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Conserved domains on  [gi|166064038|ref|NP_001106985.1|]
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rho guanine nucleotide exchange factor 7 isoform a [Homo sapiens]

Protein Classification

PH_Cool_Pix and RhoGEF67_u2 domain-containing protein (domain architecture ID 10879110)

protein containing domains RhoGEF, PH_Cool_Pix, RhoGEF67_u2, and betaPIX_CC

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_Cool_Pix cd01225
Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There ...
302-400 6.12e-58

Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6/90Cool-2) and beta Pix (GEF7/p85Cool-1). betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity. 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: 269932  Cd Length: 100  Bit Score: 191.37  E-value: 6.12e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038 302 VTYMSQVLIQCAGSEEKNERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSENHRNAFEISGSMIERILVS 381
Cdd:cd01225    1 VIHMSQVAVQNTGCQEKKERYFLLFPHVLLMLSASPRMSGFIYEGKLPLTGISVNRLEDTEGIKNAFEISGPLIERIVVI 80
                         90
                 ....*....|....*....
gi 166064038 382 CNNQQDLQEWVEHLQKQTK 400
Cdd:cd01225   81 CNSQQDQQEWLEHLQQQTK 99
RhoGEF67_u2 pfam16614
Unstructured region two on RhoGEF 6 and 7; RhoGEF67_u2 is a region of natively unstructured ...
456-554 6.68e-57

Unstructured region two on RhoGEF 6 and 7; RhoGEF67_u2 is a region of natively unstructured residues on Rho guanine nucleotide exchange factor 6 and 7 proteins. The function is not known. It lies after the PH domain and before the C-terminal coiled-coil.


:

Pssm-ID: 293220  Cd Length: 108  Bit Score: 189.06  E-value: 6.68e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  456 TTINWGPLEPPKTPKPWSLSCLRPAPPLRPSAALCYKE-------DLSKSPKTMKKLLPKRKPERKPSDEEFASRKSTAA 528
Cdd:pfam16614   3 TGQPRGPLEPPKIPKPWSLSCLRPAPPLRPSAALGYKErmsyilkDSSKSPKTMKKFLPKRKTERKPSDEEFAIRKSTVA 82
                          90       100
                  ....*....|....*....|....*.
gi 166064038  529 LEEDAQILKVIEAYCTSAKTRQTLNS 554
Cdd:pfam16614  83 LEEDAQILKVIEAYCTGASFQQSLNS 108
betaPIX_CC pfam16523
betaPIX coiled coil; betaPIX_CC is the very C-terminal coiled-coil region of betaPIX or ...
557-643 1.64e-45

betaPIX coiled coil; betaPIX_CC is the very C-terminal coiled-coil region of betaPIX or p21-activated kinase interacting exchange factor proteins. The coiled-coil runs from residues 589-646 in UniProtKB:G31IU6, and the PDZ-binding site is the final eight residues immediately downstream. The coiled-coil trimerizes and thus exposes three potential PZD-binding surfaces, although only one of these is maximally used. One of the C-terminal ends of the coiled-coil forms an extensive beta-sheet interaction with the Shank PDZ, while the other two ends are not involved in ligand binding and form random coils. Thus the coiled-coil domain allows multimerization of betaPIX that is vital for its physiological functions. betaPIX and the Shank/ProSAP protein form a complex that acts as a protein scaffold for integrating signalling pathways and regulating postsynaptic structure.** Forced reload


:

Pssm-ID: 293131  Cd Length: 86  Bit Score: 156.36  E-value: 1.64e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  557 RKESAPQVLLPEEEKIIVEETKSNgQTVIEEKSLVDTVYALKDEVQELRQDNKKMKKSLEEEQRARKDLEKLVRKVLKNM 636
Cdd:pfam16523   1 RKYQAPQLLVPEEEKIIVEEMKGN-QTVLQEKSLVDTVYALKDQVQELKQENKKMKKTLEEEQKARRRLEKVVRKLLKSI 79

                  ....*..
gi 166064038  637 NDPAWDE 643
Cdd:pfam16523  80 NDDGWDE 86
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
94-271 1.00e-39

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 238091  Cd Length: 181  Bit Score: 143.59  E-value: 1.00e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  94 YNVVLQNILETENEYSKELQTVLSTYLRPLQTSEK-LSSANISYLMGNLEEICSFQQMLVQSLEECTKL-PEAQQRVGGC 171
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEwDKSGPRIGDV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038 172 FLNLMPQMKTlYLTYCANHPSAVNVLTEHSEELGEFME--TKGASSPGILVLTTGLSKPFMRLDKYPTLLKELERHMEDY 249
Cdd:cd00160   81 FLKLAPFFKI-YSEYCSNHPDALELLKKLKKFNKFFQEflEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159
                        170       180
                 ....*....|....*....|..
gi 166064038 250 HTDRQDIQKSMAAFKNLSAQCQ 271
Cdd:cd00160  160 HEDREDLKKALEAIKEVASQVN 181
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
10-63 1.11e-35

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  Cd Length: 54  Bit Score: 128.65  E-value: 1.11e-35
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:cd12061    1 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 54
PH pfam00169
PH domain; PH stands for pleckstrin homology.
320-400 3.02e-10

PH domain; PH stands for pleckstrin homology.


:

Pssm-ID: 278594 [Multi-domain]  Cd Length: 105  Bit Score: 57.95  E-value: 3.02e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  320 ERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKL--EDSENHRNAFEISGSMI---ERILVSCNNQQDLQEWVEH 394
Cdd:pfam00169  20 KRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVvaPDSPKRKFCFELRTGERdggRTYLLQAESEEERKEWIKA 99

                  ....*.
gi 166064038  395 LQKQTK 400
Cdd:pfam00169 100 IQSAIR 105
 
Name Accession Description Interval E-value
PH_Cool_Pix cd01225
Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There ...
302-400 6.12e-58

Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6/90Cool-2) and beta Pix (GEF7/p85Cool-1). betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity. 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: 269932  Cd Length: 100  Bit Score: 191.37  E-value: 6.12e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038 302 VTYMSQVLIQCAGSEEKNERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSENHRNAFEISGSMIERILVS 381
Cdd:cd01225    1 VIHMSQVAVQNTGCQEKKERYFLLFPHVLLMLSASPRMSGFIYEGKLPLTGISVNRLEDTEGIKNAFEISGPLIERIVVI 80
                         90
                 ....*....|....*....
gi 166064038 382 CNNQQDLQEWVEHLQKQTK 400
Cdd:cd01225   81 CNSQQDQQEWLEHLQQQTK 99
RhoGEF67_u2 pfam16614
Unstructured region two on RhoGEF 6 and 7; RhoGEF67_u2 is a region of natively unstructured ...
456-554 6.68e-57

Unstructured region two on RhoGEF 6 and 7; RhoGEF67_u2 is a region of natively unstructured residues on Rho guanine nucleotide exchange factor 6 and 7 proteins. The function is not known. It lies after the PH domain and before the C-terminal coiled-coil.


