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 576067783 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11944    1 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNQKGKVPVTYLEL 55

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783    16 FTRAVQFTEEKFGQAEKTELDAHFENLLARADSTKNWTERILRQTEVLLQPNPSARVEEFLYEKLDRKVPSRVTNGella 95
Cdd:smart00721   6 FNRAKQKVGEKVGKAEKTKLDEDFEELERRFDTTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGG---- 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783    96 qymaEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASlSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKAR 175
Cdd:smart00721  82 ----DDGEGLGADSSYGKALDKLGEALKKLLQVEESLSQVKR-TFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHK 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783   176 LKKAKAAEAKATlwNDEVDKAEQELRVAQTEFDR-QAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQ 254
Cdd:smart00721 157 LKKAKKSKEKKK--DEKLAKAEEELRKAKQEFEEsNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQ 234

                   ....*
gi 576067783   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 576067783 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 576067783   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 576067783  21 QFTEEKFGQAEKTELDAHFENLLARADSTKNWTERILRQTEVLLQPNPSARVEEFLYEKLDRKVPSRVTNGELLAQYMAE 100
Cdd:cd07594    1 QFTEEKLGTAEKTEYDAHFENLLQRADKTKVWTEKILKQTEAVLQPNPNVRVEDFIYEKLDRKKPDRLSNLEQLGQAMIE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783 101 AASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAK 180
Cdd:cd07594   81 AGNDFGPGTAYGSALIKVGQAQKKLGQAEREFIQTSSSNFLQPLRNFLEGDMKTISKERKLLENKRLDLDACKTRVKKAK 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 576067783 181 AAeakatlwnDEVDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 257
Cdd:cd07594  161 SA--------EAIEQAEQDLRVAQSEFDRQAEITKLLLEGISSTHANHLRCLRDFVEAQMTYYAQCYQYMDDLQRQL 229

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783    16 FTRAVQFTEEKFGQAEKTELDAHFENLLARADSTKNWTERILRQTEVLLQPNPSARVEEFLYEKLDRKVPSRVTNGella 95
Cdd:smart00721   6 FNRAKQKVGEKVGKAEKTKLDEDFEELERRFDTTEAEIEKLQKDTKLYLQPNPAVRAKLASQKKLSKSLGEVYEGG---- 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783    96 qymaEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASlSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKAR 175
Cdd:smart00721  82 ----DDGEGLGADSSYGKALDKLGEALKKLLQVEESLSQVKR-TFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHK 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783   176 LKKAKAAEAKATlwNDEVDKAEQELRVAQTEFDR-QAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQ 254
Cdd:smart00721 157 LKKAKKSKEKKK--DEKLAKAEEELRKAKQEFEEsNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQ 234

                   ....*
gi 576067783   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 576067783 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 576067783 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTY 369
Cdd:cd11802    1 KARVLYDYDAEDSTELSLLADEVITVYELPGMDEDYMMGERGSQRGKVPVAY 52

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-A2; 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. Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. Endophilin-A2 (or endophilin-2) is also referred to as SH3P8 (SH3 domain containing protein 8) or SH3GL1 (SH3 domain containing Grb2-like protein 1). It localizes to presynaptic nerve terminals and forms heterodimers with endophilin-A1 through their BAR domains. Endophilin-A2 binds dynamin 1, synaptojanin 1, and the beta1-adrenergic receptor cytoplasmic tail through its SH3 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783  31 EKTELDAHFENLLARADSTKNWTERILRQTEVLLQPNPSARVEEFLYEKLDR-----KVPSRVTNGELLAQYMAEAASEL 105
Cdd:cd07614    1 EGTKLDDDFKEMEKKVDLTSKAVTEVLARTIEYLQPNPASRAKLTMLNTVSKirgqvKNPGYPQSEGLLGETMIRYGKEL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783 106 GPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAkaaeak 185
Cdd:cd07614   81 GDESNFGDALLDAGESMKRLAEVKDSLDIEVKQNFIDPLQNLCDKDLKEIQHHLKKLEGRRLDFDYKKKRQGKI------ 154

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 576067783 186 atlwndevdkAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQLGR 259
Cdd:cd07614  155 ----------PDEELRQAMEKFEESKEVAETSMHNLLETDIEQVSQLSALVDAQLDYHRQAVQILDELAEKLKR 218

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 576067783  45 RADSTKNWTERILRQTEVLLQpnpsarveeflyekldrKVPSRVTNGELLAQYMAEAASELGP--STPYGKTLIKVSEAE 122
Cdd:cd07307    1 KLDELEKLLKKLIKDTKKLLD-----------------SLKELPAAAEKLSEALQELGKELPDlsNTDLGEALEKFGKIQ 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 576067783 123 KRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAKAAEAKAtlwnDEVDKAEQELRV 202
Cdd:cd07307   64 KELEEFRDQLEQKLENKVIEPLKEYLKKDLKEIKKRRKKLDKARLDYDAAREKLKKLRKKKKDS----SKLAEAEEELQE 139

