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 1824163874 342 SNNRKARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGK 392
Cdd:cd11945     1 SGSRKARVLYDYDAANSTELSLLADEVITVYSVPGMDSDWLMGERGNQKGK 51

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 1824163874  19 LSRAVQFTEEKLGQAEKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEkldrkapsriNNPELLG 98
Cdd:pfam03114   5 FNRASQLLGEKVGGAEKTKLDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTVLE----------QPEELLA 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874  99 QYMIDAGTEFGPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIeGDYKTIAKERKLLQNKRLDLDAAKTR 178
Cdd:pfam03114  75 ESMIEAGKDLGEDSSFGKALEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLL-KEFKEIQKHRKKLERKRLDYDAAKTR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 179 LKKAKAAETKSSQLNSarpegdnimvnfsymlnflhvkwlkiwaeevtKSEQELRITQSEFDRQAEITRLLLEGISSTHA 258
Cdd:pfam03114 154 VKKAKKKKSSKAKDES--------------------------------QAEEELRKAQAKFEESNEQLKALLPNLLSLEV 201

                         250       260       270
                  ....*....|....*....|....*....|....
gi 1824163874 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1824163874 342 SNNRKARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGK 392
Cdd:cd11945     1 SGSRKARVLYDYDAANSTELSLLADEVITVYSVPGMDSDWLMGERGNQKGK 51

Variant SH3 domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1824163874 349 VLYDYDAANSTELSLLADEVITVfsVVGMDSDWLMGERGNQKG 391
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITV--IEESEDGWWEGINTGRTG 41

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 1824163874  24 QFTEEKLGQAEKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEKLDRKAPSRINNPELLGQYMID 103
Cdd:cd07594     1 QFTEEKLGTAEKTEYDAHFENLLQRADKTKVWTEKILKQTEAVLQPNPNVRVEDFIYEKLDRKKPDRLSNLEQLGQAMIE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 104 AGTEFGPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAK 183
Cdd:cd07594    81 AGNDFGPGTAYGSALIKVGQAQKKLGQAEREFIQTSSSNFLQPLRNFLEGDMKTISKERKLLENKRLDLDACKTRVKKAK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 184 AAETKSsqlnsarpegdnimvnfsymlnflhvkwlkiwaeevtKSEQELRITQSEFDRQAEITRLLLEGISSTHAHHLRC 263
Cdd:cd07594   161 SAEAIE-------------------------------------QAEQDLRVAQSEFDRQAEITKLLLEGISSTHANHLRC 203

                         250       260
                  ....*....|....*....|....*.
gi 1824163874 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 1824163874  19 LSRAVQFTEEKLGQAEKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEkldrkapsriNNPELLG 98
Cdd:pfam03114   5 FNRASQLLGEKVGGAEKTKLDEDFEELERRFDTTEKEIKKLQKDTKGYLQPNPGARAKQTVLE----------QPEELLA 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874  99 QYMIDAGTEFGPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIeGDYKTIAKERKLLQNKRLDLDAAKTR 178
Cdd:pfam03114  75 ESMIEAGKDLGEDSSFGKALEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLL-KEFKEIQKHRKKLERKRLDYDAAKTR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 179 LKKAKAAETKSSQLNSarpegdnimvnfsymlnflhvkwlkiwaeevtKSEQELRITQSEFDRQAEITRLLLEGISSTHA 258
Cdd:pfam03114 154 VKKAKKKKSSKAKDES--------------------------------QAEEELRKAQAKFEESNEQLKALLPNLLSLEV 201

                         250       260       270
                  ....*....|....*....|....*....|....
gi 1824163874 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
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1824163874 342 SNNRKARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGK 392
Cdd:cd11945     1 SGSRKARVLYDYDAANSTELSLLADEVITVYSVPGMDSDWLMGERGNQKGK 51

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-A; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Endophilins are accessory proteins, localized at synapses, which interact with the endocytic proteins, dynamin and synaptojanin. They are essential for synaptic vesicle formation from the plasma membrane. They interact with voltage-gated calcium channels, thus linking vesicle endocytosis to calcium regulation. They also play roles in virus budding, mitochondrial morphology maintenance, receptor-mediated endocytosis inhibition, and endosomal sorting. Endophilins contain an N-terminal N-BAR domain (BAR domain with an additional N-terminal amphipathic helix), followed by a variable region containing proline clusters, and a C-terminal SH3 domain. They are classified into two types, A and B. Vertebrates contain three endophilin-A isoforms. Endophilin-A proteins are enriched in the brain and play multiple roles in receptor-mediated endocytosis. They tubulate membranes and regulate calcium influx into neurons to trigger the activation of the endocytic machinery. They are also involved in the sorting of plasma membrane proteins, actin filament assembly, and the uncoating of clathrin-coated vesicles for fusion with endosomes. The BAR domains of endophilin-A1 and A3 form crescent-shaped dimers that can detect membrane curvature and drive membrane bending.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874  34 EKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFV---YEKLDRKAPS-RINNPE-LLGQYMIDAGTEF 108
Cdd:cd07592     1 EGTKLDDEFLEMERKTDATSKLVEDLIPKTKEYLQPNPAARAKLAMqntYSKIRGQAKStKYPQPEgLLGEVMLKYGREL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 109 GPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAkaaetk 188
Cdd:cd07592    81 GEDSNFGQALVEVGEALKQLAEVKDSLDDNVKQNFLDPLQQLQDKDLKEINHHRKKLEGRRLDYDYKKRKQGKG------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 189 ssqlnsarpegdnimvnfsymlnflhvkwlkiwaeevtkSEQELRITQSEFDRQAEITRLLLEGISSTHAHHLRCLNDFV 268
Cdd:cd07592   155 ---------------------------------------PDEELKQAEEKFEESKELAENSMFNLLENDVEQVSQLSALV 195