Pssm-ID: 293220  Cd Length: 108  Bit Score: 189.06  E-value: 6.68e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  456 TTINWGPLEPPKTPKPWSLSCLRPAPPLRPSAALCYKE-------DLSKSPKTMKKLLPKRKPERKPSDEEFASRKSTAA 528
Cdd:pfam16614   3 TGQPRGPLEPPKIPKPWSLSCLRPAPPLRPSAALGYKErmsyilkDSSKSPKTMKKFLPKRKTERKPSDEEFAIRKSTVA 82
                          90       100
                  ....*....|....*....|....*.
gi 166064038  529 LEEDAQILKVIEAYCTSAKTRQTLNS 554
Cdd:pfam16614  83 LEEDAQILKVIEAYCTGASFQQSLNS 108
betaPIX_CC pfam16523
betaPIX coiled coil; betaPIX_CC is the very C-terminal coiled-coil region of betaPIX or ...
557-643 1.64e-45

betaPIX coiled coil; betaPIX_CC is the very C-terminal coiled-coil region of betaPIX or p21-activated kinase interacting exchange factor proteins. The coiled-coil runs from residues 589-646 in UniProtKB:G31IU6, and the PDZ-binding site is the final eight residues immediately downstream. The coiled-coil trimerizes and thus exposes three potential PZD-binding surfaces, although only one of these is maximally used. One of the C-terminal ends of the coiled-coil forms an extensive beta-sheet interaction with the Shank PDZ, while the other two ends are not involved in ligand binding and form random coils. Thus the coiled-coil domain allows multimerization of betaPIX that is vital for its physiological functions. betaPIX and the Shank/ProSAP protein form a complex that acts as a protein scaffold for integrating signalling pathways and regulating postsynaptic structure.** Forced reload


Pssm-ID: 293131  Cd Length: 86  Bit Score: 156.36  E-value: 1.64e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  557 RKESAPQVLLPEEEKIIVEETKSNgQTVIEEKSLVDTVYALKDEVQELRQDNKKMKKSLEEEQRARKDLEKLVRKVLKNM 636
Cdd:pfam16523   1 RKYQAPQLLVPEEEKIIVEEMKGN-QTVLQEKSLVDTVYALKDQVQELKQENKKMKKTLEEEQKARRRLEKVVRKLLKSI 79

                  ....*..
gi 166064038  637 NDPAWDE 643
Cdd:pfam16523  80 NDDGWDE 86
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
94-271 1.00e-39

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091  Cd Length: 181  Bit Score: 143.59  E-value: 1.00e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  94 YNVVLQNILETENEYSKELQTVLSTYLRPLQTSEK-LSSANISYLMGNLEEICSFQQMLVQSLEECTKL-PEAQQRVGGC 171
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEwDKSGPRIGDV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038 172 FLNLMPQMKTlYLTYCANHPSAVNVLTEHSEELGEFME--TKGASSPGILVLTTGLSKPFMRLDKYPTLLKELERHMEDY 249
Cdd:cd00160   81 FLKLAPFFKI-YSEYCSNHPDALELLKKLKKFNKFFQEflEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159
                        170       180
                 ....*....|....*....|..
gi 166064038 250 HTDRQDIQKSMAAFKNLSAQCQ 271
Cdd:cd00160  160 HEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
97-272 2.21e-37

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 279015  Cd Length: 180  Bit Score: 137.35  E-value: 2.21e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038   97 VLQNILETENEYSKELQTVLSTYLRPLQTSEK-LSSANISYLMGNLEEICSFQQMLVQSLEECTKLPEAQQRVGGCFLNL 175
Cdd:pfam00621   1 VIQELLQTERSYVRDLEILIEVFLKPLREAPPiLSEEEIKTIFSNIEEILELHQEFLEELEERLKEWSDIQRIGDIFLKF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  176 MPQMKtLYLTYCANHPSAVNVLTEHSEE---LGEFMETKGASS-PGILVLTTGLSKPFMRLDKYPTLLKELERHMEDYHT 251
Cdd:pfam00621  81 EPFFK-VYSTYCSNYPKALELLKKLKKKnpkFAKFLKECEANPlCRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 159
                         170       180
                  ....*....|....*....|.
gi 166064038  252 DRQDIQKSMAAFKNLSAQCQE 272
Cdd:pfam00621 160 DYEDLKKALEAIKEVAKQINE 180
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
97-272 5.15e-37

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619  Cd Length: 180  Bit Score: 136.28  E-value: 5.15e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038    97 VLQNILETENEYSKELQTVLSTYLRPLQTSEKLSSAN-ISYLMGNLEEICSFQQMLVQSLEECTKLPE-AQQRVGGCFLN 174
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNeLETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGDVFLK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038   175 LMPqMKTLYLTYCANHPSAVNVLTE--HSEELGEFMETKGASSPGI-LVLTTGLSKPFMRLDKYPTLLKELERHMEDYHT 251
Cdd:smart00325  81 LEE-FFKIYSEYCSNHPDALELLKKlkKNPRFQKFLKEIESSPQCRrLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159
                          170       180
                   ....*....|....*....|.
gi 166064038   252 DRQDIQKSMAAFKNLSAQCQE 272
Cdd:smart00325 160 DREDLKKALKAIKELANQVNE 180
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
10-63 1.11e-35

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  Cd Length: 54  Bit Score: 128.65  E-value: 1.11e-35
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:cd12061    1 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 54
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
11-61 1.71e-21

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  Cd Length: 56  Bit Score: 89.13  E-value: 1.71e-21
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 166064038    11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLN-GRTGWFPSNYVR 61
Cdd:smart00326   5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
10-63 2.70e-17

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


Pssm-ID: 284963  Cd Length: 54  Bit Score: 77.13  E-value: 2.70e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 166064038   10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:pfam07653   1 YGRAIFDYVGTDPTELSLKKGDVIKVIDKDSDGWWEGENGGRKGLVPSSAVEEI 54
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
314-400 7.23e-11

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: 59.87  E-value: 7.23e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038   314 GSEEKNERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSEN--HRNAFEISGSMIERILVSCNNQQDLQEW 391
Cdd:smart00233  14 GKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSskKPHCFEIKTSDRKTLLLQAESEEEREKW 93

                   ....*....
gi 166064038   392 VEHLQKQTK 400
Cdd:smart00233  94 VEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
320-400 3.02e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 278594 [Multi-domain]  Cd Length: 105  Bit Score: 57.95  E-value: 3.02e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  320 ERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKL--EDSENHRNAFEISGSMI---ERILVSCNNQQDLQEWVEH 394
Cdd:pfam00169  20 KRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVvaPDSPKRKFCFELRTGERdggRTYLLQAESEEERKEWIKA 99

                  ....*.
gi 166064038  395 LQKQTK 400
Cdd:pfam00169 100 IQSAIR 105
PHA03247 PHA03247
large tegument protein UL36; Provisional
407-516 1.35e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 47.24  E-value: 1.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  407 PTIKPHSVPSHTLPSHPVTPSSKHADSKPAPLTPAYHTLPHPSHHGT-PHTTINWGPLEPPKTPKPWSLSclRPAPPLRP 485
Cdd:PHA03247 2771 PPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAAlPPAASPAGPLPPPTSAQPTAPP--PPPGPPPP 2848
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 166064038  486 SAALCYK----EDLSKSPktmkkllPKRKPERKPS 516
Cdd:PHA03247 2849 SLPLGGSvapgGDVRRRP-------PSRSPAAKPA 2876
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
104-267 4.71e-05

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 45.27  E-value: 4.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  104 TENEYSKELQTVLSTYLRPLQTSEKLSSAN----ISYLMGNLEEICSFQQMLVQSLEECTKLPEAQQRVGGCFLNLMPQM 179
Cdd:COG5422   495 TERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANINEIYAVNSKLLKALTNRQCLSPIVNGIADIFLDYVPKF 574
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  180 KTlYLTYCANHPSAVNVLTEHSEELGEFM----ETKGASSPGILVLTTGLSKPFMRLDKYPTLLKELERHMEDYHTDRQD 255
Cdd:COG5422   575 EP-FIKYGASQPYAKYEFEREKSVNPNFArfdhEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTED 653
                         170
                  ....*....|..
gi 166064038  256 IQKSMAAFKNLS 267
Cdd:COG5422   654 IPKVIDMLREFL 665
GGN pfam15685
Gametogenetin; GGN is a family of proteins largely found in mammals. It reacts with POG in the ...
407-529 1.27e-04

Gametogenetin; GGN is a family of proteins largely found in mammals. It reacts with POG in the maturation of sperm and is expressed virtually only in the testis. It is found to be associated with the intracellular membrane, binds with GGNBP1 and may be involved in vesicular trafficking.


