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Conserved domains on  [gi|65301464|ref|NP_034156.2|]
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arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 isoform a [Mus musculus]

Protein Classification

BAR_ASAP1 and PH_ASAP domain-containing protein (domain architecture ID 11576990)

protein containing domains BAR_ASAP1, PH_ASAP, ArfGap, and SH3_ASAP1

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
54-268 1.11e-136

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1) is also known as DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. ASAP1 is an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6 However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


:

Pssm-ID: 153325  Cd Length: 215  Bit Score: 416.38  E-value: 1.11e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:cd07641    1 RNTVNVLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQALDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  134 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 213
Cdd:cd07641   81 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464  214 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 268
Cdd:cd07641  161 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 215
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
331-437 8.00e-60

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270071  Cd Length: 108  Bit Score: 202.21  E-value: 8.00e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  331 QLQGNKEYGSEKKGFLLKKSDG-IRKVWQRRKCAVKNGILTISHATSNRQPAKLNLLTCQVKPNAEDKKSFDLISHNRTY 409
Cdd:cd13251    1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                         90       100
                 ....*....|....*....|....*...
gi 65301464  410 HFQAEDEQDYIAWISVLTNSKEEALTMA 437
Cdd:cd13251   81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
454-570 1.27e-44

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


:

Pssm-ID: 307528  Cd Length: 117  Bit Score: 159.72  E-value: 1.27e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    454 KAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDI 533
Cdd:pfam01412    1 KEVLRELRKLPGNKVCADCGAPNPTWASLNLGIFICIRCSGVHRSLGVHISKVRSLTLDTWTPEQLEFMKAGGNDRANEY 80
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 65301464    534 MEANLpSPSPKPTPSSDMTVRKEYITAKYVDHRFSRK 570
Cdd:pfam01412   81 WEANL-PKPLPPPPSSDQEKRESFIRAKYVEKKFAEP 116
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1089-1145 1.84e-35

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


:

Pssm-ID: 212898  Cd Length: 57  Bit Score: 131.28  E-value: 1.84e-35
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 1145
Cdd:cd11965    1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 57
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
616-704 1.03e-17

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


:

Pssm-ID: 238125  Cd Length: 126  Bit Score: 82.43  E-value: 1.03e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  616 GETALHLAVRTADqtsLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYGKPECLKLLLRSKPTVDIVNQNGETALDIAKRL 695
Cdd:cd00204   40 GRTPLHLAAKNGH---LEIVKLLLEKGADVNARDKDGNTPLHLAARNGNLDVVKLLLKHGADVNARDKDGRTPLHLAAKN 116

                 ....*....
gi 65301464  696 KATQCEDLL 704
Cdd:cd00204  117 GHLEVVKLL 125
Atrophin-1 super family cl26464
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
740-1078 1.35e-07

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 331285  Cd Length: 3151  Bit Score: 56.10  E-value: 1.35e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   740 PSPIKKERSPRPQSFchSSSISPQDKLALPGFSTPRDKQR---LSYGAFTNQIFASTSTDLPTSPTSEAPPLPPrnagKG 816
Cdd:PHA03247 2674 AQASSPPQRPRRRAA--RPTVGSLTSLADPPPPPPTPEPAphaLVSATPLPPGPAAARQASPALPAAPAPPAVP----AG 2747
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   817 PTGPPSTLPLGT-QTSSGSSTLSKKRPPPPppGHKRTLSDPPSPLPHGPPNKGAIPWGNDVGPLSSSKTANKFEGLSQQA 895
Cdd:PHA03247 2748 PATPGGPARPARpPTTAGPPAPAPPAAPAA--GPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPA 2825
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   896 STSSAKTALGPRVLPKLPQKVAlrktetsHHLSLDRTNIPPETF------QKSSQLTELPQKPPLGELP----PKPVELA 965
Cdd:PHA03247 2826 GPLPPPTSAQPTAPPPPPGPPP-------PSLPLGGSVAPGGDVrrrppsRSPAAKPAAPARPPVRRLArpavSRSTESF 2898
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   966 PKPQVGELPPKPGELPPKPQLGDLPPKPQLSDLPPKPQMK-DLPPKPQLGdllaksqagdvSAKVQPPSEVTQRSHTGDL 1044
Cdd:PHA03247 2899 ALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRpQPPLAPTTD-----------PAGAGEPSGAVPQPWLGAL 2967
                         330       340       350
                  ....*....|....*....|....*....|....
gi 65301464  1045 SPnvqSRDAIQKQASEDSNDLTPTlPETPVPLPR 1078
Cdd:PHA03247 2968 VP---GRVAVPRFRVPQPAPSREA-PASSTPPLT 2997
 
Name Accession Description Interval E-value
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
54-268 1.11e-136

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1) is also known as DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. ASAP1 is an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6 However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153325  Cd Length: 215  Bit Score: 416.38  E-value: 1.11e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:cd07641    1 RNTVNVLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQALDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  134 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 213
Cdd:cd07641   81 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464  214 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 268
Cdd:cd07641  161 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 215
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
331-437 8.00e-60

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 202.21  E-value: 8.00e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  331 QLQGNKEYGSEKKGFLLKKSDG-IRKVWQRRKCAVKNGILTISHATSNRQPAKLNLLTCQVKPNAEDKKSFDLISHNRTY 409
Cdd:cd13251    1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                         90       100
                 ....*....|....*....|....*...
gi 65301464  410 HFQAEDEQDYIAWISVLTNSKEEALTMA 437
Cdd:cd13251   81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
454-570 1.27e-44

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 307528  Cd Length: 117  Bit Score: 159.72  E-value: 1.27e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    454 KAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDI 533
Cdd:pfam01412    1 KEVLRELRKLPGNKVCADCGAPNPTWASLNLGIFICIRCSGVHRSLGVHISKVRSLTLDTWTPEQLEFMKAGGNDRANEY 80
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 65301464    534 MEANLpSPSPKPTPSSDMTVRKEYITAKYVDHRFSRK 570
Cdd:pfam01412   81 WEANL-PKPLPPPPSSDQEKRESFIRAKYVEKKFAEP 116
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1089-1145 1.84e-35

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212898  Cd Length: 57  Bit Score: 131.28  E-value: 1.84e-35
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 1145
Cdd:cd11965    1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 57
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
460-567 3.15e-33

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518  Cd Length: 119  Bit Score: 127.07  E-value: 3.15e-33
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     460 VQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEANLP 539
Cdd:smart00105    4 LRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESNLD 83
                            90       100
                    ....*....|....*....|....*...
gi 65301464     540 SPSPKPTPSSDMTVRKEYITAKYVDHRF 567
Cdd:smart00105   84 DFSLKPPDDDDQQKYESFIAAKYEEKLF 111
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
447-567 4.67e-26

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651  Cd Length: 319  Bit Score: 111.79  E-value: 4.67e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  447 NSLEDLTKAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVG 526
Cdd:COG5347    1 MSTKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 65301464  527 NNSFNDIMEANLPSPSPKPTPSS-DMTVRKEYITAKYVDHRF 567
Cdd:COG5347   81 NSNANRFYEKNLLDQLLLPIKAKyDSSVAKKYIRKKYELKKF 122
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
54-286 6.69e-24

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 318867  Cd Length: 235  Bit Score: 103.40  E-value: 6.69e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGsnFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:pfam16746   14 RSLLEEHEADLEELEKKLKKLIKLCKRLIEAGKAYSAAQQAFAQSLLEFQ--FQFIGDEETDESLKKFSQLLQEMEDFHT 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    134 NLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYET---KFTKIEKEKREHAKQhgmirteitgaEIAEEMEKE 210
Cdd:pfam16746   92 ILLDQAQRTIIKPLEKFRKEDIGEVK-ETKKKFDKASEKLDAaleKNAQLSRKKKPSELE-----------EADNELDAT 159
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464    211 RRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKLAADLYNIKQTQDEEKKQL 286
Cdd:pfam16746  160 RKCFHHTALDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGHELFKDLEPYMKDLQAQLQNTREETAEEKEEL 235
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
616-704 1.03e-17

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 82.43  E-value: 1.03e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  616 GETALHLAVRTADqtsLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYGKPECLKLLLRSKPTVDIVNQNGETALDIAKRL 695
Cdd:cd00204   40 GRTPLHLAAKNGH---LEIVKLLLEKGADVNARDKDGNTPLHLAARNGNLDVVKLLLKHGADVNARDKDGRTPLHLAAKN 116

                 ....*....
gi 65301464  696 KATQCEDLL 704
Cdd:cd00204  117 GHLEVVKLL 125
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
1086-1142 7.28e-14

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: 69.49  E-value: 7.28e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464    1086 KVRRVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpERKGVFPVSFV 1142
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR--GKEGLFPSNYV 55
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
342-426 1.09e-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: 64.49  E-value: 1.09e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     342 KKGFLLKKSDGIRKVWQRRKCAVKNGILTI----SHATSNRQPAKLNLLTCQVKPNAE-----DKKSFDLISHNR-TYHF 411
Cdd:smart00233    3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYykskKDKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIKTSDRkTLLL 82
                            90
                    ....*....|....*
gi 65301464     412 QAEDEQDYIAWISVL 426
Cdd:smart00233   83 QAESEEEREKWVEAL 97
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
466-528 1.19e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661  Cd Length: 395  Bit Score: 67.96  E-value: 1.19e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 65301464   466 NDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNN 528
Cdd:PLN03114   22 NKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNN 84
Ank_2 pfam12796
Ankyrin repeats (3 copies);
620-692 1.62e-10

Ankyrin repeats (3 copies);


Pssm-ID: 315466  Cd Length: 92  Bit Score: 60.51  E-value: 1.62e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 65301464    620 LHLAVRtadQTSLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYGKPECLKLLLrSKPTVDIVNQNGETALDIA 692
Cdd:pfam12796    1 LHLAAK---NGDLELVKLLLEEGADANLQDKNGRTALHLAAKNGHLEIVKLLL-EHADVNLKDKNGRTALHYA 69
PH pfam00169
PH domain; PH stands for pleckstrin homology.
341-426 2.90e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 306640  Cd Length: 105  Bit Score: 57.19  E-value: 2.90e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    341 EKKGFLLKKSDGIRKVWQRRKCAVKNGILTI----SHATSNRQPAKLNLLTCQVK-----PNAEDKKSFDLI----SHNR 407
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYykddKSGKSKEPKGSISLSGCEVVevvapDSPKRKFCFELRtgerTGGR 81
                           90
                   ....*....|....*....
gi 65301464    408 TYHFQAEDEQDYIAWISVL 426
Cdd:pfam00169   82 TYLLQAESEEERKDWIKAI 100
SH3_9 pfam14604
Variant SH3 domain;
1093-1142 9.80e-09

Variant SH3 domain;


Pssm-ID: 291278  Cd Length: 50  Bit Score: 54.53  E-value: 9.80e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 65301464   1093 IYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQpeRKGVFPVSFV 1142
Cdd:pfam14604    2 LYPYEPRDDDELSLRRGDVITVLEESEDGWLLGSNTTG--RTGLVPANYV 49
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
509-726 5.26e-08

