTPases by exchanging bound GDP for free GTP. ARHGEF9 specifically activates Cdc42, while both ASEF and ASEF2 can activate Rac1 and Cdc42. ARHGEF9 is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. ASEF plays a role in angiogenesis and cell migration. ASEF2 is important in cell migration and adhesion dynamics. ASEF exists in an autoinhibited form and is activated upon binding of the tumor suppressor APC (adenomatous polyposis coli), leading to the activation of Rac1 or Cdc42. In its autoinhibited form, the SH3 domain of ASEF forms an extensive interface with the DH and PH domains, blocking the Rac binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212762  Cd Length: 53  Bit Score: 36.98  E-value: 3.61e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYV 846
Cdd:cd11828     2 AEALWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRDEEG-WFPASFV 51
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
550-641 3.92e-03

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 38.19  E-value: 3.92e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietGAPDGSFLVRESETFVGDYTLSFWRNGKVQHCRIHSRQD--------AGTPKF 621
Cdd:cd10343     5 WYHGNIT-----RSKAEELLSK-----AGKDGSFLVRDSESVSGAYALCVLYQNCVHTYRILPNAEdklsvqasEGVPVR 74
                          90       100
                  ....*....|....*....|
gi 530418161  622 FltdnlvFDSLYDLITHYQQ 641
Cdd:cd10343    75 F------FTTLPELIEFYQK 88
SH3_Shank cd11832
Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank ...
795-843 4.16e-03

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212766  Cd Length: 50  Bit Score: 36.65  E-value: 4.16e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  795 AVKAlfdYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPS 843
Cdd:cd11832     4 AVKS---YSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTG-WFPS 48
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
491-570 4.71e-03

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 38.08  E-value: 4.71e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  491 KNGILYLEDPVNHEWYPHYFVLTSSKI-YYSEETSSDQGNEDEE-EPKEVSSSTELHSNEKwfHGKLGAGRDGRHIAERL 568
Cdd:cd13275     1 KKGWLMKQGSRQGEWSKHWFVLRGAALkYYRDPSAEEAGELDGViDLSSCTEVTELPVSRN--YGFQVKTWDGKVYVLSA 78

                  ..
gi 530418161  569 LT 570
Cdd:cd13275    79 MT 80
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
550-659 4.71e-03

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198214  Cd Length: 103  Bit Score: 37.95  E-value: 4.71e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  550 WFHGKLGagrdgRHIAERLLTEycietgAPDGSFLVRESETFVGdYTLSFWRNGKVQHCRIHSRQDAGTpkFFLTDNLVF 629
Cdd:cd10351     9 WFHGIIS-----REEAEALLMN------ATEGSFLVRVSEKIWG-YTLSYRLQSGFKHFLVDASGDFYS--FLGVDPNRH 74
                          90       100       110
                  ....*....|....*....|....*....|
gi 530418161  630 DSLYDLITHYQQVPLRCNEFEMrLSEPVPQ 659
Cdd:cd10351    75 ATLTDLIDFHKEEIITTSGGEL-LQEPCGQ 103
SH2_ShkD_ShkE cd10357
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE) ...
666-720 5.05e-03

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkD and shkE. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198220  Cd Length: 87  Bit Score: 37.49  E-value: 5.05e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 530418161  666 KEWYHASLTRAQAEHMLMRVPrDGAFLVR-KRNEPNS--YAISFRAEGKIKHCRVQQE 720
Cdd:cd10357    10 KSWFHGDISRDEAEKRLRGRP-EGTFLIRlSSTDPKKtpFTISKKKKSKPVHKRISRI 66
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
156-306 5.23e-03

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.


Pssm-ID: 320032 [Multi-domain]  Cd Length: 140  Bit Score: 38.75  E-value: 5.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  156 WLRKQFYSVDRNREDRISAKDLKNMLSQVNYRVPNM---RFLRERLTDleqRSGDITYGQFAQLYRSLMysaqktmdlpf 232
Cdd:cd16202     1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDyakKLFQEADTS---GEDVLDEEEFVQFYNRLT----------- 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  233 leastlragERPELCRV-----------SLPEFQQFLLDYQGELwAVDRLQVQEFMLSF-LRDPLREIEepYFFLDEFVT 300
Cdd:cd16202    67 ---------KRPEIEELfkkysgddealTVEELRRFLQEEQKVK-DVTLEWAEQLIETYePSEDLKAQG--LMSLDGFTL 134