Pssm-ID: 292313 [Multi-domain]  Cd Length: 653  Bit Score: 43.56  E-value: 1.27e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  407 PTIKPHSVP-SHTLPShPVTPSSKHADS-KPAPLTPAYHTLPHPSH----HGTPHTTINwGPLEPPKTPKPWSLScLRPA 480
Cdd:pfam15685  67 PQASPSPLPlTLELPS-PVTPPPEEAAAvSTPPPPPVGTLLPGPSKwrkpTGTAVPRIR-GLLEASHRGQGDPPS-LRPP 143
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  481 PPLRPSaALCYKEDLSKSPKTM--KKLLPKRKPERKPSDEEFASRKSTAAL 529
Cdd:pfam15685 144 LPPLPR-QLTEKDPVPRAPVQPppTPLEPRKPPPPPPSDWQPASRRITPAL 193
 
Name Accession Description Interval E-value
PH_Cool_Pix cd01225
Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There ...
302-400 6.12e-58

Cloned out of library/PAK-interactive exchange factor pleckstrin homology (PH) domain; There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6/90Cool-2) and beta Pix (GEF7/p85Cool-1). betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity. 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: 269932  Cd Length: 100  Bit Score: 191.37  E-value: 6.12e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038 302 VTYMSQVLIQCAGSEEKNERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSENHRNAFEISGSMIERILVS 381
Cdd:cd01225    1 VIHMSQVAVQNTGCQEKKERYFLLFPHVLLMLSASPRMSGFIYEGKLPLTGISVNRLEDTEGIKNAFEISGPLIERIVVI 80
                         90
                 ....*....|....*....
gi 166064038 382 CNNQQDLQEWVEHLQKQTK 400
Cdd:cd01225   81 CNSQQDQQEWLEHLQQQTK 99
RhoGEF67_u2 pfam16614
Unstructured region two on RhoGEF 6 and 7; RhoGEF67_u2 is a region of natively unstructured ...
456-554 6.68e-57

Unstructured region two on RhoGEF 6 and 7; RhoGEF67_u2 is a region of natively unstructured residues on Rho guanine nucleotide exchange factor 6 and 7 proteins. The function is not known. It lies after the PH domain and before the C-terminal coiled-coil.


Pssm-ID: 293220  Cd Length: 108  Bit Score: 189.06  E-value: 6.68e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  456 TTINWGPLEPPKTPKPWSLSCLRPAPPLRPSAALCYKE-------DLSKSPKTMKKLLPKRKPERKPSDEEFASRKSTAA 528
Cdd:pfam16614   3 TGQPRGPLEPPKIPKPWSLSCLRPAPPLRPSAALGYKErmsyilkDSSKSPKTMKKFLPKRKTERKPSDEEFAIRKSTVA 82
                          90       100
                  ....*....|....*....|....*.
gi 166064038  529 LEEDAQILKVIEAYCTSAKTRQTLNS 554
Cdd:pfam16614  83 LEEDAQILKVIEAYCTGASFQQSLNS 108
betaPIX_CC pfam16523
betaPIX coiled coil; betaPIX_CC is the very C-terminal coiled-coil region of betaPIX or ...
557-643 1.64e-45

betaPIX coiled coil; betaPIX_CC is the very C-terminal coiled-coil region of betaPIX or p21-activated kinase interacting exchange factor proteins. The coiled-coil runs from residues 589-646 in UniProtKB:G31IU6, and the PDZ-binding site is the final eight residues immediately downstream. The coiled-coil trimerizes and thus exposes three potential PZD-binding surfaces, although only one of these is maximally used. One of the C-terminal ends of the coiled-coil forms an extensive beta-sheet interaction with the Shank PDZ, while the other two ends are not involved in ligand binding and form random coils. Thus the coiled-coil domain allows multimerization of betaPIX that is vital for its physiological functions. betaPIX and the Shank/ProSAP protein form a complex that acts as a protein scaffold for integrating signalling pathways and regulating postsynaptic structure.** Forced reload


Pssm-ID: 293131  Cd Length: 86  Bit Score: 156.36  E-value: 1.64e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  557 RKESAPQVLLPEEEKIIVEETKSNgQTVIEEKSLVDTVYALKDEVQELRQDNKKMKKSLEEEQRARKDLEKLVRKVLKNM 636
Cdd:pfam16523   1 RKYQAPQLLVPEEEKIIVEEMKGN-QTVLQEKSLVDTVYALKDQVQELKQENKKMKKTLEEEQKARRRLEKVVRKLLKSI 79

                  ....*..
gi 166064038  637 NDPAWDE 643
Cdd:pfam16523  80 NDDGWDE 86
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
94-271 1.00e-39

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091  Cd Length: 181  Bit Score: 143.59  E-value: 1.00e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  94 YNVVLQNILETENEYSKELQTVLSTYLRPLQTSEK-LSSANISYLMGNLEEICSFQQMLVQSLEECTKL-PEAQQRVGGC 171
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEwDKSGPRIGDV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038 172 FLNLMPQMKTlYLTYCANHPSAVNVLTEHSEELGEFME--TKGASSPGILVLTTGLSKPFMRLDKYPTLLKELERHMEDY 249
Cdd:cd00160   81 FLKLAPFFKI-YSEYCSNHPDALELLKKLKKFNKFFQEflEKAESECGRLKLESLLLKPVQRLTKYPLLLKELLKHTPDG 159
                        170       180
                 ....*....|....*....|..
gi 166064038 250 HTDRQDIQKSMAAFKNLSAQCQ 271
Cdd:cd00160  160 HEDREDLKKALEAIKEVASQVN 181
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
97-272 2.21e-37

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 279015  Cd Length: 180  Bit Score: 137.35  E-value: 2.21e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038   97 VLQNILETENEYSKELQTVLSTYLRPLQTSEK-LSSANISYLMGNLEEICSFQQMLVQSLEECTKLPEAQQRVGGCFLNL 175
Cdd:pfam00621   1 VIQELLQTERSYVRDLEILIEVFLKPLREAPPiLSEEEIKTIFSNIEEILELHQEFLEELEERLKEWSDIQRIGDIFLKF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  176 MPQMKtLYLTYCANHPSAVNVLTEHSEE---LGEFMETKGASS-PGILVLTTGLSKPFMRLDKYPTLLKELERHMEDYHT 251
Cdd:pfam00621  81 EPFFK-VYSTYCSNYPKALELLKKLKKKnpkFAKFLKECEANPlCRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 159
                         170       180
                  ....*....|....*....|.
gi 166064038  252 DRQDIQKSMAAFKNLSAQCQE 272
Cdd:pfam00621 160 DYEDLKKALEAIKEVAKQINE 180
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
97-272 5.15e-37