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 223738  Cd Length: 235  Bit Score: 54.83  E-value: 5.26e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  509 LELDKLGTSELLLAKNVGNNSFNDIMEANLPSPSPKPTPSSDMTVRKEYITAKYVDhrfsRKTCASSSAKLNELLEAIKS 588
Cdd:COG0666    8 LLLINKCFLDLLLVALLLLLSLDLSNPSDKKLNLYLELALLPAASLSELLLKLIVD----RHLAARDLDGRLPLHSAASK 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  589 RDLLALIQVYAEGVELmepllEPGQELGETALHLAVRTADQTSLH--LVDFLVQN---CGNLDKQTSVGNTVLHYCSMYG 663
Cdd:COG0666   84 GDDKIVKLLLASGADV-----NAKDADGDTPLHLAALNGNPPEGNieVAKLLLEAgadLDVNNLRDEDGNTPLHWAALNG 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464  664 KPECLKLLLRSKPTVDIVNQNGETALDIAKRLKATQCEDLLSQAKSG----KFNPHVHVEYEWNLRQ 726
Cdd:COG0666  159 DADIVELLLEAGADPNSRNSYGVTALDPAAKNGRIELVKLLLDKGLHlsllKFNLEGVANANVSKRN 225
PHA03247 PHA03247
large tegument protein UL36; Provisional
740-1078 1.35e-07

large tegument protein UL36; Provisional


Pssm-ID: 223021  Cd Length: 3151  Bit Score: 56.10  E-value: 1.35e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   740 PSPIKKERSPRPQSFchSSSISPQDKLALPGFSTPRDKQR---LSYGAFTNQIFASTSTDLPTSPTSEAPPLPPrnagKG 816
Cdd:PHA03247 2674 AQASSPPQRPRRRAA--RPTVGSLTSLADPPPPPPTPEPAphaLVSATPLPPGPAAARQASPALPAAPAPPAVP----AG 2747
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   817 PTGPPSTLPLGT-QTSSGSSTLSKKRPPPPppGHKRTLSDPPSPLPHGPPNKGAIPWGNDVGPLSSSKTANKFEGLSQQA 895
Cdd:PHA03247 2748 PATPGGPARPARpPTTAGPPAPAPPAAPAA--GPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPA 2825
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   896 STSSAKTALGPRVLPKLPQKVAlrktetsHHLSLDRTNIPPETF------QKSSQLTELPQKPPLGELP----PKPVELA 965
Cdd:PHA03247 2826 GPLPPPTSAQPTAPPPPPGPPP-------PSLPLGGSVAPGGDVrrrppsRSPAAKPAAPARPPVRRLArpavSRSTESF 2898
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   966 PKPQVGELPPKPGELPPKPQLGDLPPKPQLSDLPPKPQMK-DLPPKPQLGdllaksqagdvSAKVQPPSEVTQRSHTGDL 1044
Cdd:PHA03247 2899 ALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRpQPPLAPTTD-----------PAGAGEPSGAVPQPWLGAL 2967
                         330       340       350
                  ....*....|....*....|....*....|....
gi 65301464  1045 SPnvqSRDAIQKQASEDSNDLTPTlPETPVPLPR 1078
Cdd:PHA03247 2968 VP---GRVAVPRFRVPQPAPSREA-PASSTPPLT 2997
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
740-1082 2.09e-07

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 308660  Cd Length: 938  Bit Score: 55.10  E-value: 2.09e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    740 PSPIKKERS--------PRPQSFCHSSSISPQDKLALP---GFSTPRDKQRLSYGAFTNQIFASTSTDLPTSPTSEAPPL 808
Cdd:pfam03154  155 PSPMQANESdsdssappPPPGPGTQVQQPAPTPATPLPsqtPPPMTSQPQPLPVASPSTITTATSTTTTSRVVSPVDPNP 234
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    809 ------PPRNAGKGPTGPPSTLPlgtQTSSGSSTLSkkrppppppghkrtlsdppsplphgPPNKGAIPWGNDVGPLSSS 882
Cdd:pfam03154  235 dppsiiAPQSAQRGPEGPPTPQP---HSLQGPPSFP-------------------------GPAQGPGQGQGQSPPPPSL 286
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    883 KTANKFEGLSQQASTSSAKTALGPRVLPKLPQKVA----LRKTET-----SH----HLSLD-----RTNIPPETFQKSsq 944
Cdd:pfam03154  287 YPPHPNQLQSHPPSQGPHPTHSFPPKPVPLPPPPAsapqIKPPPTtpipsSHkhppHLSASpfpqmPSNLPPPPALKP-- 364
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    945 LTELPQKPPLGELPPkPVELAPKPQvgELPPKPGELPPKPQLGDLPPKPQLSDLPP-----KPQMKDLPPKPQLGDLLAK 1019
Cdd:pfam03154  365 LASLPSQHPPCAQPP-PLQLMPQPH--QLQPPPAQPPVLTQSQSHQVKGHHASPPPttaasHPSLSSTAPFPLSSASSVP 441
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 65301464   1020 SQAGDVSAKV------QPPSEVTQRSHTgdLSPNVQSRDaiQKQASEDSNDLTPTLPETPVPLPRKINT 1082
Cdd:pfam03154  442 GAVGPVPSPVpamsgpQPSSSSALSVST--VPPQLTIKE--EPLDEEEECESPPPPRRSPSPEPTIVNI 506
PHA03095 PHA03095
ankyrin-like protein; Provisional
614-691 9.10e-05

ankyrin-like protein; Provisional


Pssm-ID: 222980  Cd Length: 471  Bit Score: 46.17  E-value: 9.10e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 65301464   614 ELGETALHLAVRTADQTSLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYG-KPECLKLLLRSKPTVDIVNQNGETALDI 691
Cdd:PHA03095   45 EYGKTPLHLYLHYSSEKVKDIVRLLLEAGADVNAPERCGFTPLHLYLYNAtTLDVIKLLIKAGADVNAKDKVGRTPLHV 123
BAR smart00721
BAR domain;
42-265 7.39e-04

BAR domain;


Pssm-ID: 214787  Cd Length: 239  Bit Score: 42.37  E-value: 7.39e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464      42 TTSSFTTRLHNCRNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDH--VQNEENYAQVLDKFGSNFlsrdnpdlgtafv 119
Cdd:smart00721   38 TTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGGDDGegLGADSSYGKALDKLGEAL------------- 104
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     120 kfstltKELSTLLKNLLQGLsHNVIFTLDSLLKGDLKGVKGDLKKpFDKAWKDYETKFTKIEKEKREHAKQhgmIRTEIT 199
Cdd:smart00721  105 ------KKLLQVEESLSQVK-RTFILPLLNFLLGEFKEIKKARKK-LERKLLDYDSARHKLKKAKKSKEKK---KDEKLA 173
                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 65301464     200 GAEiaEEMEKERRLF---QLQMCEYLIKVNEIKTKKGVDLLQNLIKyyhAQCNFFQDGLKTADKLKQYI 265
Cdd:smart00721  174 KAE--EELRKAKQEFeesNAQLVEELPQLVASRVDFFVNCLQALIE---AQLNFHRESYKLLQQLQQQL 237
BchD-ChlD TIGR02031
magnesium chelatase ATPase subunit D; This model represents one of two ATPase subunits of the ...
931-1023 1.92e-03

magnesium chelatase ATPase subunit D; This model represents one of two ATPase subunits of the trimeric magnesium chelatase responsible for insertion of magnesium ion into protoporphyrin IX. This is an essential step in the biosynthesis of both chlorophyll and bacteriochlorophyll. This subunit is found in green plants, photosynthetic algae, cyanobacteria and other photosynthetic bacteria. Unlike subunit I (TIGR02030), this subunit is not found in archaea. [Biosynthesis of cofactors, prosthetic groups, and carriers, Chlorophyll and bacteriochlorphyll]


Pssm-ID: 273935  Cd Length: 589  Bit Score: 42.10  E-value: 1.92e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    931 RTNIPPETFQKSSQLTELPQKPPLGELPPKPVELAPKPQvgelPPKPGELPPKPQLGDLPPKPQLSDLPPKPQMK----D 1006
Cdd:TIGR02031  243 RTEVTEEDLKLAVELVLLPRATRLPEPEPQPPPPPPPPE----PPEPEEEPDEPDQTDPDDGEETDQIPEELMFDaveaD 318
                           90
                   ....*....|....*..
gi 65301464   1007 LPPkpqlgDLLAKSQAG 1023
Cdd:TIGR02031  319 LPD-----NILATLQTV 330
TonB COG0810
Periplasmic protein TonB, links inner and outer membranes [Cell wall/membrane/envelope ...
934-1052 2.99e-03

Periplasmic protein TonB, links inner and outer membranes [Cell wall/membrane/envelope biogenesis];


Pssm-ID: 223880  Cd Length: 244  Bit Score: 40.54  E-value: 2.99e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  934 IPPETFQKSSQltelPQKPPLGELPPKP-VELAPKPQVGELPPKPGELPPKPQlgdlPPKPQLSDLPPKPQMKDLPPKPQ 1012
Cdd:COG0810   47 KVLEAPTEEPQ----PEPEPPEEQPKPPtEPETPPEPTPPKPKEKPKPEKKPK----KPKPKPKPKPKPKPKVKPQPKPK 118
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 65301464 1013 L----GDLLAKSQagdVSAKVQPPSEVTQRSHTGDLSPNVQSRD 1052
Cdd:COG0810  119 KppskTAAKAPAA---PNQPARPPSAASASGAATGPSASYLSGL 159
trp TIGR00870
transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ ...
593-715 3.53e-03

transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ Channel (TRP-CC) Family (TC. 1.A.4)The TRP-CC family has also been called the store-operated calcium channel (SOC) family. The prototypical members include the Drosophila retinal proteinsTRP and TRPL (Montell and Rubin, 1989; Hardie and Minke, 1993). SOC members of the family mediate the entry of extracellular Ca2+ into cells in responseto depletion of intracellular Ca2+ stores (Clapham, 1996) and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CCfamily, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor (TC #1.A.3.2.1). This interaction is apparently required for IP3 tostimulate Ca2+ release via Htrp3. The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin (the ?hot? ingredient in chili peppers) and servesas a heat-activated ion channel in the pain pathway (Caterina et al., 1997), is also a member of this family. The stretch-inhibitable non-selective cation channel(SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SICtransport monovalent cations as well as Ca2+. VR1 is about 10x more permeable to Ca2+ than to monovalent ions. Ca2+ overload probably causes cell deathafter chronic exposure to capsaicin. (McCleskey and Gold, 1999). [Transport and binding proteins, Cations and iron carrying compounds]


Pssm-ID: 273311  Cd Length: 743  Bit Score: 41.22  E-value: 3.53e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    593 ALIQVYAEGVELMEPLLEPGQELGETALHLAVRTAdqtSLHLVDFLVQNCGNLDKQTSVGNTVLHYCSM-------YGKP 665
Cdd:TIGR00870  152 ASVPARACGDFFVKSQGVDSFYHGESPLNAAACLG---SPSIVALLSEDPADILTADSLGNTLLHLLVMenefkaeYEEL 228
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 65301464    666 EC------LKLLLRSKPTV---DIVNQNGETALDIAKRLKATQCEDLLSQAK--SGKFNPH 715
Cdd:TIGR00870  229 SCqmynfaLSLLDKLRDSKeleVILNHQGLTPLKLAAKEGRIVLFRLKLAIKykQKKFVAW 289
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
652-680 3.67e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603  Cd Length: 30  Bit Score: 37.95  E-value: 3.67e-03
                            10        20
                    ....*....|....*....|....*....
gi 65301464     652 GNTVLHYCSMYGKPECLKLLLRSKPTVDI 680
Cdd:smart00248    2 GRTPLHLAAENGNLEVVKLLLDKGADINA 30
Amelogenin smart00818
Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem ...
910-1002 5.21e-03

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins. Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units: the N-terminal region appears to contain beta-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive beta-turn segment and a "beta-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region. The beta-spiral offers a probable site for interactions with Ca2+ ions. Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide.


