Src homology 3 domain of Endophilin-B1; Endophilin-B1, also called Bax-interacting factor 1 (Bif-1) or SH3GLB1 (SH3-domain GRB2-like endophilin B1), is localized mainly to the Golgi apparatus. It is involved in the regulation of many biological events including autophagy, tumorigenesis, nerve growth factor (NGF) trafficking, neurite outgrowth, mitochondrial outer membrane dynamics, and cell death. 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-B1 forms homo- and heterodimers (with endophilin-B2) through its BAR domain. It 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578799206 342 SGSRKARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITYLELLN 402
Cdd:cd11945    1 SGSRKARVLYDYDAANSTELSLLADEVITVYSVPGMDSDWLMGERGNQKGKVPITYLELLN 61

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206   19 LSRAVQFTEEKLGQAEKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEkldrkapsriNNPELLG 98
Cdd:pfam03114   5 FNRASQLLGEKVGGAEKTKLDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTVLE----------QPEELLA 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206   99 QYMIDAGTEFGPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIeGDYKTIAKERKLLQNKRLDLDAAKTR 178
Cdd:pfam03114  75 ESMIEAGKDLGEDSSFGKALEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLL-KEFKEIQKHRKKLERKRLDYDAAKTR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206  179 LKKAKAAETRNSQLNSarlegdnimvnfsymlnflhvkwlkiwaeevtKSEQELRITQSEFDRQAEITRLLLEGISSTHA 258
Cdd:pfam03114 154 VKKAKKKKSSKAKDES--------------------------------QAEEELRKAQAKFEESNEQLKALLPNLLSLEV 201

                         250       260       270
                  ....*....|....*....|....*....|....
gi 578799206  259 HHL-RCLNDFVEAQMTYYAQCYQYMLDLQKQLGS 291
Cdd:pfam03114 202 EFVvNQLVAFVEAQLDFHRQCYQLLEQLQQQLGK 235

Src homology 3 domain of Endophilin-B1; Endophilin-B1, also called Bax-interacting factor 1 (Bif-1) or SH3GLB1 (SH3-domain GRB2-like endophilin B1), is localized mainly to the Golgi apparatus. It is involved in the regulation of many biological events including autophagy, tumorigenesis, nerve growth factor (NGF) trafficking, neurite outgrowth, mitochondrial outer membrane dynamics, and cell death. 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-B1 forms homo- and heterodimers (with endophilin-B2) through its BAR domain. It 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578799206 342 SGSRKARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITYLELLN 402
Cdd:cd11945    1 SGSRKARVLYDYDAANSTELSLLADEVITVYSVPGMDSDWLMGERGNQKGKVPITYLELLN 61

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 578799206  349 VLYDYDAANSTELSLLADEVITVfsVVGMDSDWLMGERGNQKGKVPITYLE 399
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITV--IEESEDGWWEGINTGRTGLVPANYVE 49

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 578799206  24 QFTEEKLGQAEKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEKLDRKAPSRINNPELLGQYMID 103
Cdd:cd07594    1 QFTEEKLGTAEKTEYDAHFENLLQRADKTKVWTEKILKQTEAVLQPNPNVRVEDFIYEKLDRKKPDRLSNLEQLGQAMIE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206 104 AGTEFGPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAK 183
Cdd:cd07594   81 AGNDFGPGTAYGSALIKVGQAQKKLGQAEREFIQTSSSNFLQPLRNFLEGDMKTISKERKLLENKRLDLDACKTRVKKAK 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206 184 AAETRNsqlnsarlegdnimvnfsymlnflhvkwlkiwaeevtKSEQELRITQSEFDRQAEITRLLLEGISSTHAHHLRC 263
Cdd:cd07594  161 SAEAIE-------------------------------------QAEQDLRVAQSEFDRQAEITKLLLEGISSTHANHLRC 203

                        250       260
                 ....*....|....*....|....*.
gi 578799206 264 LNDFVEAQMTYYAQCYQYMLDLQKQL 289
Cdd:cd07594  204 LRDFVEAQMTYYAQCYQYMDDLQRQL 229