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619  Cd Length: 180  Bit Score: 136.28  E-value: 5.15e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038    97 VLQNILETENEYSKELQTVLSTYLRPLQTSEKLSSAN-ISYLMGNLEEICSFQQMLVQSLEECTKLPE-AQQRVGGCFLN 174
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNeLETLFGNIEEIYEFHRDFLDELEERIEEWDdSVERIGDVFLK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038   175 LMPqMKTLYLTYCANHPSAVNVLTE--HSEELGEFMETKGASSPGI-LVLTTGLSKPFMRLDKYPTLLKELERHMEDYHT 251
Cdd:smart00325  81 LEE-FFKIYSEYCSNHPDALELLKKlkKNPRFQKFLKEIESSPQCRrLTLESLLLKPVQRLTKYPLLLKELLKHTPEDHE 159
                          170       180
                   ....*....|....*....|.
gi 166064038   252 DRQDIQKSMAAFKNLSAQCQE 272
Cdd:smart00325 160 DREDLKKALKAIKELANQVNE 180
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
10-63 1.11e-35

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  Cd Length: 54  Bit Score: 128.65  E-value: 1.11e-35
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:cd12061    1 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 54
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
8-65 1.04e-33

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: 123.19  E-value: 1.04e-33
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 166064038   8 QLVVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREVKA 65
Cdd:cd12060    1 QLVVKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTGWFPSNYVREIKS 58
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
10-62 3.48e-33

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  Cd Length: 53  Bit Score: 121.65  E-value: 3.48e-33
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11877    1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVKE 53
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
11-61 1.71e-21

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  Cd Length: 56  Bit Score: 89.13  E-value: 1.71e-21
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 166064038    11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLN-GRTGWFPSNYVR 61
Cdd:smart00326   5 VRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGrGKEGLFPSNYVE 56
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
10-59 5.07e-19

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  Cd Length: 51  Bit Score: 81.74  E-value: 5.07e-19
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLN-GRTGWFPSNY 59
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNgGREGLFPANY 51
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
11-62 3.99e-18

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  Cd Length: 53  Bit Score: 79.38  E-value: 3.99e-18
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11840    2 VIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQTGLFPSNYVEP 53
PH_PLEKHN1 cd13323
Pleckstrin homology domain containing family N member 1Pleckstrin homology-like domain; Not ...
297-420 4.38e-18

Pleckstrin homology domain containing family N member 1Pleckstrin homology-like domain; Not much is known about PLEKHN1. It is found in a wide range of animals including humans, green anole, frog, and zebrafish. It contains a single PH 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: 270132  Cd Length: 121  Bit Score: 80.98  E-value: 4.38e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038 297 KTLGNVTYMSQVLIQCAGSEEKNERYLLLFPNVLLMLSASPrmSGFIYQGKLPTTGMTITkLEDSENHRNAFEISGSMIE 376
Cdd:cd13323    2 ESLGSITCVSKVKLQHLPFQEQHDRLLVLYPSSLIILSEES--DGLCFKGELPLNAIQVN-FEENEKKIRSFLIEGRLIN 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 166064038 377 RILVSCNNQQDLQEWVEHLqKQTKVTSVGNPTIKPHSVPSHTLP 420
Cdd:cd13323   79 TIRVSCLSYEDYQDWILCL-KTAQVRNGDSSLPGSSSFYGSTQP 121
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
10-62 7.13e-18

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: 78.46  E-value: 7.13e-18
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11766    1 PAVVKFNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVGWFPSNYVTE 53
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
10-63 2.70e-17

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


Pssm-ID: 284963  Cd Length: 54  Bit Score: 77.13  E-value: 2.70e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 166064038   10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:pfam07653   1 YGRAIFDYVGTDPTELSLKKGDVIKVIDKDSDGWWEGENGGRKGLVPSSAVEEI 54
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
11-62 1.34e-16

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: 75.00  E-value: 1.34e-16
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11873    2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRGMFPDNFVKV 53
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
11-60 1.56e-16

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  Cd Length: 52  Bit Score: 74.67  E-value: 1.56e-16
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11826    2 VVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNGVTGLFPGNYV 51
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
12-62 6.94e-16

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  Cd Length: 53  Bit Score: 73.14  E-value: 6.94e-16
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11874    3 KVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
11-60 8.30e-16

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  Cd Length: 53  Bit Score: 72.66  E-value: 8.30e-16
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11805    2 VQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRGRVGIFPANYV 51
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
12-60 2.28e-15

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  Cd Length: 55  Bit Score: 71.73  E-value: 2.28e-15
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTR--VEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd12142    3 RVLFDYNPVAPDELALKKGDVIEVISkeTEDEGWWEGELNGRRGFFPDNFV 53
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
12-62 4.54e-15

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  Cd Length: 53  Bit Score: 70.83  E-value: 4.54e-15
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVEE 53
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
14-62 9.54e-15

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  Cd Length: 53  Bit Score: 69.92  E-value: 9.54e-15
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  14 KFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd12052    5 EFDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRGLFPDNFVRE 53
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
10-62 1.57e-14

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  Cd Length: 53  Bit Score: 69.25  E-value: 1.57e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11772    1 VFRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVEE 53
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
12-57 1.78e-14

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


Pssm-ID: 278447  Cd Length: 47  Bit Score: 68.75  E-value: 1.78e-14
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 166064038   12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGR-TGWFPS 57
Cdd:pfam00018   1 VALYDYTAREPDELSFKKGDVIIVLEKSDDGWWKGRLKGGgEGLIPS 47
SH3_9 pfam14604
Variant SH3 domain;
13-61 2.13e-14

Variant SH3 domain;


Pssm-ID: 291278  Cd Length: 50  Bit Score: 68.78  E-value: 2.13e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 166064038   13 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLN-GRTGWFPSNYVR 61
Cdd:pfam14604   1 ALYPYEPRDDDELSLRRGDVITVLEESEDGWLLGSNTtGRTGLVPANYVK 50
SH3_CIN85_2 cd12055
Second Src Homology 3 domain (SH3B) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
12-62 2.58e-14

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: 68.48  E-value: 2.58e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd12055    3 QVAFSYLPQNEDELELKVGDIIEVVGEVEEGWWEGVLNGKTGMFPSNFIKE 53
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
10-60 4.04e-14

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  Cd Length: 55  Bit Score: 68.15  E-value: 4.04e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTR--VEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSkdCEDKGWWKGELNGKRGVFPDNFV 53
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
13-62 5.78e-14

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  Cd Length: 54  Bit Score: 67.65  E-value: 5.78e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHV-TRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11830    4 ARYDFCARDMRELSLKEGDVVKIyNKKGQQGWWRGEINGRIGWFPSTYVEE 54
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
12-60 1.30e-13

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  Cd Length: 55  Bit Score: 66.61  E-value: 1.30e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG--GWWEGTLNGRTGWFPSNYV 60
Cdd:cd11836    3 RALYAFEARNPDEISFQPGDIIQVDESQVAepGWLAGELKGKTGWFPANYV 53
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
11-61 1.38e-13

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  Cd Length: 54  Bit Score: 66.54  E-value: 1.38e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11996    3 VIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGVTGLFPSNYVK 53
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
12-60 2.53e-13

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  Cd Length: 55  Bit Score: 65.74  E-value: 2.53e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVT-RVEEGgWWEGTLNGRTGWFPSNYV 60
Cdd:cd11803    4 RALYDFEPENEGELGFKEGDIITLTnQIDEN-WYEGMVNGQSGFFPVNYV 52
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
14-62 2.88e-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: 65.44  E-value: 2.88e-13
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  14 KFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11901    7 KFNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVGWFPSNYVTE 55
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
10-60 3.17e-13

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  Cd Length: 53  Bit Score: 65.44  E-value: 3.17e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11781    1 KARALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNGRVGIFPASYV 51
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
12-60 4.08e-13