Pssm-ID: 197891  Cd Length: 165  Bit Score: 39.00  E-value: 5.21e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     910 PKLPQKVALRKTETSHHlsldRTNIPPETFQkssqltelPQKPPLGELPPKPVELAPKPQVGELPPKPGELPPKPQLGDL 989
Cdd:smart00818   72 PLMPVPGQHSMTPTQHH----QPNLPQPAQQ--------PFQPQPLQPPQPQQPMQPQPPVHPIPPLPPQPPLPPMFPMQ 139
                            90
                    ....*....|...
gi 65301464     990 PPKPQLSDLPPKP 1002
Cdd:smart00818  140 PLPPLLPDLPLEA 152
 
Name Accession Description Interval E-value
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
54-268 1.11e-136

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1) is also known as DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. ASAP1 is an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6 However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153325  Cd Length: 215  Bit Score: 416.38  E-value: 1.11e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:cd07641    1 RNTVNVLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQALDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  134 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 213
Cdd:cd07641   81 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464  214 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 268
Cdd:cd07641  161 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 215
BAR_ASAPs cd07604
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
54-268 1.91e-124

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ASAPs (ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) with similarity to ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins) in that they contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and ankyrin (ANK) repeats. However, ASAPs contain an additional C-terminal SH3 domain. ASAPs function in regulating cell growth, migration, and invasion. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3. ASAP1 and ASAP2 shows GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but is able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153288  Cd Length: 215  Bit Score: 384.07  E-value: 1.91e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:cd07604    1 RNTVGALEESLEGDRVGLQKLKKAVKAIHNSGLAHVENELQFAEALEKLGSKALSREEEDLGAAFLKFSVFTKELAALFK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  134 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 213
Cdd:cd07604   81 NLMQNLNNIIMFPLDSLLKGDLKGSKGDLKKPFDKAWKDYETKASKIEKEKKQLAKEAGMIRTEITGAEIAEEMEKERRM 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464  214 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 268
Cdd:cd07604  161 FQLQMCEYLIKVNEIKTKKGVDLLQHLVEYYHAQNSYFQDGLKVIEHFRPYIEKL 215
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
54-268 1.18e-114

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP2 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2) is also known as DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. ASAP2 mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153326  Cd Length: 215  Bit Score: 357.81  E-value: 1.18e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:cd07642    1 RNTVVAIEEALDVDRTVLYKMKKSVKAIHTSGLAHVENEEQYTQALEKFGSNCVCRDDPDLGSAFLKFSVFTKELTALFK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  134 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITGAEIAEEMEKERRL 213
Cdd:cd07642   81 NLVQNMNNIITFPLDSLLKGDLKGVKGDLKKPFDKAWKDYETKVTKIEKEKKEHAKMHGMIRTEISGAEIAEEMEKERRF 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464  214 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 268
Cdd:cd07642  161 FQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDGLKAVETLKPSIEKL 215
BAR_ASAP3 cd07640
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
54-268 6.64e-78

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP3 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 3) is also known as ACAP4 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 4), DDEFL1 (Development and Differentiation Enhancing Factor-Like 1), or centaurin beta-6. It is an Arf6-specific GTPase activating protein (GAP) and is co-localized with Arf6 in ruffling membranes upon EGF stimulation. ASAP3 is implicated in the pathogenesis of hepatocellular carcinoma and plays a role in regulating cell migration and invasion. ASAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153324  Cd Length: 213  Bit Score: 256.46  E-value: 6.64e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:cd07640    1 RSTAAALEESLEGDQASLQRIKKIVKAIHNSGLNHVENEEQYTEALENLGNSHLSQNNHELSTGFLNLAVFTREVTALFK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  134 NLLQGLSHNVIFTLDSLLKGDLKGVKGDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEITgaEIAEEMEKERRL 213
Cdd:cd07640   81 NLVQNLNNIVSFPLDSLLKGQLRDGRLESKKQMEKAWKDYEAKIGKLEKERREKQKQHGLIRLDMT--DTAEDMQRERRN 158
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464  214 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKL 268
Cdd:cd07640  159 FQLHMCEYLLKAQESQMKQGPDFLQSLIKFFHAQHNFFQDGWKAAQNLGPFIEKL 213
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
331-437 8.00e-60

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270071  Cd Length: 108  Bit Score: 202.21  E-value: 8.00e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  331 QLQGNKEYGSEKKGFLLKKSDG-IRKVWQRRKCAVKNGILTISHATSNRQPAKLNLLTCQVKPNAEDKKSFDLISHNRTY 409
Cdd:cd13251    1 QQQGNKSHGTEKSGYLLKKSEGkIRKVWQKRRCSIKDGFLTISHADENKPPAKLNLLTCQVKLVPEDKKCFDLISHNRTY 80
                         90       100
                 ....*....|....*....|....*...
gi 65301464  410 HFQAEDEQDYIAWISVLTNSKEEALTMA 437
Cdd:cd13251   81 HFQAEDENDANAWMSVLKNSKEQALNKA 108
ArfGap pfam01412
Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating ...
454-570 1.27e-44

Putative GTPase activating protein for Arf; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 307528  Cd Length: 117  Bit Score: 159.72  E-value: 1.27e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    454 KAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDI 533
Cdd:pfam01412    1 KEVLRELRKLPGNKVCADCGAPNPTWASLNLGIFICIRCSGVHRSLGVHISKVRSLTLDTWTPEQLEFMKAGGNDRANEY 80
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 65301464    534 MEANLpSPSPKPTPSSDMTVRKEYITAKYVDHRFSRK 570
Cdd:pfam01412   81 WEANL-PKPLPPPPSSDQEKRESFIRAKYVEKKFAEP 116
SH3_ASAP1 cd11965
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1089-1145 1.84e-35

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 1; ASAP1 is also called DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6. However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212898  Cd Length: 57  Bit Score: 131.28  E-value: 1.84e-35
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 1145
Cdd:cd11965    1 RVKTIYDCQADNDDELTFVEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVHIL 57
ArfGap smart00105
Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with ...
460-567 3.15e-33

Putative GTP-ase activating proteins for the small GTPase, ARF; Putative zinc fingers with GTPase activating proteins (GAPs) towards the small GTPase, Arf. The GAP of ARD1 stimulates GTPase hydrolysis for ARD1 but not ARFs.


Pssm-ID: 214518  Cd Length: 119  Bit Score: 127.07  E-value: 3.15e-33
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     460 VQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNNSFNDIMEANLP 539
Cdd:smart00105    4 LRSIPGNKKCFDCGAPNPTWASVNLGVFLCIECSGIHRSLGVHISKVRSLTLDTWTEEELRLLQKGGNENANSIWESNLD 83
                            90       100
                    ....*....|....*....|....*...
gi 65301464     540 SPSPKPTPSSDMTVRKEYITAKYVDHRF 567
Cdd:smart00105   84 DFSLKPPDDDDQQKYESFIAAKYEEKLF 111
SH3_ASAP cd11821
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1089-1141 4.67e-33

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: 124.35  E-value: 4.67e-33
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSF 1141
Cdd:cd11821    1 RVRALYDCQADNDDELTFSEGEIIVVTGEEDDEWWEGHIEGDPSRRGVFPVSF 53
BAR cd07307
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
64-264 7.41e-32

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


Pssm-ID: 153271  Cd Length: 194  Bit Score: 125.63  E-value: 7.41e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   64 LDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFLSRDNPDLGTAFVKFSTLTKELSTLLKNLLQGLSHNV 143
Cdd:cd07307    2 LDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPDLSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  144 IFTLDSLLKGDLKGVKgDLKKPFDKAWKDYETKFTKIEKEKREHAKQHGMIRTEitgaeiaEEMEKERRLFQLQMCEYLI 223
Cdd:cd07307   82 IEPLKEYLKKDLKEIK-KRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEAE-------EELQEAKEKYEELREELIE 153
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 65301464  224 KVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQY 264
Cdd:cd07307  154 DLNKLEEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLLPY 194
SH3_ASAP2 cd11966
Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing ...
1089-1143 2.13e-28

Src homology 3 domain of ArfGAP with SH3 domain, ankyrin repeat and PH domain containing protein 2; ASAP2 is also called DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. It mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and it binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212899  Cd Length: 56  Bit Score: 111.20  E-value: 2.13e-28
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERKGVFPVSFVH 1143
Cdd:cd11966    1 RVKALYNCVADNPDELTFSEGEIIIVDGEEDKEWWIGHIDGEPTRRGAFPVSFVH 55
COG5347 COG5347
GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ...
447-567 4.67e-26

GTPase-activating protein that regulates ARFs (ADP-ribosylation factors), involved in ARF-mediated vesicular transport [Intracellular trafficking and secretion];


Pssm-ID: 227651  Cd Length: 319  Bit Score: 111.79  E-value: 4.67e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  447 NSLEDLTKAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVG 526
Cdd:COG5347    1 MSTKSEDRKLLKLLKSDSSNKKCADCGAPNPTWASVNLGVFLCIDCAGVHRSLGVHISKVKSLTLDNWTEEELRRMEVGG 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 65301464  527 NNSFNDIMEANLPSPSPKPTPSS-DMTVRKEYITAKYVDHRF 567
Cdd:COG5347   81 NSNANRFYEKNLLDQLLLPIKAKyDSSVAKKYIRKKYELKKF 122
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
54-286 6.69e-24

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 318867  Cd Length: 235  Bit Score: 103.40  E-value: 6.69e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGsnFLSRDNPDLGTAFVKFSTLTKELSTLLK 133
Cdd:pfam16746   14 RSLLEEHEADLEELEKKLKKLIKLCKRLIEAGKAYSAAQQAFAQSLLEFQ--FQFIGDEETDESLKKFSQLLQEMEDFHT 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    134 NLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYET---KFTKIEKEKREHAKQhgmirteitgaEIAEEMEKE 210
Cdd:pfam16746   92 ILLDQAQRTIIKPLEKFRKEDIGEVK-ETKKKFDKASEKLDAaleKNAQLSRKKKPSELE-----------EADNELDAT 159
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464    211 RRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYIEKLAADLYNIKQTQDEEKKQL 286
Cdd:pfam16746  160 RKCFHHTALDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQGHELFKDLEPYMKDLQAQLQNTREETAEEKEEL 235
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
616-704 1.03e-17

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 82.43  E-value: 1.03e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  616 GETALHLAVRTADqtsLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYGKPECLKLLLRSKPTVDIVNQNGETALDIAKRL 695
Cdd:cd00204   40 GRTPLHLAAKNGH---LEIVKLLLEKGADVNARDKDGNTPLHLAARNGNLDVVKLLLKHGADVNARDKDGRTPLHLAAKN 116

