The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-A; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Endophilins are accessory proteins, localized at synapses, which interact with the endocytic proteins, dynamin and synaptojanin. They are essential for synaptic vesicle formation from the plasma membrane. They interact with voltage-gated calcium channels, thus linking vesicle endocytosis to calcium regulation. They also play roles in virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. 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. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms. 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. The BAR domains of endophilin-A1 and A3 form crescent-shaped dimers that can detect membrane curvature and drive membrane bending.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944   1 MEKKVDVTSKAVTEVLARTIEYLQPNPASRAKLTMLNTVSKIRGQVKNPGYPQSEGLLGECMIRHGKELGGESNFGDALL 80
Cdd:cd07592    12 MERKTDATSKLVEDLIPKTKEYLQPNPAARAKLAMQNTYSKIRGQAKSTKYPQPEGLLGEVMLKYGRELGEDSNFGQALV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  81 DAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFEESKE 160
Cdd:cd07592    92 EVGEALKQLAEVKDSLDDNVKQNFLDPLQQLQDKDLKEINHHRKKLEGRRLDYDYKKRKQGKGPDEELKQAEEKFEESKE 171

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462566944 161 VAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKLKRRMREA 212
Cdd:cd07592   172 LAENSMFNLLENDVEQVSQLSALVEAQLDYHRQSAEILEELQSKLQERISEA 223

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-A; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Endophilins are accessory proteins, localized at synapses, which interact with the endocytic proteins, dynamin and synaptojanin. They are essential for synaptic vesicle formation from the plasma membrane. They interact with voltage-gated calcium channels, thus linking vesicle endocytosis to calcium regulation. They also play roles in virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. 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. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms. 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. The BAR domains of endophilin-A1 and A3 form crescent-shaped dimers that can detect membrane curvature and drive membrane bending.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944   1 MEKKVDVTSKAVTEVLARTIEYLQPNPASRAKLTMLNTVSKIRGQVKNPGYPQSEGLLGECMIRHGKELGGESNFGDALL 80
Cdd:cd07592    12 MERKTDATSKLVEDLIPKTKEYLQPNPAARAKLAMQNTYSKIRGQAKSTKYPQPEGLLGEVMLKYGRELGEDSNFGQALV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  81 DAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFEESKE 160
Cdd:cd07592    92 EVGEALKQLAEVKDSLDDNVKQNFLDPLQQLQDKDLKEINHHRKKLEGRRLDYDYKKRKQGKGPDEELKQAEEKFEESKE 171

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462566944 161 VAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKLKRRMREA 212
Cdd:cd07592   172 LAENSMFNLLENDVEQVSQLSALVEAQLDYHRQSAEILEELQSKLQERISEA 223

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944    1 MEKKVDVTSKAVTEVLARTIEYLQPNPASRAKLTMLNTVSKIRGQVKNPGypqsegllgecmiRHGKELGGESNFGDALL 80
Cdd:smart00721  32 LERRFDTTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGG-------------DDGEGLGADSSYGKALD 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944   81 DAGESMKRLAEVKDSLdIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKK------KRQGKIPD--------E 146
Cdd:smart00721  99 KLGEALKKLLQVEESL-SQVKRTFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARhklkkaKKSKEKKKdeklakaeE 177

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462566944  147 ELRQALEKFEESKEVAETSMHNLLETDIE-QVSQLSALVDAQLDYHRQAVQILDELAEKLKR 207
Cdd:smart00721 178 ELRKAKQEFEESNAQLVEELPQLVASRVDfFVNCLQALIEAQLNFHRESYKLLQQLQQQLDK 239

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462566944  272 DQPSCKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGML-DGQSGFFPLSYVE 326
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLgRGKEGLFPSNYVE 56

phosphodiesterase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  84 ESMKRLAEVKDSLDIEVKQNFIDpLQNLCEKDLKEIQHHLKKLEGR----------RLDFDYKKKRQGKIPDEELRQALE 153
Cdd:PRK12704   46 EAKKEAEAIKKEALLEAKEEIHK-LRNEFEKELRERRNELQKLEKRllqkeenldrKLELLEKREEELEKKEKELEQKQQ 124