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: 65.23  E-value: 4.08e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG--GWWEGTLNGRTGWFPSNYV 60
Cdd:cd12056    5 KALFHYEGTNEDELDFKEGEIILIISKDTGepGWWKGELNGKEGVFPDNFV 55
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
13-62 4.11e-13

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  Cd Length: 52  Bit Score: 65.13  E-value: 4.11e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRvEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11838    4 ALYPYESNEPGDLTFNAGDVILVTK-KDGEWWTGTIGDRTGIFPSNYVRP 52
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
17-61 5.14e-13

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: 65.05  E-value: 5.14e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  17 FQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGR-----TGWFPSNYVR 61
Cdd:cd11839    8 FTATAENQLSLAVGQLVLVRKKSPSGWWEGELQARgkkrqIGWFPANYVK 57
SH3_GRB2_C cd11949
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
11-61 6.08e-13

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  Cd Length: 53  Bit Score: 64.47  E-value: 6.08e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11949    2 VQALFDFDPQEDGELGFRRGDFIEVMDNSDPNWWKGACHGQTGMFPRNYVT 52
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
15-63 7.14e-13

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  Cd Length: 55  Bit Score: 64.60  E-value: 7.14e-13
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  15 FNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:cd12054    7 FEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNGKSGLFPSNFVKEL 55
SH3_Sdc25 cd11883
Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is ...
10-59 9.93e-13

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: 63.84  E-value: 9.93e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRT-----GWFPSNY 59
Cdd:cd11883    1 VVVALYDFTPKSKNQLSFKAGDIIYVLNKDPSGWWDGVIISSSgkvkrGWFPSNY 55
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
11-61 1.42e-12

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  Cd Length: 54  Bit Score: 63.47  E-value: 1.42e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIH-VTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11882    2 ARALYACKAEDESELSFEPGQIITnVQPSDEPGWLEGTLNGRTGLIPENYVE 53
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
11-62 1.50e-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: 63.57  E-value: 1.50e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEG----GWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11762    2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNgvddGWWEGEFNGRVGVFPSLVVEE 57
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
11-62 1.71e-12

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  Cd Length: 54  Bit Score: 63.12  E-value: 1.71e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGR-TGWFPSNYVRE 62
Cdd:cd11825    2 VKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKkQKWFPANYVEE 54
SH3_Shank cd11832
Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank ...
13-57 1.87e-12

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: 63.22  E-value: 1.87e-12
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPS 57
Cdd:cd11832    4 AVKSYSPQEEGEISLHKGDRVKVLSIGEGGFWEGSVRGRTGWFPS 48
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
10-62 2.41e-12

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  Cd Length: 54  Bit Score: 63.04  E-value: 2.41e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHV-TRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11976    1 TAKARYDFCARDRSELSLKEGDIIKIlNKKGQQGWWRGEIYGRVGWFPANYVEE 54
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
12-60 3.08e-12

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: 62.37  E-value: 3.08e-12
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11796    3 RVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNGRRGIFPEGFV 51
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
11-63 3.32e-12

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: 62.70  E-value: 3.32e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTG-WFPSNYVREV 63
Cdd:cd11970    6 VKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQlWFPSNYVEEI 59
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
11-62 3.61e-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  Cd Length: 53  Bit Score: 62.43  E-value: 3.61e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11827    2 CKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVEK 53
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
15-61 3.72e-12

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  Cd Length: 54  Bit Score: 62.28  E-value: 3.72e-12
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gi 166064038  15 FNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11995    7 YDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQVGLFPSNYVK 53
SH3_GRB2_like_N cd11804
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
12-60 4.52e-12

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  Cd Length: 52  Bit Score: 61.99  E-value: 4.52e-12
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gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG-GWWEGTLNGRTGWFPSNYV 60
Cdd:cd11804    3 VAKHDFKATAEDELSFKKGSILKVLNMEDDpNWYKAELDGKEGLIPKNYI 52
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
11-61 4.89e-12

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: 62.15  E-value: 4.89e-12
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11950    2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
13-62 5.06e-12

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  Cd Length: 56  Bit Score: 61.96  E-value: 5.06e-12
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHV-TRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11978    5 ARYDFCARDMRELSLLKGDVVKIyTKMSTNGWWRGEVNGRVGWFPSTYVEE 55
SH3_Shank1 cd11982
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 1; Shank1, also ...
17-60 7.83e-12

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  Cd Length: 52  Bit Score: 61.57  E-value: 7.83e-12
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gi 166064038  17 FQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11982    9 YQSQAEGEISLSKGEKIKVLSVGEGGFWEGQVKGRVGWFPSDCV 52
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
14-64 8.77e-12

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 [Multi-domain]  Cd Length: 56  Bit Score: 61.40  E-value: 8.77e-12
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gi 166064038  14 KFNFQQTNEDELSFSKGDVI-HVTRVEEGGWWEGTLNGRTGWFPSNYVREVK 64
Cdd:cd12053    5 EYDYDAVHEDELTIRVGEIIrNVKKLEEEGWLEGELNGRRGMFPDNFVKEIK 56
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
11-63 9.14e-12

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: 61.39  E-value: 9.14e-12
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTG-WFPSNYVREV 63
Cdd:cd11969    2 VKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQhYFPSNYVEDV 55
SH3_Intersectin1_3 cd11991
Third Src homology 3 domain (or SH3C) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
13-61 1.32e-11

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: 60.77  E-value: 1.32e-11
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRvEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11991    4 AMYTYESNEQGDLTFQQGDVILVTK-KDGDWWTGTVGDKTGVFPSNYVR 51
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
10-62 1.48e-11

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: 60.46  E-value: 1.48e-11
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gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGgWWEGTL-NGRTGWFPSNYVRE 62
Cdd:cd11837    1 TATALYPWRAKKENHLSFAKGDIITVLEQQEM-WWFGELeGGEEGWFPKSYVKE 53
SH3_Abi2 cd11972
Src homology 3 domain of Abl Interactor 2; Abi2 is highly expressed in the brain and eye. It ...
11-63 2.22e-11

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  Cd Length: 61  Bit Score: 60.41  E-value: 2.22e-11
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:cd11972    5 VVAIYDYTKDKEDELSFQEGAIIYVIKKNDDGWYEGVMNGVTGLFPGNYVESI 57
SH3_MYO15 cd11884
Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to ...
11-60 3.16e-11

Src Homology 3 domain of Myosin XV; This subfamily is composed of proteins with similarity to Myosin XVa. Myosin XVa is an unconventional myosin that is critical for the normal growth of mechanosensory stereocilia of inner ear hair cells. Mutations in the myosin XVa gene are associated with nonsyndromic hearing loss. Myosin XVa contains a unique N-terminal extension followed by a motor domain, light chain-binding IQ motifs, and a tail consisting of a pair of MyTH4-FERM tandems separated by a SH3 domain, and a PDZ 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: 212817  Cd Length: 56  Bit Score: 59.65  E-value: 3.16e-11
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVE---EGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11884    2 VVAVRAYITRDQTLLSFHKGDVIKLLPKEgplDPGWLFGTLDGRSGAFPKEYV 54
SH3_SH3YL1_like cd11841
Src homology 3 domain of SH3 domain containing Ysc84-like 1 (SH3YL1) protein; SH3YL1 localizes ...
10-60 3.17e-11

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: 59.71  E-value: 3.17e-11
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gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHV-TRVE-EGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11841    1 EVTALYSFEGQQPCDLSFQAGDRITVlTRTDsQFDWWEGRLRGRVGIFPANYV 53
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
25-60 4.30e-11