                 ....*....
gi 65301464  696 KATQCEDLL 704
Cdd:cd00204  117 GHLEVVKLL 125
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
616-692 4.37e-16

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 77.81  E-value: 4.37e-16
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464  616 GETALHLAVRTADqtsLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYGKPECLKLLLRSKPTVDIVNQNGETALDIA 692
Cdd:cd00204    7 GRTPLHLAASNGH---LEVVKLLLENGADVNAKDNDGRTPLHLAAKNGHLEIVKLLLEKGADVNARDKDGNTPLHLA 80
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
342-435 1.79e-14

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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: 270070  Cd Length: 98  Bit Score: 72.25  E-value: 1.79e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  342 KKGFLLKKSDGIRKVWQRRKCAVKNGILTISHATSNRQPAKL--NLLTCQVKPNAE-DKK-SFDLISHNRTYHFQAEDEQ 417
Cdd:cd13250    1 KEGYLFKRSSNAFKTWKRRWFSLQNGQLYYQKRDKKDEPTVMveDLRLCTVKPTEDsDRRfCFEVISPTKSYMLQAESEE 80
                         90
                 ....*....|....*...
gi 65301464  418 DYIAWISVLTNSKEEALT 435
Cdd:cd13250   81 DRQAWIQAIQSAIASALN 98
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
1086-1142 7.28e-14

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: 69.49  E-value: 7.28e-14
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464    1086 KVRRVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpERKGVFPVSFV 1142
Cdd:smart00326    1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR--GKEGLFPSNYV 55
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
1089-1141 7.81e-14

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: 69.41  E-value: 7.81e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQpeRKGVFPVSF 1141
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNGG--REGLFPANY 51
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
342-426 1.09e-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: 64.49  E-value: 1.09e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464     342 KKGFLLKKSDGIRKVWQRRKCAVKNGILTI----SHATSNRQPAKLNLLTCQVKPNAE-----DKKSFDLISHNR-TYHF 411
Cdd:smart00233    3 KEGWLYKKSGGGKKSWKKRYFVLFNSTLLYykskKDKKSYKPKGSIDLSGCTVREAPDpdsskKPHCFEIKTSDRkTLLL 82
                            90
                    ....*....|....*
gi 65301464     412 QAEDEQDYIAWISVL 426
Cdd:smart00233   83 QAESEEEREKWVEAL 97
PLN03114 PLN03114
ADP-ribosylation factor GTPase-activating protein AGD10; Provisional
466-528 1.19e-11

ADP-ribosylation factor GTPase-activating protein AGD10; Provisional


Pssm-ID: 178661  Cd Length: 395  Bit Score: 67.96  E-value: 1.19e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 65301464   466 NDICCDCGSSEPTWLSTNLGILTCIECSGIHREMGVHISRIQSLELDKLGTSELLLAKNVGNN 528
Cdd:PLN03114   22 NKICFDCNAKNPTWASVTYGIFLCIDCSAVHRSLGVHISFVRSTNLDSWSSEQLKMMIYGGNN 84
BAR_ACAPs cd07603
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
50-265 1.79e-11

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) containing an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. Vertebrates contain at least three members, ACAP1, ACAP2, and ACAP3. ACAP1 and ACAP2 are Arf6-specific GAPs, involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration, by mediating Arf6 signaling. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153287  Cd Length: 200  Bit Score: 65.02  E-value: 1.79e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   50 LHNCRNTVTLLEEALDqdrtalqKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFlsRDNPDLGTAFVKFSTLTKELS 129
Cdd:cd07603    4 LEQVEADVSELETRLE-------KLLKLCNGMVDSGKTYVNANSLFVNSLNDLSDYF--RDDSLVQNCLNKFIQALQEMN 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  130 TLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYETKFTKIEKEKREhaKQHGMirTEITGAEIAEemek 209
Cdd:cd07603   75 NFHTILLDQAQRTVSTQLQNFVKEDIKKVK-ESKKHFEKISDDLDNALVKNAQAPRS--KPQEA--EEATNILTAT---- 145
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464  210 eRRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYI 265
Cdd:cd07603  146 -RSCFRHTALDYVLQINVLQAKKRHEILSTLLSYMHAQFTFFHQGYDLLEDLEPYM 200
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
1089-1142 2.96e-11

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: 62.05  E-value: 2.96e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFV 1142
Cdd:cd11840    1 QVIALFPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNGQ---TGLFPSNYV 51
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
342-426 6.50e-11

Pleckstrin homology (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: 275388  Cd Length: 92  Bit Score: 61.79  E-value: 6.50e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  342 KKGFLLKKSDGIRKVWQRRKCAVKNGILTISHATSNRQPAKLNLL----TCQVKPNAEDKK--SFDLI-SHNRTYHFQAE 414
Cdd:cd00821    1 KEGYLLKRGGGGLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIplsgILEVEEVSPKERphCFELVtPDGRTYYLQAD 80
                         90
                 ....*....|..
gi 65301464  415 DEQDYIAWISVL 426
Cdd:cd00821   81 SEEERQEWLKAL 92
Ank_2 pfam12796
Ankyrin repeats (3 copies);
620-692 1.62e-10

Ankyrin repeats (3 copies);


Pssm-ID: 315466  Cd Length: 92  Bit Score: 60.51  E-value: 1.62e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 65301464    620 LHLAVRtadQTSLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYGKPECLKLLLrSKPTVDIVNQNGETALDIA 692
Cdd:pfam12796    1 LHLAAK---NGDLELVKLLLEEGADANLQDKNGRTALHLAAKNGHLEIVKLLL-EHADVNLKDKNGRTALHYA 69
PLN03131 PLN03131
hypothetical protein; Provisional
445-568 2.10e-10

hypothetical protein; Provisional


Pssm-ID: 178677  Cd Length: 705  Bit Score: 64.80  E-value: 2.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   445 GENSLEDLTKAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMgvhISRIQSLELDKLGTSELLLAKN 524
Cdd:PLN03131    2 GSRKEEERNEKIIRGLMKLPPNRRCINCNSLGPQFVCTNFWTFICMTCSGIHREF---THRVKSVSMSKFTSQDVEALQN 78
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 65301464   525 VGNNSFNDIMEANLPSPSPKPTPSSDMTVRKEYITAKYVDHRFS 568
Cdd:PLN03131   79 GGNQRAREIYLKDWDQQRQRLPDNSKVDKIREFIKDIYVDKKYA 122
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
1089-1144 4.07e-10

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


Pssm-ID: 212808  Cd Length: 55  Bit Score: 58.52  E-value: 4.07e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEE--DQEWWIGHIEGqpeRKGVFPVSFVHI 1144
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSKDceDKGWWKGELNG---KRGVFPDNFVEP 55
BAR_ACAP1 cd07639
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
54-264 5.00e-10

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 1), also called centaurin beta-1, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP1 also participates in the cargo sorting and recycling of the transferrin receptor and integrin beta1. It may also play a role in innate immune responses. ACAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153323  Cd Length: 200  Bit Score: 60.70  E-value: 5.00e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSnfLSRDNPDLGTAFVKFS-TLTKELSTLL 132
Cdd:cd07639    1 RAAIEEVEAEVSELETRLEKLVKLGSGMLEGGRHYCAASRAFVDGLCDLAH--HGPKDPMMAECLEKFSdGLNHILDSHA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  133 KnLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYETKFTKIEKEKREHAKQhgmirteitGAEIAEEMEKERR 212
Cdd:cd07639   79 E-LLEATQFSFKQQLQLLVKEDLRGFR-DARKEFERGAESLEAALQHNAETPRRKAQE---------VEEAAAALLGARA 147
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 65301464  213 LFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQY 264
Cdd:cd07639  148 TFRDRALDYALQINVIEDKKKFDILEFMLQLMEAQASFFQQGHEALSALHQY 199
SH3_STAM cd11820
Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as ...
1088-1142 5.89e-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: 58.25  E-value: 5.89e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1088 RRVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWighiEGQPERK-GVFPVSFV 1142
Cdd:cd11820    1 RKVRALYDFEAAEDNELTFKAGEIITVLDDSDPNWW----KGSNHRGeGLFPANFV 52
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
614-672 8.89e-10

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 58.93  E-value: 8.89e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 65301464  614 ELGETALHLAVRTADqtsLHLVDFLVQNCGNLDKQTSVGNTVLHYCSMYGKPECLKLLL 672
Cdd:cd00204   71 KDGNTPLHLAARNGN---LDVVKLLLKHGADVNARDKDGRTPLHLAAKNGHLEVVKLLL 126
SH3_STAM2 cd11963
Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST ...
1088-1142 1.62e-09

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: 56.95  E-value: 1.62e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1088 RRVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWighiEGQPERK-GVFPVSFV 1142
Cdd:cd11963    2 RKVRALYDFEAVEDNELTFKHGEIIIVLDDSDANWW----KGENHRGvGLFPSNFV 53
SH3_STAM1 cd11964
Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal ...
1088-1142 2.05e-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: 56.50  E-value: 2.05e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1088 RRVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHiegQPERKGVFPVSFV 1142
Cdd:cd11964    1 RKVRAIYDFEAAEDNELTFKAGDIITILDDSDPNWWKGE---TPQGTGLFPSNFV 52
PH pfam00169
PH domain; PH stands for pleckstrin homology.
341-426 2.90e-09

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 306640  Cd Length: 105  Bit Score: 57.19  E-value: 2.90e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    341 EKKGFLLKKSDGIRKVWQRRKCAVKNGILTI----SHATSNRQPAKLNLLTCQVK-----PNAEDKKSFDLI----SHNR 407
Cdd:pfam00169    2 VKEGWLLKKGGGKKKSWKKRYFVLFDGSLLYykddKSGKSKEPKGSISLSGCEVVevvapDSPKRKFCFELRtgerTGGR 81
                           90
                   ....*....|....*....
gi 65301464    408 TYHFQAEDEQDYIAWISVL 426
Cdd:pfam00169   82 TYLLQAESEEERKDWIKAI 100
BAR_APPL cd07601
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
107-254 2.97e-09

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains, and are localized to cytoplasmic membranes. Vertebrates contain two APPL proteins, APPL1 and APPL2. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153285  Cd Length: 215  Bit Score: 58.38  E-value: 2.97e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  107 LSRDNPDLGTAFVKFSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYE---TKFTKIEKe 183
Cdd:cd07601   56 LGRDDEILVSTLKQFSKVVDELSTMHSTLSSQLADTVLHPISQFMESDLAEIM-TLKELFKAASNDHDgvlSKYSRLSK- 133
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 65301464  184 KREHAKQHgmirteitgAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDG 254
Cdd:cd07601  134 KRENTKVK---------IEVNDEVYACRKKQHQTAMNYYCALNLLQYKKTTALLEPMIGYLQAQIAFFKMG 195
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
1090-1142 3.77e-09

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: 3.77e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11961    2 AKALYDYDAAEDNELSFFENDKIINIEFVDDDWWLGECHG---SRGLFPSNYV 51
BAR_ACAP3 cd07637
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
57-265 4.50e-09