                  ....*.
gi 530418161  301 FLFSKE 306
Cdd:cd16202   135 FLLSPD 140
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
796-846 5.66e-03

Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes to the plasma membrane and is required for dorsal ruffle formation. It binds phosphoinositides (PIs) with high affinity through its N-terminal SYLF domain (also called DUF500). In addition, SH3YL1 contains a C-terminal SH3 domain which has been reported to bind to N-WASP, dynamin 2, and SHIP2 (a PI 5-phosphatase). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212775  Cd Length: 54  Bit Score: 36.22  E-value: 5.66e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEK--QEGGWWRGDYGGKKQLwFPSNYV 846
Cdd:cd11841     2 VTALYSFEGQQPCDLSFQAGDRITVLTRtdSQFDWWEGRLRGRVGI-FPANYV 53
SH3_Irsp53_BAIAP2L cd11779
Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific ...
796-847 5.70e-03

Src Homology 3 domain of Insulin Receptor tyrosine kinase Substrate p53, Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2 (BAIAP2)-Like proteins, and similar proteins; Proteins in this family include IRSp53, BAIAP2L1, BAIAP2L2, and similar proteins. They all contain an Inverse-Bin/Amphiphysin/Rvs (I-BAR) or IMD domain in addition to the SH3 domain. IRSp53, also known as BAIAP2, is a scaffolding protein that takes part in many signaling pathways including Cdc42-induced filopodia formation, Rac-mediated lamellipodia extension, and spine morphogenesis. IRSp53 exists as multiple splicing variants that differ mainly at the C-termini. BAIAP2L1, also called IRTKS (Insulin Receptor Tyrosine Kinase Substrate), serves as a substrate for the insulin receptor and binds the small GTPase Rac. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. IRSp53 and IRTKS also mediate the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites. BAIAP2L2 co-localizes with clathrin plaques but its function has not been determined. The SH3 domains of IRSp53 and IRTKS have been shown to bind the proline-rich C-terminus of EspFu. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212713 [Multi-domain]  Cd Length: 57  Bit Score: 36.53  E-value: 5.70e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNV-EKQEGGWWRG-DYGGKKQLWFPSNYVE 847
Cdd:cd11779     3 VKALYPHAAGGETQLSFEEGDVITLLgPEPRDGWHYGeNERSGRRGWFPIAYTE 56
SH3_SH3RF3_3 cd11925
Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ...
798-846 5.82e-03

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212858  Cd Length: 57  Bit Score: 36.51  E-value: 5.82e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  798 ALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGD--YGGKKQLwFPSNYV 846
Cdd:cd11925     5 ALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTslRTGVSGV-FPGNYV 54
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
796-846 5.95e-03

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212898 [Multi-domain]  Cd Length: 57  Bit Score: 36.52  E-value: 5.95e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 530418161  796 VKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGG--KKQLWFPSNYV 846
Cdd:cd11965     2 VKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGqpERKGVFPVSFV 54
SH3_Sorbs2_3 cd11917
Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), ...
797-849 6.79e-03

Third (or C-terminal) Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called Arg-binding protein 2 (ArgBP2); Sorbs2 or ArgBP2 is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. It regulates actin-dependent processes including cell adhesion, morphology, and migration. It is expressed in many tissues and is abundant in the heart. Like vinexin, it is found in focal adhesion where it interacts with vinculin and afadin. It also localizes in epithelial cell stress fibers and in cardiac muscle cell Z-discs. Sorbs2 has been implicated to play roles in the signaling of c-Arg, Akt, and Pyk2. Other interaction partners of Sorbs2 include c-Abl, flotillin, spectrin, dynamin 1/2, synaptojanin, PTP-PEST, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212850 [Multi-domain]  Cd Length: 61  Bit Score: 36.12  E-value: 6.79e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQL-WFPSNYVEEM 849
Cdd:cd11917     8 QALYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSRRTKFFgTFPGNYVKRL 61
SH3_p47phox_1 cd12021
First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called ...
797-847 7.42e-03

First or N-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the first SH3 domain (or N-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212954  Cd Length: 53  Bit Score: 36.09  E-value: 7.42e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  797 KALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVE 847
Cdd:cd12021     3 RAIADYEKSSKSEMALKTGDVVEVVEKSENGWWFCQLKAKRG-WVPASYLE 52
SH3_p47phox_2 cd12022
Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also ...
801-848 8.88e-03