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  Cd Length: 52  Bit Score: 59.06  E-value: 4.30e-11
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gi 166064038  25 LSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11829   17 LSFEAGELIRVLQAPDGGWWEGEKDGLRGWFPASYV 52
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
12-60 5.56e-11

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  Cd Length: 53  Bit Score: 58.90  E-value: 5.56e-11
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gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11782    3 RAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYV 51
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
314-400 7.23e-11

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: 59.87  E-value: 7.23e-11
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gi 166064038   314 GSEEKNERYLLLFPNVLLMLSASPRMSGFIYQGKLPTTGMTITKLEDSEN--HRNAFEISGSMIERILVSCNNQQDLQEW 391
Cdd:smart00233  14 GKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSskKPHCFEIKTSDRKTLLLQAESEEEREKW 93

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gi 166064038   392 VEHLQKQTK 400
Cdd:smart00233  94 VEALRKAIA 102
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
11-59 8.29e-11

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  Cd Length: 53  Bit Score: 58.48  E-value: 8.29e-11
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNG---RTGWFPSNY 59
Cdd:cd11821    2 VRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGdpsRRGVFPVSF 53
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
14-62 8.79e-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: 58.48  E-value: 8.79e-11
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gi 166064038  14 KFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11902    6 KFAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIGWFPSNYVVE 54
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
15-61 9.00e-11

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  Cd Length: 56  Bit Score: 58.37  E-value: 9.00e-11
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gi 166064038  15 FNFQQTNEDELSFSKGDVIHVTRVE--EGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd12057    6 FPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNGRRGVFPDNFVK 54
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
13-60 9.82e-11

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  Cd Length: 53  Bit Score: 58.20  E-value: 9.82e-11
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVI-HVTRVEEGgWWEGTLNGRTGWFPSNYV 60
Cdd:cd11959    4 ALYDYQAADDDEISFDPDDIItNIEMIDEG-WWRGVCRGKYGLFPANYV 51
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
11-60 1.08e-10

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: 58.27  E-value: 1.08e-10
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11951    2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISGRVGFFPRNYV 51
SH3_Pex13p_fungal cd11771
Src Homology 3 domain of fungal peroxisomal membrane protein Pex13p; Pex13p, located in the ...
11-60 1.14e-10

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  Cd Length: 60  Bit Score: 58.06  E-value: 1.14e-10
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gi 166064038  11 VRAKFNFQQTN-EDELSFSKGDVIHVTRV-----EEGGWWEG-TLNGRTGWFPSNYV 60
Cdd:cd11771    2 CRALYDFTPENpEMELSLKKGDIVAVLSKtdplgRDSEWWKGrTRDGRIGWFPSNYV 58
SH3_Ysc84p_like cd11842
Src homology 3 domain of Ysc84p and similar fungal proteins; This family is composed of the ...
11-62 1.35e-10

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  Cd Length: 55  Bit Score: 57.82  E-value: 1.35e-10
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGG--WWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11842    2 AVALYDFAGEQPGDLAFQKGDIITILKKSDSQndWWTGRIGGREGIFPANYVEL 55
SH3_Intersectin2_1 cd11988
First Src homology 3 domain (or SH3A) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
12-60 1.36e-10

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  Cd Length: 57  Bit Score: 57.96  E-value: 1.36e-10
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gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHV--TRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11988    5 RALYPFEARNHDEMSFNAGDIIQVdeKTVGEPGWLYGSFQGNFGWFPCNYV 55
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
11-60 1.39e-10

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  Cd Length: 54  Bit Score: 57.86  E-value: 1.39e-10
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11820    3 VRALYDFEAAEDNELTFKAGEIITVLDDSDPNWWKGSNHRGEGLFPANFV 52
SH3_VAV2_2 cd11977
C-terminal (or second) Src homology 3 domain of VAV2 protein; VAV2 is widely expressed and ...
13-62 1.49e-10

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  Cd Length: 58  Bit Score: 57.71  E-value: 1.49e-10
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHV-TRVE-EGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11977    5 ARYNFAARDMRELSLREGDVVRIySRIGgDQGWWKGETNGRIGWFPSTYVEE 56
SH3_GRAP_N cd11948
N-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
13-61 1.87e-10

N-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 N-terminal SH3 domain of the related protein 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: 212881  Cd Length: 54  Bit Score: 57.52  E-value: 1.87e-10
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEG-GWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11948    4 ALYSFQATESDELPFQKGDILKILNMEDDqNWYKAELQGREGYIPKNYIK 53
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
12-62 2.18e-10

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  Cd Length: 55  Bit Score: 57.40  E-value: 2.18e-10
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gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRT--GWFPSNYVRE 62
Cdd:cd11858    3 KALYDFAGSVANELSLKKDDIVYIVQKEDNGWWLAKKLDESkeGWVPAAYLEE 55
SH3_ephexin1_like cd11793
Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange ...
11-62 2.28e-10

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  Cd Length: 55  Bit Score: 57.35  E-value: 2.28e-10
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGT--LNGRTGWFPSNYVRE 62
Cdd:cd11793    2 VQCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGErlRDGERGWFPSSYTEE 55
SH3_Src_like cd11845
Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members ...
10-59 3.36e-10

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  Cd Length: 52  Bit Score: 56.82  E-value: 3.36e-10
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gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTL--NGRTGWFPSNY 59
Cdd:cd11845    1 IYVALYDYEARTDDDLSFKKGDRLQILDDSDGDWWLARHlsTGKEGYIPSNY 52
SH3_MLK1-3 cd12059
Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3; MLKs 1, 2, and 3 are Serine ...
13-61 3.73e-10

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: 56.70  E-value: 3.73e-10
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVE-----EGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd12059    4 AVFDYEASAEDELTLRRGDRVEVLSKDsavsgDEGWWTGKINDRVGIFPSNYVT 57
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
11-63 5.14e-10

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  Cd Length: 59  Bit Score: 56.18  E-value: 5.14e-10
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:cd11971    2 VVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGVTGLFPGNYVESI 54
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
16-62 6.15e-10

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  Cd Length: 53  Bit Score: 55.72  E-value: 6.15e-10
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gi 166064038  16 NFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11856    7 DYEAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGDKEGWVPASYLEP 53
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
12-60 6.17e-10

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  Cd Length: 54  Bit Score: 55.78  E-value: 6.17e-10
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gi 166064038  12 RAKFNFQQTNEDELSFSKGDVI-HVTRVEEGgWWEGTLN-GRTGWFPSNYV 60
Cdd:cd11819    3 KALYDYQAAEDNEISFVEGDIItQIEQIDEG-WWLGVNAkGQKGLFPANYV 52
SH3_Vinexin_1 cd11921
First Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3) ...
12-60 6.53e-10

First 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: 212854  Cd Length: 55  Bit Score: 56.08  E-value: 6.53e-10
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11921    4 RLKFDFQAQSPKELTLQKGDIVYIHKEVDKNWLEGEHHGRVGIFPANYV 52
SH3_GRB2_N cd11946
N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical ...
13-61 7.94e-10

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  Cd Length: 56  Bit Score: 55.80  E-value: 7.94e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVE-EGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11946    5 AKYDFKATADDELSFKRGDILKVLNEEcDQNWYKAELNGKDGFIPKNYIE 54
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
11-62 8.31e-10

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  Cd Length: 53  Bit Score: 55.61  E-value: 8.31e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11961    2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHGSRGLFPSNYVEL 53
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
11-60 9.95e-10

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  Cd Length: 55  Bit Score: 55.41  E-value: 9.95e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVE-EGGWWEG-TLNGRTGWFPSNYV 60
Cdd:cd11763    2 VRALYDFDSQPSGELSLRAGEVLTITRQDvGDGWLEGrNSRGEVGLFPSSYV 53
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
11-60 1.16e-09