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3), also called centaurin beta-5, is presumed to be an Arf GTPase activating protein (GAP) based on its similarity to the Arf6-specific GAPs ACAP1 and ACAP2. The specific function of ACAP3 is still unknown. ACAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153321  Cd Length: 200  Bit Score: 57.70  E-value: 4.50e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   57 VTLLEEALDQDRTALQKVKKSVKAIYNSGQdHVQNEENYAQVLDKFGSNFlsrdnpdlgtafvkfstltKELSTLLKNLL 136
Cdd:cd07637   22 VKLCSGMIEAGKAYATTNKLFVSGIRDLSQ-QCKKDEMISECLDKFGDSL-------------------QEMVNYHMILF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  137 QGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYETKFTKIEKEKREhaKQHGMirTEITGAeiaeeMEKERRLFQL 216
Cdd:cd07637   82 DQAQRSVRQQLHSFVKEDVRKFK-ETKKQFDKVREDLEIALVKNAQAPRH--KPHEV--EEATST-----LTITRKCFRH 151
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 65301464  217 QMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYI 265
Cdd:cd07637  152 LALDYVLQINVLQAKKKFEILDSMLSFMHAQYTFFQQGYSLLHELDPYM 200
PLN03119 PLN03119
putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional
445-581 6.29e-09

putative ADP-ribosylation factor GTPase-activating protein AGD14; Provisional


Pssm-ID: 178666  Cd Length: 648  Bit Score: 59.86  E-value: 6.29e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   445 GENSLEDLTKAIIEDVQRLPGNDICCDCGSSEPTWLSTNLGILTCIECSGIHREMgvhISRIQSLELDKLGTSELLLAKN 524
Cdd:PLN03119    2 GSKREEERNEKIIRGLMKLPPNRRCINCNSLGPQYVCTTFWTFVCMACSGIHREF---THRVKSVSMSKFTSKEVEVLQN 78
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464   525 VGNNSFNDIMEANLPSPSPKPTPSSDMTVRKEYITAKYVDHRFSRKTCASSSAKLNE 581
Cdd:PLN03119   79 GGNQRAREIYLKNWDHQRQRLPENSNAERVREFIKNVYVQKKYAGANDADKPSKDSQ 135
SH3_Endophilin_A cd11803
Src homology 3 domain of Endophilin-A; Endophilins play roles in synaptic vesicle formation, ...
1091-1145 6.47e-09

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: 54.96  E-value: 6.47e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1091 KTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHIL 1145
Cdd:cd11803    4 RALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQ---SGFFPVNYVEVL 55
SH3_9 pfam14604
Variant SH3 domain;
1093-1142 9.80e-09

Variant SH3 domain;


Pssm-ID: 291278  Cd Length: 50  Bit Score: 54.53  E-value: 9.80e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 65301464   1093 IYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQpeRKGVFPVSFV 1142
Cdd:pfam14604    2 LYPYEPRDDDELSLRRGDVITVLEESEDGWLLGSNTTG--RTGLVPANYV 49
Ank_2 pfam12796
Ankyrin repeats (3 copies);
597-682 1.01e-08

Ankyrin repeats (3 copies);


Pssm-ID: 315466  Cd Length: 92  Bit Score: 55.50  E-value: 1.01e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    597 VYAEGVELMEPLLEPGQEL------GETALHLAVRTadqTSLHLVDFLVQNCgNLDKQTSVGNTVLHYCSMYGKPECLKL 670
Cdd:pfam12796    5 AKNGDLELVKLLLEEGADAnlqdknGRTALHLAAKN---GHLEIVKLLLEHA-DVNLKDKNGRTALHYAARSGHLEIVKL 80
                           90
                   ....*....|..
gi 65301464    671 LLRSKPTVDIVN 682
Cdd:pfam12796   81 LLEKGADINVKD 92
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
1089-1142 1.11e-08

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: 54.25  E-value: 1.11e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11826    1 KVVALYDYTADKDDELSFQEGDIIYVTKKNDDGWYEGVLNG---VTGLFPGNYV 51
BAR_APPL2 cd07632
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
90-260 1.18e-08

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. Both APPL proteins interact with the transcriptional repressor Reptin, acting as activators of beta-catenin/TCF-mediated trancription. APPL2 is essential for cell proliferation. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153316  Cd Length: 215  Bit Score: 56.57  E-value: 1.18e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   90 QNEENYA------QVLDKFGSNF-LSRDNPDLGTAFVKFSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDL 162
Cdd:cd07632   32 QNEMCLAtqqlskQLLAYEKQNFaLGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVS-TL 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  163 KKPFDKAWKDYE---TKFTKIEKeKREHAKqhgmirteiTGAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQN 239
Cdd:cd07632  111 KDLFGIASNEHDlsmAKYSRLPK-KRENEK---------VKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEP 180
                        170       180
                 ....*....|....*....|.
gi 65301464  240 LIKYYHAQCNFFQDGLKTADK 260
Cdd:cd07632  181 MLGYTHGQINFFKKGAELFSK 201
SH3_Bbc1 cd11887
Src Homology 3 domain of Bbc1 and similar domains; This subfamily is composed of Saccharomyces ...
1089-1142 1.18e-08

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


Pssm-ID: 212820  Cd Length: 60  Bit Score: 54.27  E-value: 1.18e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGH-IEGQPERK-GVFPVSFV 1142
Cdd:cd11887    3 KVKALYPYESDHEDDLNFDVGQLITVTEEEDADWYFGEyVDSNGNTKeGIFPKNFV 58
SH3_FCHSD_2 cd11762
Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of ...
1090-1138 1.20e-08

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: 54.33  E-value: 1.20e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQE----WWIGHIEGqpeRKGVFP 1138
Cdd:cd11762    2 VRALYDYEAQSDEELSFPEGAIIRILRKDDNGvddgWWEGEFNG---RVGVFP 51
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
1090-1144 1.27e-08

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: 54.24  E-value: 1.27e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFVHI 1144
Cdd:cd11877    2 VRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNG---KTGWFPSNYVKE 53
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
1089-1144 1.60e-08

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: 53.86  E-value: 1.60e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGhiEGQPERKGVFPVSFVHI 1144
Cdd:cd11819    1 RAKALYDYQAAEDNEISFVEGDIITQIEQIDEGWWLG--VNAKGQKGLFPANYVEL 54
BAR_APPL1 cd07631
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
107-272 2.34e-08

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. APPL1 interacts with diverse receptors (e.g. NGF receptor TrkA, FSHR, adiponectin receptors) and signaling proteins (e.g. Akt, PI3K), and may function as an adaptor linked to many distinct signaling pathways. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153315  Cd Length: 215  Bit Score: 55.48  E-value: 2.34e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  107 LSRDNPDLGTAFVKFSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYE---TKFTKIEKe 183
Cdd:cd07631   56 LGGDDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEIL-TLKEVFQIASNDHDaaiNRYSRLSK- 133
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  184 KREHAKqhgmirteiTGAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGlktADKLKQ 263
Cdd:cd07631  134 RRENEK---------VKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMG---SENLNE 201

                 ....*....
gi 65301464  264 YIEKLAADL 272
Cdd:cd07631  202 QLEEFLTNI 210
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
1089-1142 3.24e-08

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: 53.12  E-value: 3.24e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFV 1142
Cdd:cd11823    1 RCKALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGK---KGIFPATYV 51
SH3_Intersectin1_5 cd11995
Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
1089-1144 3.54e-08

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: 53.03  E-value: 3.54e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 1144
Cdd:cd11995    2 QVIGMYDYTAQNDDELAFSKGQIINVLNKEDPDWWKGELNGQ---VGLFPSNYVKL 54
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
1091-1139 4.29e-08

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


Pssm-ID: 278447  Cd Length: 47  Bit Score: 52.57  E-value: 4.29e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 65301464   1091 KTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPErkGVFPV 1139
Cdd:pfam00018    1 VALYDYTAREPDELSFKKGDVIIVLEKSDDGWWKGRLKGGGE--GLIPS 47
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1091-1145 4.72e-08

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


Pssm-ID: 212990  Cd Length: 56  Bit Score: 52.59  E-value: 4.72e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464 1091 KTIYDCQADNDDELTFIEGEVIIVTGEE--DQEWWIGHIEGqpeRKGVFPVSFVHIL 1145
Cdd:cd12057    3 KVLFPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNG---RRGVFPDNFVKLL 56
SH3_DNMBP_N3 cd11796
Third N-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba; DNMBP or ...
1089-1142 4.95e-08

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: 52.36  E-value: 4.95e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11796    1 QARVLQDLSAQLDEELDLREGDVVTITGILDKGWFRGELNG---RRGIFPEGFV 51
SH3_Amphiphysin cd11790
Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in ...
1089-1141 5.09e-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: 52.72  E-value: 5.09e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVT---GEEDQE--WWIGHIEGQPERkGVFPVSF 1141
Cdd:cd11790    4 KVRATHDYTAEDTDELTFEKGDVILVIpfdDPEEQDegWLMGVKESTGCR-GVFPENF 60
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
509-726 5.26e-08

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 223738  Cd Length: 235  Bit Score: 54.83  E-value: 5.26e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  509 LELDKLGTSELLLAKNVGNNSFNDIMEANLPSPSPKPTPSSDMTVRKEYITAKYVDhrfsRKTCASSSAKLNELLEAIKS 588
Cdd:COG0666    8 LLLINKCFLDLLLVALLLLLSLDLSNPSDKKLNLYLELALLPAASLSELLLKLIVD----RHLAARDLDGRLPLHSAASK 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  589 RDLLALIQVYAEGVELmepllEPGQELGETALHLAVRTADQTSLH--LVDFLVQN---CGNLDKQTSVGNTVLHYCSMYG 663
Cdd:COG0666   84 GDDKIVKLLLASGADV-----NAKDADGDTPLHLAALNGNPPEGNieVAKLLLEAgadLDVNNLRDEDGNTPLHWAALNG 158
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 65301464  664 KPECLKLLLRSKPTVDIVNQNGETALDIAKRLKATQCEDLLSQAKSG----KFNPHVHVEYEWNLRQ 726
Cdd:COG0666  159 DADIVELLLEAGADPNSRNSYGVTALDPAAKNGRIELVKLLLDKGLHlsllKFNLEGVANANVSKRN 225
BAR_GRAF2 cd07635
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR ...
71-264 6.23e-08

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. 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 which 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 also interacts with PKNbeta, which is a target of Rho. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153319  Cd Length: 207  Bit Score: 54.23  E-value: 6.23e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   71 LQKVKKSVKAIYNSGQDHVQNEEN-------YAQVLDKFGSNFLSRDNPD----LGTAFVKFSTLTKELSTLLKNLLQGL 139
Cdd:cd07635   11 LERTNRFIKELLKDGKNLIAATKSlsaaqrkFAHSLRDFKFEFIGDAETDdercIDASLQEFSNFLKNLEEQREIMALNV 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  140 SHNVIFTLDSLLKGDLKGVKgDLKKPFDKawkDYETKFTKIEKEKREHAKqhgmiRTEITGAEIAEEMEKERRLFQLQMC 219
Cdd:cd07635   91 TETLIKPLERFRKEQLGAVK-EEKKKFDK---ETEKNYSLLEKHLNLSAK-----KKEPQLQEADVQVEQNRQHFYELSL 161
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 65301464  220 EYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQY 264
Cdd:cd07635  162 EYVCKLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDFNHY 206
SH3_GRAP2_C cd11950
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2; GRAP2 is also called GADS ...
1090-1142 6.86e-08

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


Pssm-ID: 212883  Cd Length: 53  Bit Score: 52.14  E-value: 6.86e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11950    2 VRALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHG---KLGLFPANYV 51
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
342-428 9.16e-08

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. 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: 270110  Cd Length: 106  Bit Score: 52.63  E-value: 9.16e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  342 KKGFLLKKSDGiRKVWQR-----RKCAV---KNGILTISHATSNRQpaklNLLTCQVKPNAEDKKSFDLISHNRTYHFQA 413
Cdd:cd13298    8 KSGYLLKRSRK-TKNWKKrwvvlRPCQLsyyKDEKEYKLRRVINLS----ELLAVAPLKDKKRKNVFGIYTPSKNLHFRA 82
                         90
                 ....*....|....*
gi 65301464  414 EDEQDYIAWISVLTN 428
Cdd:cd13298   83 TSEKDANEWVEALRE 97
ANK cd00204
ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse ...
646-692 1.14e-07

ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other types of domains. The structural repeat unit contains two antiparallel helices and a beta-hairpin, repeats are stacked in a superhelical arrangement; this alignment contains 4 consecutive repeats.


