Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain GRB2-like endophilin B2), is a cytoplasmic protein that interacts with the apoptosis inducer Bax. It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They 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. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain. The related protein endophilin-B1 interacts with amphiphysin 1 and dynamin 1 through its 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 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11944     1 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNQKGKVPVTYLEL 55

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040   16 FTRAVQFTEEKFGQAEKTELDAHFENLLARADSTKNWTEKILRQTEVLLQPNPSARVEEFLYEKLDRKVPSRVTNGella 95
Cdd:smart00721   6 FNRAKQKVGEKVGKAEKTKLDEDFEELERRFDTTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGG---- 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040   96 qymaDAASELGPTTPYGKTLIKVAEAEKQLGAAERDFIHTASiSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKAR 175
Cdd:smart00721  82 ----DDGEGLGADSSYGKALDKLGEALKKLLQVEESLSQVKR-TFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHK 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040  176 LKKAKAAEAKATlwNDEVDKAEQELRVAQTEFDR-QAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQ 254
Cdd:smart00721 157 LKKAKKSKEKKK--DEKLAKAEEELRKAKQEFEEsNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQ 234

                   ....*
gi 1622869040  255 KQLGR 259
Cdd:smart00721 235 QQLDK 239

Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain GRB2-like endophilin B2), is a cytoplasmic protein that interacts with the apoptosis inducer Bax. It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They 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. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain. The related protein endophilin-B1 interacts with amphiphysin 1 and dynamin 1 through its 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 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11944     1 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNQKGKVPVTYLEL 55

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 1622869040  317 RKARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGN-KKGKVPVTYLE 371
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVLE--KSDDGWWKGRLGRgKEGLFPSNYVE 56

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 1622869040  21 QFTEEKFGQAEKTELDAHFENLLARADSTKNWTEKILRQTEVLLQPNPSARVEEFLYEKLDRKVPSRVTNGELLAQYMAD 100
Cdd:cd07594     1 QFTEEKLGTAEKTEYDAHFENLLQRADKTKVWTEKILKQTEAVLQPNPNVRVEDFIYEKLDRKKPDRLSNLEQLGQAMIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040 101 AASELGPTTPYGKTLIKVAEAEKQLGAAERDFIHTASISFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAK 180
Cdd:cd07594    81 AGNDFGPGTAYGSALIKVGQAQKKLGQAEREFIQTSSSNFLQPLRNFLEGDMKTISKERKLLENKRLDLDACKTRVKKAK 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622869040 181 AAeakatlwnDEVDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 257
Cdd:cd07594   161 SA--------EAIEQAEQDLRVAQSEFDRQAEITKLLLEGISSTHANHLRCLRDFVEAQMTYYAQCYQYMDDLQRQL 229

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040   16 FTRAVQFTEEKFGQAEKTELDAHFENLLARADSTKNWTEKILRQTEVLLQPNPSARVEEFLYEKLDRKVPSRVTNGella 95
Cdd:smart00721   6 FNRAKQKVGEKVGKAEKTKLDEDFEELERRFDTTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGG---- 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040   96 qymaDAASELGPTTPYGKTLIKVAEAEKQLGAAERDFIHTASiSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKAR 175
Cdd:smart00721  82 ----DDGEGLGADSSYGKALDKLGEALKKLLQVEESLSQVKR-TFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHK 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040  176 LKKAKAAEAKATlwNDEVDKAEQELRVAQTEFDR-QAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQ 254
Cdd:smart00721 157 LKKAKKSKEKKK--DEKLAKAEEELRKAKQEFEEsNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQ 234

                   ....*
gi 1622869040  255 KQLGR 259
Cdd:smart00721 235 QQLDK 239

Src homology 3 domain of Endophilin-B2; Endophilin-B2, also called SH3GLB2 (SH3-domain GRB2-like endophilin B2), is a cytoplasmic protein that interacts with the apoptosis inducer Bax. It is overexpressed in prostate cancer metastasis and has been identified as a cancer antigen with potential utility in immunotherapy. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. They 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. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain. The related protein endophilin-B1 interacts with amphiphysin 1 and dynamin 1 through its 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 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11944     1 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNQKGKVPVTYLEL 55

Src homology 3 domain of Endophilin-B; 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 two endophilin-B isoforms. Endophilin-B proteins are cytoplasmic proteins expressed mainly in the heart, placenta, and skeletal muscle. 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 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTY 369
Cdd:cd11802     1 KARVLYDYDAEDSTELSLLADEVITVYELPGMDEDYMMGERGSQRGKVPVAY 52