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  Cd Length: 53  Bit Score: 55.12  E-value: 1.16e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVI-HVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11843    2 VRALYDYEGQESDELSFKAGDILtKLEEEDEQGWCKGRLDGRVGLYPANYV 52
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
23-61 1.31e-09

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: 55.08  E-value: 1.31e-09
                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 166064038  23 DELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11828   14 EELGFKAGDVIEVLDMSDKDWWWGSIRDEEGWFPASFVR 52
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
13-61 1.41e-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  Cd Length: 55  Bit Score: 54.84  E-value: 1.41e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  13 AKFNFQQTNEDELSFSKGDVI-HVTRVEEGgWWEGTLNGRTGWFPSNYVR 61
Cdd:cd12073    5 ALYDYQGEGDDEISFDPQETItDIEMVDEG-WWKGTCHGHRGLFPANYVE 53
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
11-60 1.66e-09

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  Cd Length: 52  Bit Score: 54.82  E-value: 1.66e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTL-NGRTGWFPSNYV 60
Cdd:cd11812    2 VVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLvNGQQGYFPANYV 52
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
11-60 1.70e-09

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  Cd Length: 54  Bit Score: 54.71  E-value: 1.70e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVI-HVTRVEEgGWWEGTL-NGRTGWFPSNYV 60
Cdd:cd11960    2 ARALYDYQAADDTEISFDPGDIItDIEQIDE-GWWRGTGpDGTYGLFPANYV 52
SH3_CRK_N cd11758
N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor ...
11-62 2.34e-09

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  Cd Length: 55  Bit Score: 54.29  E-value: 2.34e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEG-TLNGRTGWFPSNYVRE 62
Cdd:cd11758    3 VRALFDFPGNDDEDLPFKKGEILTVIRKPEEQWWNArNSEGKTGMIPVPYVEK 55
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
9-63 2.82e-09

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  Cd Length: 55  Bit Score: 54.25  E-value: 2.82e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 166064038   9 LVVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63
Cdd:cd11920    1 LPARAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHGRVGIFPISYVEKL 55
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
13-61 3.01e-09

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: 53.86  E-value: 3.01e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRvEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11992    4 ALYPYSSSEPGDLTFNEGEEILVTQ-KDGEWWTGSIEDRTGIFPSNYVR 51
SH3_Intersectin1_1 cd11987
First Src homology 3 domain (or SH3A) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
12-59 3.31e-09

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  Cd Length: 55  Bit Score: 53.85  E-value: 3.31e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEG--GWWEGTLNGRTGWFPSNY 59
Cdd:cd11987    3 RALYPFEARSHDEITIQPGDIVMVDESQTGepGWLGGELKGKTGWFPANY 52
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
11-59 3.95e-09

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  Cd Length: 51  Bit Score: 53.66  E-value: 3.95e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEG-GWWEGTLNGRTGWFPSNY 59
Cdd:cd11778    2 VEALYDYEAQGDDEISIRVGDRIAVIRGDDGsGWTYGEINGVKGLFPTSY 51
SH3_Sho1p cd11855
Src homology 3 domain of High osmolarity signaling protein Sho1p; Sho1p (or Sho1), also called ...
11-61 4.19e-09

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  Cd Length: 55  Bit Score: 53.58  E-value: 4.19e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 166064038  11 VRAKFNFQQTNED--ELSFSKGDVIHVTRvEEGGWWEGTL-NGRTGWFPSNYVR 61
Cdd:cd11855    2 ARALYPYDASPDDpnELSFEKGEILEVSD-TSGKWWQARKsNGETGICPSNYLQ 54
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
11-60 4.31e-09

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  Cd Length: 55  Bit Score: 53.41  E-value: 4.31e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11964    3 VRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGETPQGTGLFPSNFV 52
SH3_Nebulin_family_C cd11789
C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins ...
10-60 4.38e-09

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  Cd Length: 55  Bit Score: 53.47  E-value: 4.38e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVI-HVTRVEEgGWWEGTL--NGRTGWFPSNYV 60
Cdd:cd11789    1 RYRAMYDYAAADDDEVSFQEGDVIiNVEIIDD-GWMEGTVqrTGQSGMLPANYV 53
SH3_FCHSD2_2 cd11894
Second Src Homology 3 domain of FCH and double SH3 domains protein 2; FCHSD2 has a domain ...
11-62 4.59e-09

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: 53.40  E-value: 4.59e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVE---EGGWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11894    2 VKALYDYEGQTDDELSFPEGAIIRILNKEnqdDDGFWEGEFNGRIGVFPSVLVEE 56
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
12-60 5.55e-09

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  Cd Length: 51  Bit Score: 53.18  E-value: 5.55e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11816    3 VARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51
SH3_Shank3 cd11984
Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also ...
22-60 6.25e-09

Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3; Shank3, also called ProSAP2 (Proline-rich synapse-associated protein 2), is widely expressed. It plays a role in the formation of dendritic spines and synapses. Haploinsufficiency of the Shank3 gene causes the 22q13 deletion/Phelan-McDermid syndrome, and variants of Shank3 have been implicated in autism spectrum disorder, schizophrenia, and intellectual disability. 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: 212917  Cd Length: 52  Bit Score: 53.03  E-value: 6.25e-09
                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 166064038  22 EDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11984   14 EGEIQLNRGERVKVLSIGEGGFWEGTVKGRTGWFPADCV 52
SH3_PSTPIP1 cd11824
Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, ...
12-60 9.73e-09

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  Cd Length: 53  Bit Score: 52.38  E-value: 9.73e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11824    3 SVLYDYTAQEDDELSISKGDVVAVIEKGEDGWWTVERNGQKGLVPGTYL 51
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
11-62 1.44e-08

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: 52.11  E-value: 1.44e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHV-TRVEEGgWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd12046    2 VVALFSYEASQPEDLEFQKGDVILVlSKVNED-WLEGQCKGKIGIFPSAFVED 53
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
13-59 2.38e-08

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  Cd Length: 50  Bit Score: 51.33  E-value: 2.38e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNY 59
Cdd:cd11817    4 ALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50
SH3_GRAP2_N cd11947
N-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
12-60 2.51e-08

N-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 have 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 N-terminal SH3 domain of the related protein 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: 212880  Cd Length: 52  Bit Score: 51.33  E-value: 2.51e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEgGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11947    3 RGKFDFTASGEDELSFKKGDVLKILSSDD-IWFKAELNGEEGYVPKNFV 50
SH3_MLK4 cd12058
Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), ...
13-60 2.81e-08

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  Cd Length: 58  Bit Score: 51.09  E-value: 2.81e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVE-----EGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd12058    4 ALYDYEASGEDELSLRRGDVVEVLSQDaavsgDDGWWAGKIRHRLGIFPANYV 56
SH3_PEX13_eumet cd11864
Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and ...
10-61 2.93e-08

Src Homology 3 domain of eumetazoan Peroxisomal biogenesis factor 13; PEX13 is a peroxin and is required for protein import into the peroxisomal matrix and membrane. It is an integral membrane protein that is essential for the localization of PEX14 and the import of proteins containing the peroxisome matrix targeting signals, PTS1 and PTS2. Mutations of the PEX13 gene in humans lead to a wide range of peroxisome biogenesis disorders (PBDs), the most severe of which is known as Zellweger syndrome (ZS), a severe multisystem disorder characterized by hypotonia, psychomotor retardation, and neuronal migration defects. PEX13 contains two transmembrane regions 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: 212798  Cd Length: 58  Bit Score: 51.09  E-value: 2.93e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEG----GWWEGTLNG-RTGWFPSNYVR 61
Cdd:cd11864    1 VARAEYDFVAESEDELSFRAGDKLRLAPKELQprvrGWLLATVDGqKIGLVPANYVK 57
SH3_srGAP cd11809
Src homology 3 domain of Slit-Robo GTPase Activating Proteins; Slit-Robo GTPase Activating ...
13-60 3.63e-08