Pssm-ID: 238125  Cd Length: 126  Bit Score: 52.77  E-value: 1.14e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 65301464  646 DKQTSVGNTVLHYCSMYGKPECLKLLLRSKPTVDIVNQNGETALDIA 692
Cdd:cd00204    1 NARDEDGRTPLHLAASNGHLEVVKLLLENGADVNAKDNDGRTPLHLA 47
PHA03247 PHA03247
large tegument protein UL36; Provisional
740-1078 1.35e-07

large tegument protein UL36; Provisional


Pssm-ID: 223021  Cd Length: 3151  Bit Score: 56.10  E-value: 1.35e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   740 PSPIKKERSPRPQSFchSSSISPQDKLALPGFSTPRDKQR---LSYGAFTNQIFASTSTDLPTSPTSEAPPLPPrnagKG 816
Cdd:PHA03247 2674 AQASSPPQRPRRRAA--RPTVGSLTSLADPPPPPPTPEPAphaLVSATPLPPGPAAARQASPALPAAPAPPAVP----AG 2747
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   817 PTGPPSTLPLGT-QTSSGSSTLSKKRPPPPppGHKRTLSDPPSPLPHGPPNKGAIPWGNDVGPLSSSKTANKFEGLSQQA 895
Cdd:PHA03247 2748 PATPGGPARPARpPTTAGPPAPAPPAAPAA--GPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPA 2825
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   896 STSSAKTALGPRVLPKLPQKVAlrktetsHHLSLDRTNIPPETF------QKSSQLTELPQKPPLGELP----PKPVELA 965
Cdd:PHA03247 2826 GPLPPPTSAQPTAPPPPPGPPP-------PSLPLGGSVAPGGDVrrrppsRSPAAKPAAPARPPVRRLArpavSRSTESF 2898
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   966 PKPQVGELPPKPGELPPKPQLGDLPPKPQLSDLPPKPQMK-DLPPKPQLGdllaksqagdvSAKVQPPSEVTQRSHTGDL 1044
Cdd:PHA03247 2899 ALPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRpQPPLAPTTD-----------PAGAGEPSGAVPQPWLGAL 2967
                         330       340       350
                  ....*....|....*....|....*....|....
gi 65301464  1045 SPnvqSRDAIQKQASEDSNDLTPTlPETPVPLPR 1078
Cdd:PHA03247 2968 VP---GRVAVPRFRVPQPAPSREA-PASSTPPLT 2997
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
341-434 1.42e-07

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. 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: 270098  Cd Length: 105  Bit Score: 51.88  E-value: 1.42e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  341 EKKGFLL---KKSDGIRKVWQRRKCAVKNGILTISHATSNR----QPAKLNLLTCQVK--PNAEDKKSFDL-ISHNRTYH 410
Cdd:cd13280    1 EKSGWLYmktSVGKPNRTIWVRRWCFVKNGVFGMLSLSPSKtyveETDKFGVLLCSVRyaPEEDRRFCFEVkIFKDISII 80
                         90       100
                 ....*....|....*....|....
gi 65301464  411 FQAEDEQDYIAWISVLTNSKEEAL 434
Cdd:cd13280   81 LQAETLKELKSWLTVFENAKRYAL 104
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
1089-1142 1.71e-07

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: 50.88  E-value: 1.71e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11827    1 QCKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRG---KEGLFPGNYV 51
SH3_Sorbs_2 cd11782
Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
1094-1144 1.88e-07

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: 50.81  E-value: 1.88e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 65301464 1094 YDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIegqPERKGVFPVSFVHI 1144
Cdd:cd11782    6 YNFNADTGVELSFRKGDVITLTRRVDENWYEGRI---GGRQGIFPVSYVQV 53
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
740-1082 2.09e-07

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteristic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 308660  Cd Length: 938  Bit Score: 55.10  E-value: 2.09e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    740 PSPIKKERS--------PRPQSFCHSSSISPQDKLALP---GFSTPRDKQRLSYGAFTNQIFASTSTDLPTSPTSEAPPL 808
Cdd:pfam03154  155 PSPMQANESdsdssappPPPGPGTQVQQPAPTPATPLPsqtPPPMTSQPQPLPVASPSTITTATSTTTTSRVVSPVDPNP 234
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    809 ------PPRNAGKGPTGPPSTLPlgtQTSSGSSTLSkkrppppppghkrtlsdppsplphgPPNKGAIPWGNDVGPLSSS 882
Cdd:pfam03154  235 dppsiiAPQSAQRGPEGPPTPQP---HSLQGPPSFP-------------------------GPAQGPGQGQGQSPPPPSL 286
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    883 KTANKFEGLSQQASTSSAKTALGPRVLPKLPQKVA----LRKTET-----SH----HLSLD-----RTNIPPETFQKSsq 944
Cdd:pfam03154  287 YPPHPNQLQSHPPSQGPHPTHSFPPKPVPLPPPPAsapqIKPPPTtpipsSHkhppHLSASpfpqmPSNLPPPPALKP-- 364
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    945 LTELPQKPPLGELPPkPVELAPKPQvgELPPKPGELPPKPQLGDLPPKPQLSDLPP-----KPQMKDLPPKPQLGDLLAK 1019
Cdd:pfam03154  365 LASLPSQHPPCAQPP-PLQLMPQPH--QLQPPPAQPPVLTQSQSHQVKGHHASPPPttaasHPSLSSTAPFPLSSASSVP 441
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 65301464   1020 SQAGDVSAKV------QPPSEVTQRSHTgdLSPNVQSRDaiQKQASEDSNDLTPTLPETPVPLPRKINT 1082
Cdd:pfam03154  442 GAVGPVPSPVpamsgpQPSSSSALSVST--VPPQLTIKE--EPLDEEEECESPPPPRRSPSPEPTIVNI 506
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
1094-1142 2.86e-07

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: 50.28  E-value: 2.86e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 65301464 1094 YDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd12052    6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKG---RRGLFPDNFV 51
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
1089-1144 3.32e-07

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: 50.02  E-value: 3.32e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 1144
Cdd:cd11874    1 RCKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGK---VGVFPSNFVKE 53
SH3_Intersectin2_5 cd11996
Fifth Src homology 3 domain (or SH3E) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1089-1144 3.34e-07

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: 49.98  E-value: 3.34e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 1144
Cdd:cd11996    2 QVIAMYDYTANNEDELSFSKGQLINVLNKDDPDWWQGEINGV---TGLFPSNYVKM 54
BAR_GAP10-like cd07634
The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are ...
62-264 3.91e-07

The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This group is composed of uncharacterized proteins called Rho GTPase activating protein (GAP) 10-like. GAP10-like may be a GAP with activity towards RhoA and Cdc42. Similar to GRAF and GRAF2, it contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of the related proteins GRAF and OPHN1, directly interact with their Rho GAP domains and inhibit theiractivity. The autoinhibited proteins are capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153318  Cd Length: 207  Bit Score: 51.95  E-value: 3.91e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   62 EALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNFL-----------SRDNPDLGTAFVKFSTLTKELST 130
Cdd:cd07634    2 ERLQCHEIELERTNKFIKELIKDGSLLIGALRNLSMAVQKFSQSLQdfqfecigdaeTDDEISIAQSLKEFARLLIAVEE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  131 LLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYetkFTKIEKEKREHAKqhgmiRTEITGAEIAEEMEKE 210
Cdd:cd07634   82 ERRRLIQNANDVLIAPLEKFRKEQIGAAK-DGKKKFDKESEKY---YSILEKHLNLSAK-----KKESHLQRADTQIDRE 152
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464  211 RRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQY 264
Cdd:cd07634  153 HQNFYEASLEYVFKIQEVQEKKKFEFVEPLLAFLQGLFTFYHEGYELAQEFAPY 206
SH3_GRB2_like_C cd11805
C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related ...
1089-1142 4.35e-07

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: 49.55  E-value: 4.35e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11805    1 RVQALYDFNPQEPGELEFRRGDIITVLDSSDPDWWKGELRG---RVGIFPANYV 51
BAR_ACAP2 cd07638
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
54-265 4.80e-07

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2), also called centaurin beta-2, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153322  Cd Length: 200  Bit Score: 51.54  E-value: 4.80e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFgSNFLSRDNPdLGTAFVKFSTLTKELSTLLK 133
Cdd:cd07638    1 RAALEDVEGDVAELELKLDKLVKLCIGMIDAGKAFCQANKQFMNGIRDL-AQYSSKDAV-IETSLTKFSDTLQEMINYHT 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  134 NLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYETKFTKIEKEKREhaKQHGMirteitgAEIAEEMEKERRL 213
Cdd:cd07638   79 ILFDQAQRSIKAQLQTFVKEDLRKFK-DAKKQFDKVSEEKENALVKNAQVQRN--KQHEV-------EEATNILTATRKC 148
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 65301464  214 FQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADKLKQYI 265
Cdd:cd07638  149 FRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLTFFHQGYDLFSELGPYM 200
Drf_FH1 pfam06346
Formin Homology Region 1; This region is found in some of the Diaphanous related formins (Drfs) ...
932-1014 5.48e-07

Formin Homology Region 1; This region is found in some of the Diaphanous related formins (Drfs). It consists of low complexity repeats of around 12 residues.