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 576067783 203 AQTEFDrqaEVTRLLLEGISSTHVNHLR----CLHEFVKSQTTYYAQCYRHMLDLQKQ 256
Cdd:cd07307  140 AKEKYE---ELREELIEDLNKLEEKRKElflsLLLSFIEAQSEFFKEVLKILEQLLPY 194

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 576067783  25 EKFGQAEKTE-LDAHFENLLARADSTKNWTERILRQTEVLLQPNPSARveeflYEKLDRKVPSRVtngelLAQYMAEAAS 103
Cdd:cd07595    2 QTVGRAEKTEvLSDELLQIEKRVEAVKDACQNIHKKLISCLQGQSGED-----KDKRLKKLPEYG-----LAQSMLESSK 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 576067783 104 ELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDA 171
Cdd:cd07595   72 ELPDDSLLGKVLKLCGEAQNTLARELVDHEMNVEEDVLSPLQNILEVEIPNIQKQKKRLSKLVLDMDS 139

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 576067783   317 RKARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGN-KKGKVPVTYLE 371
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVLE--KSDDGWWKGRLGRgKEGLFPSNYVE 56

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 576067783 318 KARVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGE-RGNKKGKVPVTY 369
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGElNGGREGLFPANY 51

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 576067783 317 RKARVLYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNKKGKVPVTYL 370
Cdd:cd11964    1 RKVRAIYDFEAAEDNELTFKAGDIITI--LDDSDPNWWKGETPQGTGLFPSNFV 52

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 576067783 319 ARVLYDYEAADSSELALLADELITvySLPGMDPDWLIGE-RGNKKGKVPVTYLEL 372
Cdd:cd11819    2 AKALYDYQAAEDNEISFVEGDIIT--QIEQIDEGWWLGVnAKGQKGLFPANYVEL 54

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 576067783 318 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11875    1 KARVLFDYEAENEDELTLREGDIVTILSKDCEDKGWWKGELNGKRGVFPDNFVEP 55

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 576067783 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 576067783 318 KARVLYDYEAADSSELALLADELITVYSlPGMDPDWLIGErgNKKGKV---PVTYLE 371
Cdd:cd11763    1 KVRALYDFDSQPSGELSLRAGEVLTITR-QDVGDGWLEGR--NSRGEVglfPSSYVE 54

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 576067783 318 KARVLYDYEAADSSELALLADELIT-VYslPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11882    1 RARALYACKAEDESELSFEPGQIITnVQ--PSDEPGWLEGTLNGRTGLIPENYVEF 54

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 576067783 317 RKARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLELL 373
Cdd:cd11919    1 RPARAKFDFKAQTLKELPLQKGDIVYIYK--QIDQNWYEGEHHGRVGIFPRSYIELL 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 576067783 318 KARVLYDYEAADSSELALLADELITvySLPGMDPDWLIGErgNKKGK---VPVTYLEL 372
Cdd:cd11962    1 RAVVLYDYEKDEDNEIELVEGEIVT--NIEMVDEDWWMGT--NSKGEsglFPSNYVEL 54

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 576067783  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 576067783 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 576067783 318 KARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11781    1 KARALYPFKAQSAKELSLKKGDIIYIRR--QIDKNWYEGEHNGRVGIFPASYVEI 53

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.

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gi 576067783 319 ARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLELL 373
Cdd:cd11803    3 CRALYDFEPENEGELGFKEGDIITLTN--QIDENWYEGMVNGQSGFFPVNYVEVL 55

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 576067783 315 GTRKARVLYDYEAADSSELALLADEliTVYSLPGMDPDWLIG--ERGNKKGKVPVTYLE 371
Cdd:cd11934    1 GGKRYRAVYDYNAADEDEVSFQDGD--TIVNVQQIDDGWMYGtvERTGDTGMLPANYVE 57

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

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gi 576067783 319 ARVLYDYEAADSSELALLADEliTVYSLPGMDPDWLIGERGNKKGKVPVTYLELL 373
Cdd:cd11920    3 ARAVYDFKAQTSKELSFKKGD--TVYILRKIDQNWYEGEHHGRVGIFPISYVEKL 55

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

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gi 576067783 318 KARVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11840    1 QVIALFPYTAQNEDELSFQKGDIINVLSKD--DPDWWRGELNGQTGLFPSNYVEP 53

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 576067783 318 KARVLYDYEAADSSELALLADELITVysLPGMDPD-----WLIG--ERGNKKGKVPVTYLELL 373
Cdd:cd11790    4 KVRATHDYTAEDTDELTFEKGDVILV--IPFDDPEeqdegWLMGvkESTGCRGVFPENFTERI 64

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 576067783 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 576067783 320 RVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLE 371
Cdd:cd11823    3 KALYSYTANREDELSLQPGDIIEVHE--KQDDGWWLGELNGKKGIFPATYVE 52

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

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gi 576067783 322 LYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNKKGKVPVTYLEL 372
Cdd:cd11996    6 MYDYTANNEDELSFSKGQLINV--LNKDDPDWWQGEINGVTGLFPSNYVKM 54