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206   19 LSRAVQFTEEKLGQAEKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEkldrkapsriNNPELLG 98
Cdd:pfam03114   5 FNRASQLLGEKVGGAEKTKLDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTVLE----------QPEELLA 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206   99 QYMIDAGTEFGPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIeGDYKTIAKERKLLQNKRLDLDAAKTR 178
Cdd:pfam03114  75 ESMIEAGKDLGEDSSFGKALEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLL-KEFKEIQKHRKKLERKRLDYDAAKTR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206  179 LKKAKAAETRNSQLNSarlegdnimvnfsymlnflhvkwlkiwaeevtKSEQELRITQSEFDRQAEITRLLLEGISSTHA 258
Cdd:pfam03114 154 VKKAKKKKSSKAKDES--------------------------------QAEEELRKAQAKFEESNEQLKALLPNLLSLEV 201

                         250       260       270
                  ....*....|....*....|....*....|....
gi 578799206  259 HHL-RCLNDFVEAQMTYYAQCYQYMLDLQKQLGS 291
Cdd:pfam03114 202 EFVvNQLVAFVEAQLDFHRQCYQLLEQLQQQLGK 235

Src homology 3 domain of Endophilin-B1; Endophilin-B1, also called Bax-interacting factor 1 (Bif-1) or SH3GLB1 (SH3-domain GRB2-like endophilin B1), is localized mainly to the Golgi apparatus. It is involved in the regulation of many biological events including autophagy, tumorigenesis, nerve growth factor (NGF) trafficking, neurite outgrowth, mitochondrial outer membrane dynamics, and cell death. 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-B1 forms homo- and heterodimers (with endophilin-B2) through its BAR domain. It 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578799206 342 SGSRKARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITYLELLN 402
Cdd:cd11945    1 SGSRKARVLYDYDAANSTELSLLADEVITVYSVPGMDSDWLMGERGNQKGKVPITYLELLN 61

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 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITYLEL 400
Cdd:cd11944    1 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNQKGKVPVTYLEL 55

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 578799206  48 KAECTKIWTEKIMKQTEVLLQPNPnarieefvyekldrkapSRINNPELLGQYMIDAGTEFGP--GTAYGNALIKCGETQ 125
Cdd:cd07307    1 KLDELEKLLKKLIKDTKKLLDSLK-----------------ELPAAAEKLSEALQELGKELPDlsNTDLGEALEKFGKIQ 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206 126 KRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAKAAETRNSQLNSArlegdnimvn 205
Cdd:cd07307   64 KELEEFRDQLEQKLENKVIEPLKEYLKKDLKEIKKRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEA---------- 133

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206 206 fsymlnflhvkwlkiwaeevtksEQELRITQSEFDRQAEITRLLLEGISSTHAHHLR-CLNDFVEAQMTYYAQCYQYMLD 284
Cdd:cd07307  134 -----------------------EEELQEAKEKYEELREELIEDLNKLEEKRKELFLsLLLSFIEAQSEFFKEVLKILEQ 190

                 ....
gi 578799206 285 LQKQ 288
Cdd:cd07307  191 LLPY 194

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 578799206  34 EKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEKLDR-----KAPSRINNPELLGQYMIDAGTEF 108
Cdd:cd07613    1 EGTKLDDDFKEMERKVDVTSRAVMEIMTKTIEYLQPNPASRAKLSMINTMSKirgqeKGPGYPQAEALLAEAMLKFGREL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206 109 GPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAKAAETR 188
Cdd:cd07613   81 GDECNFGPALGDVGEAMRELSEVKDSLDMEVKQNFIDPLQNLHDKDLREIQHHLKKLEGRRLDFDYKKKRQGKIPDEELR 160

                 ..
gi 578799206 189 NS 190
Cdd:cd07613  161 QA 162

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 578799206  34 EKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEKLDR-----KAPSRINNPELLGQYMIDAGTEF 108
Cdd:cd07615    1 EGTKLDDDFQEMERKIDVTNKVVAELLSKTTEYLQPNPAYRAKLGMLNTVSKirgqvKTTGYPQTEGLLGDCMLRYGREL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206 109 GPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAKAAETR 188
Cdd:cd07615   81 GEESTFGNALLDVGESMKQMAEVKDSLDINVKQNFIDPLQLLQDKDLKEIGHHLKKLEGRRLDFDYKKKRQGKIPDEEIR 160

                 ..
gi 578799206 189 NS 190
Cdd:cd07615  161 QA 162

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 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGE-RGNQKGKVPITY 397
Cdd:cd00174    1 YARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGElNGGREGLFPANY 51