Pssm-ID: 283903  Cd Length: 152  Bit Score: 50.67  E-value: 5.48e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    932 TNIPPETFQKSSqlTELPQKPPL----GELPPKPvelaPKPQVGELPPKPGELPPKPQLGDLPPKPQLSDLPPKPQMKDL 1007
Cdd:pfam06346   62 TSIPPPPPLPGS--TGIPPPPPLpggaGIPPPPP----PLPGGAGIPPPPPPLPGGPGIPPPPPFPGGPGIPPPPPGMGM 135

                   ....*..
gi 65301464   1008 PPKPQLG 1014
Cdd:pfam06346  136 PPPPPFG 142
BAR_OPHN1 cd07633
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid ...
54-246 6.61e-07

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Oligophrenin-1 (OPHN1) is a GTPase activating protein (GAP) with activity towards RhoA, Rac, and Cdc42, that is expressed in developing spinal cord and in adult brain areas with high plasticity. It plays a role in regulating the actin cystoskeleton as well as morphology changes in axons and dendrites, and may also function in modulating neuronal connectivity. Mutations in the OPHN1 gene causes X-linked mental retardation associated with cerebellar hypoplasia, lateral ventricle enlargement and epilepsy. OPHN1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153317  Cd Length: 207  Bit Score: 51.16  E-value: 6.61e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   54 RNTVTLLEEALDQDRTALQKVKKSVKAIYNSGQDHVQNEENYAQVLDKFGSNF----LSRDNPDLGTAFVKFSTLTKELS 129
Cdd:cd07633    1 RERLKCYEQELERTNKFIKDVIKDGNALISAIKEYSSAVQKFSQTLQSFQFDFigdtLTDDEINIAESFKEFAELLQEVE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  130 TLLKNLLQGLSHNVIFTLDSLLKGDLkGVKGDLKKPFDKawkDYETKFTKIEKEKREHAKqhgmiRTEITGAEIAEEMEK 209
Cdd:cd07633   81 EERMMMVQNASDLLIKPLENFRKEQI-GFTKERKKKFEK---DSEKFYSLLDRHVNLSSK-----KKESQLQEADLQVDK 151
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 65301464  210 ERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHA 246
Cdd:cd07633  152 ERQNFYESSLEYVYQIQEVQESKKFDVVEPVLAFLHS 188
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
342-429 8.16e-07

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. 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: 270108  Cd Length: 103  Bit Score: 49.77  E-value: 8.16e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  342 KKGFLLKKSDGI----RKVWQRRKCAVKNGILTI--SHATSNRQPAKLNLLTCQVK-PNAEDKKSFDLISHNRTYHFQAE 414
Cdd:cd13296    1 KSGWLTKKGGGSstlsRRNWKSRWFVLRDTVLKYyeNDQEGEKLLGTIDIRSAKEIvDNDPKENRLSITTEERTYHLVAE 80
                         90
                 ....*....|....*
gi 65301464  415 DEQDYIAWISVLTNS 429
Cdd:cd13296   81 SPEDASQWVNVLTRV 95
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
342-428 1.16e-06

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. 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: 241436  Cd Length: 96  Bit Score: 49.22  E-value: 1.16e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  342 KKGFLLKKSdGIRKVWQRRKCAVKNGILTI---SHATSNRQPAKLNLLT-CQVKPnAEDKKSFDLISHNRTYHFQAEDEQ 417
Cdd:cd13282    1 KAGYLTKLG-GKVKTWKRRWFVLKNGELFYyksPNDVIRKPQGQIALDGsCEIAR-AEGAQTFEIVTEKRTYYLTADSEN 78
                         90
                 ....*....|.
gi 65301464  418 DYIAWISVLTN 428
Cdd:cd13282   79 DLDEWIRVIQN 89
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
1089-1142 1.19e-06

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


Pssm-ID: 311542  Cd Length: 54  Bit Score: 48.24  E-value: 1.19e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 65301464   1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:pfam07653    1 YGRAIFDYVGTDPTELSLKKGDVIKVLDKDSDGWWEGENGG---RKGLVPSSAV 51
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
1090-1142 1.47e-06

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: 48.10  E-value: 1.47e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQpeRKGVFPVSFV 1142
Cdd:cd11825    2 VKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGK--KQKWFPANYV 52
Cytadhesin_P30 pfam07271
Cytadhesin P30/P32; This family consists of several Mycoplasma species specific Cytadhesin P32 ...
934-1009 1.49e-06

Cytadhesin P30/P32; This family consists of several Mycoplasma species specific Cytadhesin P32 and P30 proteins. P30 has been found to be membrane associated and localized on the tip organelle. It is thought that it is important in cytadherence and virulence.


Pssm-ID: 284643  Cd Length: 308  Bit Score: 51.39  E-value: 1.49e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    934 IPPETFQKSSQL-------TELPQKPPLGELPPKPVELAPKPQVGELPPKPGELPP-----KPQLGDLPpkPQLSDLPPK 1001
Cdd:pfam07271  157 NNPQMGINQPQIninfgpnPQQRINPQCFGFPMQPGQMAMRPGFNQMPPHMGGAPPnqmgmRPGFNQMP--PQMGGMAPR 234

                   ....*...
gi 65301464   1002 PQMKDLPP 1009
Cdd:pfam07271  235 PGFPNHMP 242
SH3_Eve1_3 cd11816
Third Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
1089-1142 1.54e-06

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: 48.17  E-value: 1.54e-06
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11816    1 RCVARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNG---KIGIFPLNFV 51
SH3_Intersectin2_3 cd11992
Third Src homology 3 domain (or SH3C) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
1093-1142 1.75e-06

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: 48.08  E-value: 1.75e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 65301464 1093 IYDCQADNDDELTFIEGEVIIVTgEEDQEWWIGHIEgqpERKGVFPVSFV 1142
Cdd:cd11992    5 LYPYSSSEPGDLTFNEGEEILVT-QKDGEWWTGSIE---DRTGIFPSNYV 50
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
1090-1142 1.76e-06

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  Cd Length: 53  Bit Score: 48.03  E-value: 1.76e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11873    2 VIVEFDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNG---KRGMFPDNFV 51
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
1089-1142 2.08e-06

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: 47.67  E-value: 2.08e-06
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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQE-WWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11882    1 RARALYACKAEDESELSFEPGQIITNVQPSDEPgWLEGTLNG---RTGLIPENYV 52
SH3_OSTF1 cd11772
Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or ...
1090-1142 2.49e-06

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: 47.29  E-value: 2.49e-06
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                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11772    2 FRALYDYEAQHPDELSFEEGDLLYISDKSDPNWWKATCGG---KTGLIPSNYV 51
Pro-rich pfam15240
Proline-rich; This family includes several eukaryotic proline-rich proteins.
933-1012 2.58e-06

Proline-rich; This family includes several eukaryotic proline-rich proteins.


Pssm-ID: 291893  Cd Length: 160  Bit Score: 48.45  E-value: 2.58e-06
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gi 65301464    933 NIPPEtfQKSSQLTELPQKPPLGELPPKPVELAP--KPQvgELPPKPG--ELPPKPQLGDLPPKPQLSDLPPKPQMKDL- 1007
Cdd:pfam15240   31 VISDE--GSSQQGGNQPQGPPPGGFPPQPPGPPPqgGPQ--QPPPQGGnpQGPPPQGGPQRPPGPGNQQGPPPQGGNQQq 106

                   ....*....
gi 65301464   1008 ----PPKPQ 1012
Cdd:pfam15240  107 rpppPGKPQ 115
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
1090-1142 2.74e-06

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: 47.37  E-value: 2.74e-06
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                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd12061    2 VRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNG---RTGWFPSNYV 51
SH3_Eve1_4 cd11817
Fourth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
1093-1141 3.17e-06

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: 47.09  E-value: 3.17e-06
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                 ....*....|....*....|....*....|....*....|....*....
gi 65301464 1093 IYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSF 1141
Cdd:cd11817    5 LYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNG---REGIFPRAF 50
GGN pfam15685
Gametogenetin; GGN is a family of proteins largely found in mammals. It reacts with POG in the ...
935-1089 3.18e-06

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: 317988  Cd Length: 648  Bit Score: 51.20  E-value: 3.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464    935 PPETFQKSSqlTELPQKPPLGELPPkPVELAPKPQVGEL----PPKPGELPPKPqlgdlPPKPqlsdlPPKPQMKDLPPK 1010
Cdd:pfam15685  392 PPPPGQKHP--APGPRRPAPALLAP-PMFIFPAPTNGEPvrpgPPGQQELPPMP-----PPVP-----PPTPQPPALQPT 458
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   1011 PQLGDLLAKSQAGDVSAKVQPPSevtqrshTGDLSPNVQsrdAIQKQASEDSNDLTP----TLPETPVPLPRKINTGKNK 1086
Cdd:pfam15685  459 PLPVAPPPTPGPGHAESALAPPP-------APALPPALA---ADQTPAPAPAPSPAPapttAEPLPPAPAPTKTRTRRNK 528

                   ...
gi 65301464   1087 VRR 1089
Cdd:pfam15685  529 GSR 531
SH3_CD2AP_3 cd12056
Third Src Homology 3 domain (SH3C) of CD2-associated protein; CD2AP, also called CMS (Cas ...
1091-1144 3.55e-06

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: 47.13  E-value: 3.55e-06
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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1091 KTIYDCQADNDDELTFIEGEVIIVTGEE--DQEWWIGHIEGqpeRKGVFPVSFVHI 1144
Cdd:cd12056    5 KALFHYEGTNEDELDFKEGEIILIISKDtgEPGWWKGELNG---KEGVFPDNFVSQ 57
SH3_Intersectin_3 cd11838
Third Src homology 3 domain (or SH3C) of Intersectin; Intersectins (ITSNs) are adaptor ...
1094-1142 3.73e-06

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: 47.02  E-value: 3.73e-06
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gi 65301464 1094 YDCQADNDDELTFIEGEVIIVTgEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11838    6 YPYESNEPGDLTFNAGDVILVT-KKDGEWWTGTIGD---RTGIFPSNYV 50
SH3_SNX9_like cd11763
Src Homology 3 domain of Sorting Nexin 9 and similar proteins; Sorting nexins (SNXs) are Phox ...
1089-1144 3.76e-06

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: 46.94  E-value: 3.76e-06
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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWighIEGQPER--KGVFPVSFVHI 1144
Cdd:cd11763    1 KVRALYDFDSQPSGELSLRAGEVLTITRQDVGDGW---LEGRNSRgeVGLFPSSYVEI 55
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
1089-1142 4.18e-06

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: 47.01  E-value: 4.18e-06
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                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHieGQPERKGVFPVSFV 1142
Cdd:cd11960    1 RARALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGT--GPDGTYGLFPANYV 52
SH3_Sorbs2_2 cd11923
Second Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
1094-1145 4.71e-06

Second 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: 212856  Cd Length: 57  Bit Score: 46.83  E-value: 4.71e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 65301464 1094 YDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQpERKGVFPVSFVHIL 1145
Cdd:cd11923    7 YNFNADTNVELSLRKGDRVVLLKQVDQNWYEGKIPGT-NRQGIFPVSYVEVI 57
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
1091-1142 5.36e-06

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: 46.69  E-value: 5.36e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1091 KTIYDCQADNDDELTFIEGEVIIVTGE--EDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd12142    3 RVLFDYNPVAPDELALKKGDVIEVISKetEDEGWWEGELNG---RRGFFPDNFV 53
SH3_PACSIN cd11843
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) ...
1089-1142 5.92e-06

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: 46.26  E-value: 5.92e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWI-GHIEGqpeRKGVFPVSFV 1142
Cdd:cd11843    1 PVRALYDYEGQESDELSFKAGDILTKLEEEDEQGWCkGRLDG---RVGLYPANYV 52
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
1089-1142 9.11e-06

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: 45.96  E-value: 9.11e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHI-EGQperKGVFPVSFV 1142
Cdd:cd11812    1 TVVALYDYTANRSDELTIHRGDIIRVLYKDNDNWWFGSLvNGQ---QGYFPANYV 52
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
1093-1145 1.00e-05