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 1622869040  31 EKTELDAHFENLLARADSTKNWTEKILRQTEVLLQPNPSARVEEFLYEKLDR-----KVPSRVTNGELLAQYMADAASEL 105
Cdd:cd07613     1 EGTKLDDDFKEMERKVDVTSRAVMEIMTKTIEYLQPNPASRAKLSMINTMSKirgqeKGPGYPQAEALLAEAMLKFGREL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040 106 GPTTPYGKTLIKVAEAEKQLGAAERDFIHTASISFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAkaaeak 185
Cdd:cd07613    81 GDECNFGPALGDVGEAMRELSEVKDSLDMEVKQNFIDPLQNLHDKDLREIQHHLKKLEGRRLDFDYKKKRQGKI------ 154

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040 186 atlwndevdkAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQ 245
Cdd:cd07613   155 ----------PDEELRQALEKFDESKEIAESSMFNLLEMDIEQVSQLSALVQAQLEYHKQ 204

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040  45 RADSTKNWTEKILRQTEVLLQpnpsarveeflyekldrKVPSRVTNGELLAQYMADAASELGP--TTPYGKTLIKVAEAE 122
Cdd:cd07307     1 KLDELEKLLKKLIKDTKKLLD-----------------SLKELPAAAEKLSEALQELGKELPDlsNTDLGEALEKFGKIQ 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040 123 KQLGAAERDFIHTASISFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAKAAEAKAtlwnDEVDKAEQELRV 202
Cdd:cd07307    64 KELEEFRDQLEQKLENKVIEPLKEYLKKDLKEIKKRRKKLDKARLDYDAAREKLKKLRKKKKDS----SKLAEAEEELQE 139

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622869040 203 AQTEFDrqaEVTRLLLEGISSTHVNHLR----CLHEFVKSQTTYYAQCYRHMLDLQKQ 256
Cdd:cd07307   140 AKEKYE---ELREELIEDLNKLEEKRKElflsLLLSFIEAQSEFFKEVLKILEQLLPY 194

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-A3; 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 that interacts 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. Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. Endophilin-A3 (or endophilin-3) is also referred to as SH3P13 (SH3 domain containing protein 13) or SH3GL3 (SH3 domain containing Grb2-like protein 3). It regulates Arp2/3-dependent actin filament assembly during endocytosis. It binds N-WASP through its SH3 domain and enhances the ability of N-WASP to activate the Arp2/3 complex. Endophilin-A3 co-localizes with the vesicular glutamate transporter 1 (VGLUT1), and may play an important role in the synaptic release of glutamate.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040  31 EKTELDAHFENLLARADSTKNWTEKILRQTEVLLQPNPSARVEEFLYEKLDRKVPSRVTNGE-----LLAQYMADAASEL 105
Cdd:cd07615     1 EGTKLDDDFQEMERKIDVTNKVVAELLSKTTEYLQPNPAYRAKLGMLNTVSKIRGQVKTTGYpqtegLLGDCMLRYGREL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040 106 GPTTPYGKTLIKVAEAEKQLGAAERDFIHTASISFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAkaaeak 185
Cdd:cd07615    81 GEESTFGNALLDVGESMKQMAEVKDSLDINVKQNFIDPLQLLQDKDLKEIGHHLKKLEGRRLDFDYKKKRQGKI------ 154

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622869040 186 atlwndevdkAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 257
Cdd:cd07615   155 ----------PDEEIRQAVEKFEESKELAERSMFNFLENDVEQVSQLSVLIEAALDYHRQSTEILEDLQSKL 216

The Bin/Amphiphysin/Rvs (BAR) domain of Schizosaccharomyces pombe Meiotically Up-regulated Gene 137 protein and similar proteins; 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. This subfamily is composed predominantly of uncharacterized fungal proteins with similarity to Schizosaccharomyces pombe Meiotically Up-regulated Gene 137 protein (MUG137), which may play a role in meiosis and sporulation in fission yeast. MUG137 contains an N-terminal BAR domain and a C-terminal SH3 domain, similar to endophilins. Endophilins play roles in synaptic vesicle formation, virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040  77 YEKLDRKVP-----SRVTNGELLAQYMADAASELGPTTPYGKTLIKVAEAEKQLGAAERDFIHTASISFLTPLRNFLEgD 151
Cdd:cd07593    34 VEYLSKKKPllddkDKCLPVEALGLVMINHGEEFPQDSEYGSCLSKLGRAHCKIGTLQEEFADRLSDTFLANIERSLA-E 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622869040 152 WKTISKERRLLQNRRLDLDACKARLKKAKAaeakatlwndEVDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRC 231
Cdd:cd07593   113 MKEYHSARKKLESRRLAYDAALTKSQKAKK----------EDSRLEEELRRAKAKYEESSEDVEARMVAIKESEADQYRD 182