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 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSvVGMDSDWLMGErgNQKGKV---PITYLE 399
Cdd:cd11763    1 KVRALYDFDSQPSGELSLRAGEVLTITR-QDVGDGWLEGR--NSRGEVglfPSSYVE 54

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 578799206  346 KARVLYDYDAANSTELSLLADEVITVFSvvGMDSDWLMGERGNQKGKVPITYLELL 401
Cdd:pfam07653   1 YGRVIFDYVGTDKNGLTLKKGDVVKVLG--KDNDGWWEGETGGRVGLVPSTAVEEI 54

The Bin/Amphiphysin/Rvs (BAR) domain of Saccharomyces cerevisiae Golgi vesicle protein of 36 kDa 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. Proteomic analysis shows that Golgi vesicle protein of 36 kDa (Gvp36) may be involved in vesicular trafficking and nutritional adaptation. A Saccharomyces cerevisiae strain deficient in Gvp36 shows defects in growth, in actin cytoskeleton polarization, in endocytosis, in vacuolar biogenesis, and in the cell cycle. 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 578799206 115 GNALIKCGETQKRIGTADRE---LIQTsalNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAKAA------ 185
Cdd:cd07600  106 SKALGKYSDAEEKIAEARLEqdqLIQK---EFNAKLRETLNTSFQKAHKARKKVEDKRLQLDTARAELKSAEPAekqeaa 182

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578799206 186 ----ETRNSQLNSARLEGDNIMvnfsymlnflhvkwlkiwaEEVTKSeqelritqSEFdrqaeitrlllegissthahhL 261
Cdd:cd07600  183 rvevETAEDEFVSATEEAVELM-------------------KEVLDN--------PEP---------------------L 214

                        170       180
                 ....*....|....*....|....*...
gi 578799206 262 RCLNDFVEAQMTYYAQCYQYMLDLQKQL 289
Cdd:cd07600  215 QLLKELVKAQLAYHKTAAELLEELLSVL 242

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGERGNQKGKVPITYLEL 400
Cdd:cd11781    1 KARALYPFKAQSAKELSLKKGDIIYIRRQI--DKNWYEGEHNGRVGIFPASYVEI 53

Second Src Homology 3 domain of Sorbin and SH3 domain containing (Sorbs) proteins and similar domains; This family, also called the vinexin family, is composed predominantly of adaptor proteins containing one sorbin homology (SoHo) and three SH3 domains. Members include the second SH3 domains of Sorbs1 (or ponsin), Sorbs2 (or ArgBP2), Vinexin (or Sorbs3), and similar domains. They are involved in the regulation of cytoskeletal organization, cell adhesion, and growth factor signaling. Members of this family bind multiple partners including signaling molecules like c-Abl, c-Arg, Sos, and c-Cbl, as well as cytoskeletal molecules such as vinculin and afadin. They may have overlapping functions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGERGNQKGKVPITYLE 399
Cdd:cd11782    1 EARAKYNFNADTGVELSFRKGDVITLTRRV--DENWYEGRIGGRQGIFPVSYVQ 52

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

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gi 578799206 346 KARVLYDYDAANSTELSLLADEVITvfSVVGMDSDWLMGERGNQKGKVPITY 397
Cdd:cd11818    1 KARALYDFTGENEDELSFKAGDIIT--ELESIDEEWMSGELRGKSGIFPKNF 50

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.

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gi 578799206 347 ARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGERGNQKGKVPITYLEL 400
Cdd:cd11961    2 AKALYDYDAAEDNELSFFENDKIINIEFV--DDDWWLGECHGSRGLFPSNYVEL 53

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

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gi 578799206 348 RVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITYLELL 401
Cdd:cd12057    3 KVLFPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRGVFPDNFVKLL 56

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGERGNQK-GKVPITYLEL 400
Cdd:cd11960    1 RARALYDYQAADDTEISFDPGDIITDIEQI--DEGWWRGTGPDGTyGLFPANYVEL 54

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 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITYLEL 400
Cdd:cd11842    1 KAVALYDFAGEQPGDLAFQKGDIITILKKSDSQNDWWTGRIGGREGIFPANYVEL 55