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  Cd Length: 53  Bit Score: 50.86  E-value: 3.63e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11809    4 AQFDYTGRSERELSFKKGDSLTLYRQVSDDWWRGQLNGQDGLVPHKYI 51
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
11-60 3.77e-08

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  Cd Length: 57  Bit Score: 50.79  E-value: 3.77e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11963    4 VRALYDFEAVEDNELTFKHGEIIIVLDDSDANWWKGENHRGVGLFPSNFV 53
SH3_p40phox cd11869
Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil ...
13-61 3.88e-08

Src Homology 3 domain of the p40phox subunit of NADPH oxidase; p40phox, also called Neutrophil cytosol factor 4 (NCF-4), 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. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. It contains an N-terminal PX domain, a central SH3 domain, and a C-terminal PB1 domain that interacts with p67phox. The SH3 domain of p40phox binds to canonical polyproline and noncanonical motifs at the C-terminus of p47phox. 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: 212802  Cd Length: 54  Bit Score: 50.57  E-value: 3.88e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd11869    4 ALFDFTGNSKLELNFKAGDVIFLLSRVNKDWLEGTVRGATGIFPLSFVK 52
SH3_PRMT2 cd11806
Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, ...
10-60 4.78e-08

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding 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: 212740  Cd Length: 53  Bit Score: 50.47  E-value: 4.78e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11806    1 EYVAIADFVATDDSQLSFESGDKLLVLRKPSVDWWWAEHNGCCGYIPASHL 51
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
11-63 5.57e-08

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  Cd Length: 64  Bit Score: 50.40  E-value: 5.57e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVE-----EGGWWEGTL--NGRTGWFPSNYVREV 63
Cdd:cd11790    5 VRATHDYTAEDTDELTFEKGDVILVIPFDdpeeqDEGWLMGVKesTGCRGVFPENFTERI 64
SH3_Sorbs1_1 cd11919
First Src Homology 3 domain of Sorbin and SH3 domain containing 1 (Sorbs1), also called ponsin; ...
12-60 5.61e-08

First 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: 212852  Cd Length: 55  Bit Score: 50.35  E-value: 5.61e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11919    4 RAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYI 52
SH3_Fyn_Yrk cd12006
Src homology 3 domain of Fyn and Yrk Protein Tyrosine Kinases; Fyn and Yrk (Yes-related kinase) ...
13-60 6.25e-08

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  Cd Length: 56  Bit Score: 50.05  E-value: 6.25e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGT--LNGRTGWFPSNYV 60
Cdd:cd12006    5 ALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARslTTGETGYIPSNYV 54
SH3_CSK cd11769
Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr ...
13-62 6.65e-08

Src Homology 3 domain of C-terminal Src kinase; CSK is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, CSK is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. CSK catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. It is expressed in a wide variety of tissues and plays a role, as a regulator of Src, in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. In addition, CSK also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. 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: 212703  Cd Length: 57  Bit Score: 49.99  E-value: 6.65e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRV-EEGGWWEG-TLNGRTGWFPSNYVRE 62
Cdd:cd11769    6 AKYNFNGASEEDLPFKKGDILTIVAVtKDPNWYKAkNKDGREGMIPANYVQK 57
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
12-60 6.74e-08

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: 50.19  E-value: 6.74e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYV 60
Cdd:cd11813    3 KALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFV 51
SH3_iASPP cd11952
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ...
10-59 7.69e-08

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: 49.93  E-value: 7.69e-08
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gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVIHVTR--VEEGGWWEGTLNGRTGWFPSNY 59
Cdd:cd11952    2 VVYALWDYSAEFPDELSFKEGDMVTVLRkdGEGTDWWWASLCGREGYVPRNY 53
SH3_GRAF2 cd12065
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also ...
12-61 8.84e-08

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 2; GRAF2, also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA. It regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle, and is involved in alpha-catenin recruitment at cell-cell junctions. GRAF2 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: 212998  Cd Length: 54  Bit Score: 49.60  E-value: 8.84e-08
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gi 166064038  12 RAKFNFQQTNEDELSFSKGDVIH-VTRVEEGGWWEGTLNGRTGWFPSNYVR 61
Cdd:cd12065    3 KAVYPCEAEHSSELSFEVGAIFEdVTLSREPGWLEGTLNGKRGLIPENYVE 53
SH3_Cyk3p-like cd11889
Src Homology 3 domain of Cytokinesis protein 3 and similar proteins; Cytokinesis protein 3 ...
11-60 9.06e-08

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: 49.80  E-value: 9.06e-08
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gi 166064038  11 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTL--NGRTGWFPSNYV 60
Cdd:cd11889    2 VKAVYSWAGETEGDLGFLEGDLIEVLSIGDGSWWSGKLrrNGAEGIFPSNFV 53
SH3_Nebulin_C cd11933
C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 ...
10-63 9.69e-08

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  Cd Length: 58  Bit Score: 49.62  E-value: 9.69e-08
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gi 166064038  10 VVRAKFNFQQTNEDELSFSKGDVI-HVTRVEEgGWWEGTLN--GRTGWFPSNYVREV 63
Cdd:cd11933    3 SFRAMYDYRAADDDEVSFKDGDTIvNVQTIDE-GWMYGTVQrtGKTGMLPANYVEAI 58
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
13-62 1.12e-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  Cd Length: 58  Bit Score: 49.43  E-value: 1.12e-07
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEG-----GWWEGTLNGRTGWFPSNYVRE 62
Cdd:cd11876    4 ALFDYDARGEDELTLRRGQPVEVLSKDAAvsgdeGWWTGKIGDKVGIFPSNYVAP 58
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
278-397 1.38e-07

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. 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: 269931  Cd Length: 138  Bit Score: 50.34  E-value: 1.38e-07
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gi 166064038 278 ELE-LQILTEAIRNWEGDDIKTlgnvtymSQVLIQCAGSEEKN------ERYLLLFPNVLLMLSASP-RMSGFIYQGKLP 349
Cdd:cd01224    3 NLEkLAAWQSTVEGWEGEDLSD-------RSSELIHSGELTKIsagraqERTFFLFDHQLVYCKKDLlRRKNYIYKGRID 75
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gi 166064038 350 TTGMTITKLEDSENH------RNAFEISGSMIER-ILVSCNNQQDLQEWVEHLQK 397
Cdd:cd01224   76 TDNMEIEDLPDGKDDesgvtvKNAWKIYNASKNKwYVLCAKSAEEKQRWLEAFAE 130
SH3_Yes cd12007
Src homology 3 domain of Yes Protein Tyrosine Kinase; Yes (or c-Yes) is a member of the Src ...
13-60 1.57e-07

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  Cd Length: 58  Bit Score: 49.26  E-value: 1.57e-07
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gi 166064038  13 AKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEG--TLNGRTGWFPSNYV 60
Cdd:cd12007    5 ALYDYEARTTEDLSFKKGERFQIINNTEGDWWEArsIATGKNGYIPSNYV 54
SH3_ASEF2 cd11974
Src homology 3 domain of APC-Stimulated guanine nucleotide Exchange Factor 2; ASEF2, also ...
21-61 1.60e-07

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: 48.91  E-value: 1.60e-07
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