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462566944 154 KFEESKEVAETsMHNLLETDIEQVSQLSAlvdaqlDYHRQavQILDELAEKLKrrmREASSRPKR 218
Cdd:PRK12704  125 ELEKKEEELEE-LIEEQLQELERISGLTA------EEAKE--ILLEKVEEEAR---HEAAVLIKE 177

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-A; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Endophilins are accessory proteins, localized at synapses, which interact with the endocytic proteins, dynamin and synaptojanin. They are essential for synaptic vesicle formation from the plasma membrane. They interact with voltage-gated calcium channels, thus linking vesicle endocytosis to calcium regulation. They also play roles in virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. 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. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms. 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. The BAR domains of endophilin-A1 and A3 form crescent-shaped dimers that can detect membrane curvature and drive membrane bending.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944   1 MEKKVDVTSKAVTEVLARTIEYLQPNPASRAKLTMLNTVSKIRGQVKNPGYPQSEGLLGECMIRHGKELGGESNFGDALL 80
Cdd:cd07592    12 MERKTDATSKLVEDLIPKTKEYLQPNPAARAKLAMQNTYSKIRGQAKSTKYPQPEGLLGEVMLKYGRELGEDSNFGQALV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  81 DAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFEESKE 160
Cdd:cd07592    92 EVGEALKQLAEVKDSLDDNVKQNFLDPLQQLQDKDLKEINHHRKKLEGRRLDYDYKKRKQGKGPDEELKQAEEKFEESKE 171

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462566944 161 VAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKLKRRMREA 212
Cdd:cd07592   172 LAENSMFNLLENDVEQVSQLSALVEAQLDYHRQSAEILEELQSKLQERISEA 223

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-A1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. 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. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms. Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. Endophilin-A1 (or endophilin-1) is also referred to as SH3P4 (SH3 domain containing protein 4) or SH3GL2 (SH3 domain containing Grb2-like protein 2). It is localized in presynaptic nerve terminals. It plays many roles in clathrin-dependent endocytosis of synaptic vesicles including early vesicle formation, ubiquitin-dependent sorting of plasma membrane proteins, and regulation of calcium influx into neurons. The BAR domain of endophilin-A1 forms crescent-shaped dimers that can detect membrane curvature and drive membrane bending, while its SH3 domain binds the endocytic proteins, dynamin 1, synaptojanin 1, and amphiphysins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944   1 MEKKVDVTSKAVTEVLARTIEYLQPNPASRAKLTMLNTVSKIRGQVKNPGYPQSEGLLGECMIRHGKELGGESNFGDALL 80
Cdd:cd07613    12 MERKVDVTSRAVMEIMTKTIEYLQPNPASRAKLSMINTMSKIRGQEKGPGYPQAEALLAEAMLKFGRELGDECNFGPALG 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  81 DAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFEESKE 160
Cdd:cd07613    92 DVGEAMRELSEVKDSLDMEVKQNFIDPLQNLHDKDLREIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFDESKE 171

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462566944 161 VAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKLKRRMREA 212
Cdd:cd07613   172 IAESSMFNLLEMDIEQVSQLSALVQAQLEYHKQATQILQQVTVKLEDRIREA 223

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944   1 MEKKVDVTSKAVTEVLARTIEYLQPNPASRAKLTMLNtvskirgqvknpgypQSEGLLGECMIRHGKELGGESNFGDALL 80
Cdd:pfam03114  31 LERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTVLE---------------QPEELLAESMIEAGKDLGEDSSFGKALE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  81 DAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCeKDLKEIQHHLKKLEGRRLDFDYKKKRQGKIP-------------DEE 147
Cdd:pfam03114  96 DYGEALKRLAQLLEQLDDRVETNFLDPLRNLL-KEFKEIQKHRKKLERKRLDYDAAKTRVKKAKkkksskakdesqaEEE 174

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462566944 148 LRQALEKFEESKEVAETSMHNLLETDIEQV-SQLSALVDAQLDYHRQAVQILDELAEKL 205
Cdd:pfam03114 175 LRKAQAKFEESNEQLKALLPNLLSLEVEFVvNQLVAFVEAQLDFHRQCYQLLEQLQQQL 233

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462566944 274 PSCKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEVL 328
Cdd:cd11803     1 PCCRALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMVNGQSGFFPVNYVEVL 55

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-B; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. 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. They are classified into two types, A and B. Vertebrates contain two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  13 TEVLARTIE-YLQPNPASRAKltmlNTVSKIRGQVKNPGYPQSEgLLGECMIRHGKELGGESNFGDALLDAGESMKRLAE 91
Cdd:cd07594    33 TEKILKQTEaVLQPNPNVRVE----DFIYEKLDRKKPDRLSNLE-QLGQAMIEAGNDFGPGTAYGSALIKVGQAQKKLGQ 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  92 VKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKKKRQGKI--------PDEELRQALEKFEESKEVAE 163
Cdd:cd07594   108 AEREFIQTSSSNFLQPLRNFLEGDMKTISKERKLLENKRLDLDACKTRVKKAksaeaieqAEQDLRVAQSEFDRQAEITK 187

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 2462566944 164 TSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKL 205
Cdd:cd07594   188 LLLEGISSTHANHLRCLRDFVEAQMTYYAQCYQYMDDLQRQL 229

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-B1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. 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. They are classified into two types, A and B. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. Endophilin-B1, also called Bax-interacting factor 1 (Bif-1) or SH3GLB1 (SH3-domain GRB2-like endophilin B1), is localized mainly to the Golgi apparatus. It is involved in the regulation of many biological events including autophagy, tumorigenesis, nerve growth factor (NGF) trafficking, neurite outgrowth, mitochondrial outer membrane dynamics, and cell death. Endophilin-B1 forms homo- and heterodimers (with endophilin-B2) through its BAR domain, which can bind and bend membranes. It interacts with amphiphysin 1 and dynamin 1 through its SH3 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944   4 KVDVTSKAVTEVLARTIEYLQPNPASRAKLTMLNTVSKirgqvKNPGYPQSEGLLGECMIRHGKELGGESNFGDALLDAG 83
Cdd:cd07616    25 KAECTKHWTEKIMKQTEVLLQPNPNARIEEFVYEKLDR-----KAPSRMNNPELLGQYMIDAGNEFGPGTAYGNALIKCG 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  84 ESMKRLAEVKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDFDYKKKRQGK--------IPDEELRQALEKF 155
Cdd:cd07616   100 ETQKQIGTADRELIQTSAINFLTPLRNFIEGDYKTITKERKLLQNKRLDLDAAKTRLKKakvaearaAAEQELRITQSEF 179

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462566944 156 EESKEVAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKL 205
Cdd:cd07616   180 DRQAEITRLLLEGISSTHAHHLRCLNDFVEAQMTYYAQCYQYMLDLQKQL 229

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEV 327
Cdd:cd11786     3 KALYNYEGKEPGDLSFKKGDIILLRKRIDENWYHGECNGKQGFFPASYVQV 53

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462566944 276 CKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGML-DGQSGFFPLSY 324
Cdd:cd00174     2 ARALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELnGGREGLFPANY 51

The Bin/Amphiphysin/Rvs (BAR) domain of Rich-like Rho GTPase Activating Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of Rho and Rac GTPase activating proteins (GAPs) with similarity to GAP interacting with CIP4 homologs proteins (Rich). Members contain an N-terminal BAR domain, followed by a Rho GAP domain, and a C-terminal prolin-rich region. Vertebrates harbor at least three Rho GAPs in this subfamily including Rich1, Rich2, and SH3-domain binding protein 1 (SH3BP1). Rich1 and Rich2 play complementary roles in the establishment and maintenance of cell polarity. Rich1 is a Cdc42- and Rac-specific GAP that binds to polarity proteins through the scaffold protein angiomotin and plays a role in maintaining the integrity of tight junctions. Rich2 is a Rac GAP that interacts with CD317 and plays a role in actin cytoskeleton organization and the maintenance of microvilli in polarized epithelial cells. SH3BP1 is a Rac GAP that inhibits Rac-mediated platelet-derived growth factor (PDGF)-induced membrane ruffling. 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 Rich1 has been shown to form oligomers, bind membranes and induce membrane tubulation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944  54 SEGLLGECMIRHGKELGGESNFGDALLDAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCEKDLKEIQHHLKKLEGRRLDF 133
Cdd:cd07595    58 PEYGLAQSMLESSKELPDDSLLGKVLKLCGEAQNTLARELVDHEMNVEEDVLSPLQNILEVEIPNIQKQKKRLSKLVLDM 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462566944 134 DYKKKR-------------QGKIP--DEELRQALEKFEESKEVAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQIL 198
Cdd:cd07595   138 DSARSRynaahkssggqgaAAKVDalKDEYEEAELKLEQCRDALATDMYEFLAKEAEIASYLIDLIEAQREYHRTALSVL 217