Src Homology 3 domain of Sorting Nexin 33; SNX33 interacts with Wiskott-Aldrich syndrome protein (WASP) and plays a role in the maintenance of cell shape and cell cycle progression. It modulates the shedding and endocytosis of cellular prion protein (PrP(c)) and amyloid precursor protein (APP). SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX33 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVGMDSdWLMGE--RGnQKGKVPITYLEL 400
Cdd:cd11896    1 KARALYSFQSENKEEINIQENEELVIFSENSLDG-WLQGQnsRG-ETGLFPASYVEI 55

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

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gi 578799206 345 RKARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGERGNQKGKVPITYLELL 401
Cdd:cd11919    1 RPARAKFDFKAQTLKELPLQKGDIVYIYKQI--DQNWYEGEHHGRVGIFPRSYIELL 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 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSvvGMDSDWLMGERGNQKGKVPITYLEL 400
Cdd:cd11840    1 QVIALFPYTAQNEDELSFQKGDIINVLS--KDDPDWWRGELNGQTGLFPSNYVEP 53

Src Homology 3 domain of Sorting nexin 18; SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1. It binds FIP5 and is required for apical lumen formation. It may also play a role in axonal elongation. SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNX18 also contains BAR and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVGMDSdWLMG--ERGnQKGKVPITYLEL 400
Cdd:cd11897    1 RARALYDFRSENPGEISLREHEVLSLCSEQDIEG-WLEGvnSRG-DRGLFPASYVEV 55

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 578799206 346 KARVLYDYDAANSTELSLLADEVITvfsVVGMD--SDWLMGERGNQK-GKVPITYLEL 400
Cdd:cd11912    1 TAKVLYDYTASGDDEVSISEGEEVT---VLEPDdgSGWTKVRNGSGEeGLVPTSYIEI 55

C-terminal Src Homology 3 domain of the Nebulin family of proteins; Nebulin family proteins contain multiple nebulin repeats, and may contain an N-terminal LIM domain and/or a C-terminal SH3 domain. They have molecular weights ranging from 34 to 900 kD, depending on the number of nebulin repeats, and they all bind actin. They are involved in the regulation of actin filament architecture and function as stabilizers and scaffolds for cytoskeletal structures with which they associate, such as long actin filaments or focal adhesions. Nebulin family proteins that contain a C-terminal SH3 domain include the giant filamentous protein nebulin, nebulette, Lasp1, and Lasp2. Lasp2, also called LIM-nebulette, is an alternatively spliced variant of nebulette. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578799206 348 RVLYDYDAANSTELSLLADEVITvfSVVGMDSDWLMG--ERGNQKGKVPITYLEL 400
Cdd:cd11789    3 RAMYDYAAADDDEVSFQEGDVII--NVEIIDDGWMEGtvQRTGQSGMLPANYVEL 55

Src homology 3 domain of Signal Transducing Adaptor Molecules; STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. There are two vertebrate STAMs, STAM1 and STAM2, which may be functionally redundant; vertebrate STAMs contain ITAM motifs. They are part of the endosomal sorting complex required for transport (ESCRT-0). STAM2 deficiency in mice did not cause any obvious abnormality, while STAM1 deficiency resulted in growth retardation. Loss of both STAM1 and STAM2 in mice proved lethal, indicating that STAMs are important for embryonic development. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578799206 345 RKARVLYDYDAANSTELSLLADEVITVFSvvgmDSD--WLMGErgNQKG 391
Cdd:cd11820    1 RKVRALYDFEAAEDNELTFKAGEIITVLD----DSDpnWWKGS--NHRG 43

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 578799206 346 KARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITYLE 399
Cdd:cd11836    1 KYRALYAFEARNPDEISFQPGDIIQVDESQVAEPGWLAGELKGKTGWFPANYVE 54

Src homology 3 domain of Signal Transducing Adaptor Molecule 2; STAM2, also called EAST (Epidermal growth factor receptor-associated protein with SH3 and TAM domain) or Hbp (Hrs binding protein), is part of the endosomal sorting complex required for transport (ESCRT-0). It plays a role in sorting mono-ubiquinated endosomal cargo for trafficking to the lysosome for degradation. It is also involved in the regulation of exocytosis. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 578799206 344 SRKARVLYDYDAANSTELSLLADEVITVFSvvGMDSDWLMGERGNQKGKVPITYL 398
Cdd:cd11963    1 ARKVRALYDFEAVEDNELTFKHGEIIIVLD--DSDANWWKGENHRGVGLFPSNFV 53