                         170
                  ....*....|....*
gi 1622869040 232 LHEFVKSQTTYYAQC 246
Cdd:cd07593   183 LTDLLDAELDYHQQS 197

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 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGE-RGNKKGKVPVTY 369
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGElNGGREGLFPANY 51

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1622869040 319 ARVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFV--DDDWWLGECHGSRGLFPSNYVEL 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11875     1 KARVLFDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFPDNFVEP 55

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1622869040 317 RKARVLYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNKKGKVPVTYL 370
Cdd:cd11964     1 RKVRAIYDFEAAEDNELTFKAGDIITI--LDDSDPNWWKGETPQGTGLFPSNFV 52

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.

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNKKGKVPVTYLE 371
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITV--LDSSDPDWWKGELRGRVGIFPANYVQ 52

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.

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVYSlPGMDPDWLIGErgNKKGKV---PVTYLE 371
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITR-QDVGDGWLEGR--NSRGEVglfPSSYVE 54

First 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 first 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 1622869040 318 KARVLYDYEAADSSELALLADELITVyslpgMDPD----W-LIGERGNKKGKVPVTYLEL 372
Cdd:cd11912     1 TAKVLYDYTASGDDEVSISEGEEVTV-----LEPDdgsgWtKVRNGSGEEGLVPTSYIEI 55

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.

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITvySLPGMDPDWLIGErgNKKGK---VPVTYLEL 372
Cdd:cd11962     1 RAVVLYDYEKDEDNEIELVEGEIVT--NIEMVDEDWWMGT--NSKGEsglFPSNYVEL 54

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

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLpgMDPDW-LIGERGNKKGKVPVTYL 370
Cdd:cd11774     1 QAKALYDYDKQTEEELSFNEGDTLDVYDD--SDSDWiLVGFNGTQFGFVPANYI 52

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 1622869040 320 RVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGER-GNKKGKVPV 367
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKS--EDGWWKGRNkGGKEGLIPS 47

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

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11842     1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVEL 55

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.

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11781     1 KARALYPFKAQSAKELSLKKGDIIYIRR--QIDKNWYEGEHNGRVGIFPASYVEI 53

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.

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gi 1622869040 320 RVLYDYEAADSSELALlaDELITVYSLPGMDPDWLIGERGNKKGKVPVTYLE 371
Cdd:cd11772     3 RALYDYEAQHPDELSF--EEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVE 52

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

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gi 1622869040 315 GTRKARVLYDYEAADSSELALLADEliTVYSLPGMDPDWLIG--ERGNKKGKVPVTYLE 371
Cdd:cd11934     1 GGKRYRAVYDYNAADEDEVSFQDGD--TIVNVQQIDDGWMYGtvERTGDTGMLPANYVE 57

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

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLE 371
Cdd:cd11836     1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEPGWLAGELKGKTGWFPANYVE 54

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.

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVysLPGMDPD-----WLIG--ERGNKKGKVPVTYLELL 373
Cdd:cd11790     4 KVRATHDYTAEDTDELTFEKGDVILV--IPFDDPEeqdegWLMGvkESTGCRGVFPENFTERI 64

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

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gi 1622869040 315 GTRKARvlYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLE 371
Cdd:cd11977     1 GTAVAR--YNFAARDMRELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYVE 55

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.

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gi 1622869040 318 KARVLYDYEAADSSELALLADELITVYSLpgMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11828     1 LAEALWDHVTMDPEELGFKAGDVIEVLDM--SDKDWWWGSIRDEEGWFPASFVRL 53

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 1622869040 320 RVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLE 371
Cdd:cd11823     3 KALYSYTANREDELSLQPGDIIEVHE--KQDDGWWLGELNGKKGIFPATYVE 52

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

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gi 1622869040 317 RKARVLYDYEAADSSELALLADeliTVYS--LPGMDPDWLIGERGNKKGKVPVTYLELL 373
Cdd:cd12064     1 RKAKALYACKAEHDSELSFTAG---TVFDnvHPSQEPGWLEGTLNGKTGLIPENYVEFL 56