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: 45.59  E-value: 1.00e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1093 IYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFVHIL 1145
Cdd:cd12073    6 LYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHG---HRGLFPANYVELL 55
SH3_p67phox_C cd12046
C-terminal (or second) Src Homology 3 domain of the p67phox subunit of NADPH oxidase; p67phox, ...
1090-1142 1.34e-05

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: 45.18  E-value: 1.34e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWighiEGQPERK-GVFPVSFV 1142
Cdd:cd12046    2 VVALFSYEASQPEDLEFQKGDVILVLSKVNEDWL----EGQCKGKiGIFPSAFV 51
SH3_PACSIN3 cd11997
Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons 3 (PACSIN3); ...
1089-1142 1.37e-05

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


Pssm-ID: 212930  Cd Length: 56  Bit Score: 45.34  E-value: 1.37e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWI-GHIegQPERKGVFPVSFV 1142
Cdd:cd11997    3 RVRALYDYTGQEADELSFKAGEELLKIGEEDEQGWCkGRL--LSGRIGLYPANYV 55
SH3_Bzz1_2 cd11778
Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP ...
1090-1141 1.51e-05

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: 45.18  E-value: 1.51e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVI-IVTGEEDQEWWIGHIEGQperKGVFPVSF 1141
Cdd:cd11778    2 VEALYDYEAQGDDEISIRVGDRIaVIRGDDGSGWTYGEINGV---KGLFPTSY 51
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
1089-1142 1.72e-05

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: 45.05  E-value: 1.72e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTgEEDQEWWIGHIEGQpeRKGVFPVSFV 1142
Cdd:cd11837    1 TATALYPWRAKKENHLSFAKGDIITVL-EQQEMWWFGELEGG--EEGWFPKSYV 51
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
1090-1142 1.79e-05

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: 44.99  E-value: 1.79e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd12060    4 VKARFNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNG---KTGWFPSNYV 53
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
1088-1142 2.08e-05

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: 44.96  E-value: 2.08e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1088 RRVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd12054    1 RQCKVLFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLNG---KSGLFPSNFV 52
SH3_MLK cd11876
Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), ...
1093-1142 2.19e-05

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: 44.81  E-value: 2.19e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 65301464 1093 IYDCQADNDDELTFIEGEVIIVTGEE-----DQEWWIGHIegqPERKGVFPVSFV 1142
Cdd:cd11876    5 LFDYDARGEDELTLRRGQPVEVLSKDaavsgDEGWWTGKI---GDKVGIFPSNYV 56
SH3_GRAP_C cd11951
C-terminal Src homology 3 domain of GRB2-related adaptor protein; GRAP is a GRB-2 like adaptor ...
1090-1143 2.64e-05

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


Pssm-ID: 212884  Cd Length: 53  Bit Score: 44.41  E-value: 2.64e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1090 VKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFVH 1143
Cdd:cd11951    2 VQAQYDFSAEDPSQLSFRRGDIIEVLDCPDPNWWRGRISG---RVGFFPRNYVH 52
SH3_Eve1_5 cd11818
Fifth Src homology 3 domain of ADAM-binding protein Eve-1; Eve-1, also called SH3 ...
1089-1141 2.79e-05

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


Pssm-ID: 212752  Cd Length: 50  Bit Score: 44.40  E-value: 2.79e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSF 1141
Cdd:cd11818    1 KARALYDFTGENEDELSFKAGDIITELESIDEEWMSGELRG---KSGIFPKNF 50
SH3_SNX18 cd11897
Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal ...
1089-1144 3.02e-05

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR 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: 212830  Cd Length: 55  Bit Score: 44.21  E-value: 3.02e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQPERkGVFPVSFVHI 1144
Cdd:cd11897    1 RARALYDFRSENPGEISLREHEVLSLCSEQDIEGWLEGVNSRGDR-GLFPASYVEV 55
SH3_Sorbs2_1 cd11920
First Src Homology 3 domain of Sorbin and SH3 domain containing 2 (Sorbs2), also called ...
1091-1142 3.24e-05

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: 44.23  E-value: 3.24e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 65301464 1091 KTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFV 1142
Cdd:cd11920    4 RAVYDFKAQTSKELSFKKGDTVYILRKIDQNWYEGEHHG---RVGIFPISYV 52
SH3_Sorbs_1 cd11781
First Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar ...
1091-1144 3.32e-05

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: 44.25  E-value: 3.32e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1091 KTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFVHI 1144
Cdd:cd11781    3 RALYPFKAQSAKELSLKKGDIIYIRRQIDKNWYEGEHNG---RVGIFPASYVEI 53
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
341-432 3.36e-05

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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: 270073  Cd Length: 94  Bit Score: 44.69  E-value: 3.36e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464  341 EKKGFLLKKS-DGIRKVWQRRkcAVKNGILTISHATSNRQPAKLNL--LTC-QVKPNAEDKKsFDLISHNRTYHFQAEDE 416
Cdd:cd13253    1 IKSGYLDKQGgQGNNKGFQKR--WVVFDGLSLRYFDSEKDAYSKRIipLSAiSTVRAVGDNK-FELVTTNRTFVFRAESD 77
                         90
                 ....*....|....*.
gi 65301464  417 QDYIAWISVLTNSKEE 432
Cdd:cd13253   78 DERNLWCSTLQAAISE 93
PHA03247 PHA03247
large tegument protein UL36; Provisional
740-1016 3.69e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021  Cd Length: 3151  Bit Score: 48.01  E-value: 3.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   740 PSPIKKERSPRPQSFCHSSSISPQDKLALPGfSTPRDKQRLSYGAFTNQIfastsTDLPTSPTSEAPP------------ 807
Cdd:PHA03247 2647 PPPERPRDDPAPGRVSRPRRARRLGRAAQAS-SPPQRPRRRAARPTVGSL-----TSLADPPPPPPTPepaphalvsatp 2720
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   808 LPPRNAGKGPTGPPSTL-------PLGTQTSSGSSTLSKKRPPPP----------PPGHKRTLSDPPSPLPHGPPNKGAI 870
Cdd:PHA03247 2721 LPPGPAAARQASPALPAapappavPAGPATPGGPARPARPPTTAGppapappaapAAGPPRRLTRPAVASLSESRESLPS 2800
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   871 PWGNDVGPLSSSKTANKFEGLSQQAS-----TSSAKTA-------------LGPRVLP------KLPQKVALRKTETSHH 926
Cdd:PHA03247 2801 PWDPADPPAAVLAPAAALPPAASPAGplpppTSAQPTApppppgppppslpLGGSVAPggdvrrRPPSRSPAAKPAAPAR 2880
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   927 LSLDRTNIPPETFQKSS--QLTELPQKPPLGELPPKPVELAPKPQvgelPPKPGELPPKPQLGDLPPKPQlSDLPPKPQM 1004
Cdd:PHA03247 2881 PPVRRLARPAVSRSTESfaLPPDQPERPPQPQAPPPPQPQPQPPP----PPQPQPPPPPPPRPQPPLAPT-TDPAGAGEP 2955
                         330
                  ....*....|..
gi 65301464  1005 KDLPPKPQLGDL 1016
Cdd:PHA03247 2956 SGAVPQPWLGAL 2967
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
1089-1144 3.83e-05

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


Pssm-ID: 212895  Cd Length: 54  Bit Score: 44.02  E-value: 3.83e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGhIEGQPERkGVFPVSFVHI 1144
Cdd:cd11962    1 RAVVLYDYEKDEDNEIELVEGEIVTNIEMVDEDWWMG-TNSKGES-GLFPSNYVEL 54
SH3_Sla1p_3 cd11775
Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates ...
1088-1144 4.10e-05

Third Src Homology 3 domain of the fungal endocytic adaptor protein Sla1p; Sla1p facilitates endocytosis by playing a role as an adaptor protein in coupling components of the actin cytoskeleton to the endocytic machinery. It interacts with Abp1p, Las17p and Pan1p, which are activator proteins of actin-related protein 2/3 (Arp2/3). Sla1p contains multiple domains including three SH3 domains, a SAM (sterile alpha motif) domain, and a Sla1 homology domain 1 (SHD1), which binds to the NPFXD motif that is found in many integral membrane proteins such as the Golgi-localized Arf-binding protein Lsb5p and the P4-ATPases, Drs2p and Dnf1p. The third SH3 domain of Sla1p can bind ubiquitin while retaining the ability to bind proline-rich ligands; monoubiquitination of target proteins signals internalization and sorting through the endocytic pathway. 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: 212709  Cd Length: 57  Bit Score: 43.85  E-value: 4.10e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 65301464 1088 RRVKTIYDCQADNDDELTFIEG-EVIIVTGEEDQEWWIGHIEGQpERKGVFPVSFVHI 1144
Cdd:cd11775    1 KRGKVLYDFDAQSDDELTVKEGdVVYILDDKKSKDWWMVENVST-GKEGVVPASYIEI 57
SH3_Abi1 cd11971
Src homology 3 domain of Abl Interactor 1; Abi1, also called e3B1, is a central regulator of ...
1089-1142 4.71e-05

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: 43.86  E-value: 4.71e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFV 1142
Cdd:cd11971    1 KVVAIYDYSKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNGV---TGLFPGNYV 51
SH3_SGSM3 cd11813
Src Homology 3 domain of Small G protein Signaling Modulator 3; SGSM3 is also called ...
1089-1144 5.35e-05

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: 43.64  E-value: 5.35e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 65301464 1089 RVKTIYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGQperKGVFPVSFVHI 1144
Cdd:cd11813    1 RAKALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNGL---RGWFPAKFVEL 53
SH3_ARHGEF9_like cd11828
Src homology 3 domain of ARHGEF9-like Rho guanine nucleotide exchange factors; Members of this ...
1093-1144 5.60e-05

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: 43.52  E-value: 5.60e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 65301464 1093 IYDCQADNDDELTFIEGEVIIVTGEEDQEWWIGHIEGqpeRKGVFPVSFVHI 1144
Cdd:cd11828    5 LWDHVTMDPEELGFKAGDVIEVLDMSDKDWWWGSIRD---EEGWFPASFVRL 53
Ank_4 pfam13637
Ankyrin repeats (many copies);
652-692 5.89e-05

Ankyrin repeats (many copies);


Pssm-ID: 316185  Cd Length: 54  Bit Score: 43.43  E-value: 5.89e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 65301464    652 GNTVLHYCSMYGKPECLKLLLRSKPTVDIVNQNGETALDIA 692
Cdd:pfam13637    1 ELTALHAAAASGHLELLRLLLENGADINAVDGNGETALHFA 41
PHA03247 PHA03247
large tegument protein UL36; Provisional
742-1078 6.83e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021  Cd Length: 3151  Bit Score: 47.24  E-value: 6.83e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   742 PIKKERSPRPQSFCHSSSISPQdklALPGFSTPRdkqRLSYGAFTNQIFASTSTDLPTSPTSEAPPLPPRNAGKGPTGPP 821
Cdd:PHA03247 2751 PGGPARPARPPTTAGPPAPAPP---AAPAAGPPR---RLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASP 2824
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 65301464   822 STL--PLGTQTSSGSSTLSKKRPPPPPPGhkrtlsdppsplphgppnkGAIPW