Second or C-terminal Src homology 3 domain of the p47phox subunit of NADPH oxidase, also called Neutrophil Cytosolic Factor 1; p47phox, or NCF1, is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal Phox homology (PX) domain, tandem SH3 domains (N-SH3 and C-SH3), a polybasic/autoinhibitory region, and a C-terminal proline-rich region (PRR). This model characterizes the second SH3 domain (or C-SH3) of p47phox. In its inactive state, the tandem SH3 domains interact intramolecularly with the autoinhibitory region; upon activation, the tandem SH3 domains are exposed through a conformational change, resulting in their binding to the PRR of p22phox and the activation of NADPH oxidase. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212955 [Multi-domain]  Cd Length: 53  Bit Score: 35.58  E-value: 8.88e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 530418161  801 DYKAQREDELTFIKSAIIQNVEKQEGGWW---RGDYGGkkqlWFPSNYVEE 848
Cdd:cd12022     7 AYTAVEEDELTLLEGEAIEVIHKLLDGWWvvrKGEVTG----YFPSMYLQK 53
SH2_RIN1 cd10393
Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a ...
668-741 9.32e-03

Src homology 2 (SH2) domain found in Ras and Rab interactor 1 (RIN1)-like proteins; RIN1, a member of the RIN (AKA Ras interaction/interference) family, have multifunctional domains including SH2 and proline-rich (PR) domains in the N-terminal region, and RIN-family homology (RH), VPS9 and Ras-association (RA) domains in the C-terminal region. RIN proteins function as Rab5-GEFs. Previous studies showed that RIN1 interacts with EGF receptors via its SH2 domain and regulates trafficking and degradation of EGF receptors via its interaction with STAM, indicating a vital role for RIN1 in regulating endosomal trafficking of receptor tyrosine kinases (RTKs). RIN1 was first identified as a Ras-binding protein that suppresses the activated RAS2 allele in S. cerevisiae. RIN1 binds to the activated Ras through its carboxyl-terminal domain and this Ras-binding domain also binds to 14-3-3 proteins as Raf-1 does. The SH2 domain of RIN1 are thought to interact with the phosphotyrosine-containing proteins, but the physiological partners for this domain are unknown. The proline-rich domain in RIN1 is similar to the consensus SH3 binding regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198256  Cd Length: 101  Bit Score: 37.14  E-value: 9.32e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418161  668 WYHASLTRAQAEHMLMRVPrDGAFLVRKRNEPNSYAISFR---AEGK--IKHCRVQQEGQTVMLGNSE--FDSLVDLISY 740
Cdd:cd10393    12 WLQLRANAAAALHVLRTEP-PGTFLVRKSNTRQCQALCVRlpeASGPsfVSSHYIQESPGGVSLEGSEltFPDLVQLICA 90

                  .
gi 530418161  741 Y 741
Cdd:cd10393    91 Y 91
SH3_Eve1_2 cd11815
Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
799-847 9.42e-03

Second Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 domain-containing protein 19 (SH3D19) or EEN-binding protein (EBP), exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. It is abundantly expressed in skeletal muscle and heart, and may be involved in regulating the activity of ADAMs (A disintegrin and metalloproteases). Eve-1 interacts with EEN, an endophilin involved in endocytosis and may be the target of the MLL-EEN fusion protein that is implicated in leukemogenesis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212749 [Multi-domain]  Cd Length: 52  Bit Score: 35.62  E-value: 9.42e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530418161  799 LFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLwFPSNYVE 847
Cdd:cd11815     5 LHDFPAEHSDDLSLNSGEIVYLLEKIDTEWYRGKCKNTTGI-FPANHVK 52
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
1170-1241 9.78e-03

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 37.24  E-value: 9.78e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530418161 1170 TVDNGLNPVWpAKPFHFQISNPEFAFLRFVVYEEDMFSDQNfLAQATFPVKGLKTGYR---AVPLKNNYSEDLEL 1241
Cdd:cd04036    41 TIKNSINPVW-NETFEFRIQSQVKNVLELTVMDEDYVMDDH-LGTVLFDVSKLKLGEKvrvTFSLNPQGKEELEV 113
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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