                         170
                  ....*....|....*...
gi 2462566944 199 DELAEKLKRRMREASSRP 216
Cdd:cd07595   218 EAVLPELQEQIEQSPSKP 235

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEV 327
Cdd:cd11782     3 RAKYNFNADTGVELSFRKGDVITLTRRVDENWYEGRIGGRQGIFPVSYVQV 53

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.

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gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVE 326
Cdd:cd11877     3 RAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTGWFPSNYVK 52

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.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462566944 275 SCKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEV 327
Cdd:cd11823     1 RCKALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGIFPATYVEE 53

First Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the first SH3 domain, located at the N-terminal half, of SH3RF3. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462566944 274 PSCKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVE 326
Cdd:cd11928     1 PCGKALYSYEGKEPGDLKFNKGDIIILRRKVDENWYHGELNGCHGFLPASYIQ 53

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

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462566944 276 CKALYDFEP-ENDGE--LGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSY 324
Cdd:cd11787     2 CKALYDFEMkDEDEKdcLTFKKGDVITVIRRVDENWAEGRLGDKIGIFPISF 53

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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 2462566944 276 CKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYV 325
Cdd:cd11816     2 CVARFDFEGEQEDELSFSEGDVITLKEYVGEEWAKGELNGKIGIFPLNFV 51

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGML-DGQSGFFPLSYVE 326
Cdd:cd11960     3 RALYDYQAADDTEISFDPGDIITDIEQIDEGWWRGTGpDGTYGLFPANYVE 53

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

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gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLD-GQSGFFP 321
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKgGKEGLIP 46

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462566944 276 CKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEV 327
Cdd:cd11874     2 CKVLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNGKVGVFPSNFVKE 53

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.

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gi 2462566944 276 CKALYDFEPENDGELGFHEGDVITLTNQ--IDENWYEGMLDGQSGFFPLSYVEV 327
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKdcEDKGWWKGELNGKRGVFPDNFVEP 55

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

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gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEVL 328
Cdd:cd11919     4 RAKFDFKAQTLKELPLQKGDIVYIYKQIDQNWYEGEHHGRVGIFPRSYIELL 55

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462566944 276 CKALYDFEPENDGELGFHEGDVITLT----NQIDENWYEGMLDGQSGFFPLSYVE 326
Cdd:cd11762     2 VRALYDYEAQSDEELSFPEGAIIRILrkddNGVDDGWWEGEFNGRVGVFPSLVVE 56

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462566944 276 CKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVE 326
Cdd:cd11827     2 CKALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTGRLRGKEGLFPGNYVE 52

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEV 327
Cdd:cd11813     3 KALLDFERHDDDELGFRKNDIITIISQKDEHCWVGELNGLRGWFPAKFVEL 53

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

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gi 2462566944 275 SCKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEV 327
Cdd:cd11959     1 TAVALYDYQAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYGLFPANYVEL 53

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.

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gi 2462566944 276 CKALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSY 324
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVTEHLDAEWSRGRLNGREGIFPRAF 50

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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVE 326
Cdd:cd11950     3 RALYDFEALEDDELGFNSGDVIEVLDSSNPSWWKGRLHGKLGLFPANYVA 52

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462566944 278 ALYDFEPENDGELGFHEGDVITLTNQIDENWYEGMLDGQSGFFPLSYVEVL 328
Cdd:cd12073     5 ALYDYQGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRGLFPANYVELL 55

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.

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gi 2462566944 277 KALYDFEPENDGELGFHEGDVITLTNQIDE-NWYEGMLDGQSGFFPLSYVE 326
Cdd:cd11882     3 RALYACKAEDESELSFEPGQIITNVQPSDEpGWLEGTLNGRTGLIPENYVE 53