                         250       260
                  ....*....|....*....|.
gi 1824163874 269 EAQMTYYAQCYQYMLDLQKQL 289
Cdd:cd07592   196 EAQLDYHRQSAEILEELQSKL 216

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 1824163874  48 KAECTKIWTEKIMKQTEVLLQPNPnarieefvyekldrkapSRINNPELLGQYMIDAGTEFGP--GTAYGNALIKCGETQ 125
Cdd:cd07307     1 KLDELEKLLKKLIKDTKKLLDSLK-----------------ELPAAAEKLSEALQELGKELPDlsNTDLGEALEKFGKIQ 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 126 KRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAKAAETKSSQLNSArpegdnimvn 205
Cdd:cd07307    64 KELEEFRDQLEQKLENKVIEPLKEYLKKDLKEIKKRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEA---------- 133

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 206 fsymlnflhvkwlkiwaeevtksEQELRITQSEFDRQAEITRLLLEGISSTHAHHLR-CLNDFVEAQMTYYAQCYQYMLD 284
Cdd:cd07307   134 -----------------------EEELQEAKEKYEELREELIEDLNKLEEKRKELFLsLLLSFIEAQSEFFKEVLKILEQ 190

                  ....
gi 1824163874 285 LQKQ 288
Cdd:cd07307   191 LLPY 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 1824163874  28 EKLGQAEKTE-LDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEefvyeklDRKapsrINNPE-LLGQYMIDAG 105
Cdd:cd07595     2 QTVGRAEKTEvLSDELLQIEKRVEAVKDACQNIHKKLISCLQGQSGEDKD-------KRL----KKLPEyGLAQSMLESS 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 106 TEFGPGTAYGNALIKCGETQKRIGtadRELIQTSAL---NFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKA 182
Cdd:cd07595    71 KELPDDSLLGKVLKLCGEAQNTLA---RELVDHEMNveeDVLSPLQNILEVEIPNIQKQKKRLSKLVLDMDSARSRYNAA 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 183 KaaetKSSQLNSARPEGDNImvnfsymlnflhvkwlkiwaeevtKSEQE---LRITQSefdrQAEITRLLLEgISSTHAH 259
Cdd:cd07595   148 H----KSSGGQGAAAKVDAL------------------------KDEYEeaeLKLEQC----RDALATDMYE-FLAKEAE 194

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1824163874 260 HLRCLNDFVEAQMTYYAQC---YQYML-DLQKQLGSFPSN 295
Cdd:cd07595   195 IASYLIDLIEAQREYHRTAlsvLEAVLpELQEQIEQSPSK 234

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 1824163874  34 EKTELDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEEFVYEKLDR-----KAPSRINNPELLGQYMIDAGTEF 108
Cdd:cd07615     1 EGTKLDDDFQEMERKIDVTNKVVAELLSKTTEYLQPNPAYRAKLGMLNTVSKirgqvKTTGYPQTEGLLGDCMLRYGREL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 109 GPGTAYGNALIKCGETQKRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAKAAETK 188
Cdd:cd07615    81 GEESTFGNALLDVGESMKQMAEVKDSLDINVKQNFIDPLQLLQDKDLKEIGHHLKKLEGRRLDFDYKKKRQGKIPDEEIR 160

                         170       180
                  ....*....|....*....|
gi 1824163874 189 SS--QLNSARPEGDNIMVNF 206
Cdd:cd07615   161 QAveKFEESKELAERSMFNF 180

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1824163874 346 KARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGE-RGNQKG 391
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGElNGGREG 45

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
                   ....*....|....*....|....*....|....*....|....*.
gi 1824163874  345 RKARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGERGNQK 390
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVLEKS--DDGWWKGRLGRGK 46

The Bin/Amphiphysin/Rvs (BAR) domain of RhoGAP interacting with CIP4 homologs protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. RhoGAP interacting with CIP4 homologs protein 2 (Rich2) is a Rho GTPase activating protein that interacts with CD317, a lipid raft-associated integral membrane protein. It plays a role in actin cytoskeleton organization and the maintenance of microvilli in polarized epithelial cells. Rich2 contains an N-terminal BAR domain followed by a GAP domain for Rho and Rac GTPases and a C-terminal proline-rich domain. 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 1824163874  28 EKLGQAEKTE-LDAHLENLLSKAECTKIWTEKIMKQTEVLLQPNPNARIEefvyeKLDRKAPSRInnpelLGQYMIDAGT 106
Cdd:cd07619     2 QTVGRAEKTEvLSEDLLQVEKRLELVKQVSHSTHKKLTACLQGQQGVDAD-----KRSKKLPLTT-----LAQCMVEGAA 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1824163874 107 EFGPGTAYGNALIKCGETQKRIGtadRELIQ---TSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLKKAK 183
Cdd:cd07619    72 VLGDDSLLGKMLKLCGETEDKLA---QELILfelQIERDVVEPLYVLAEVEIPNIQKQRKHLAKLVLDMDSSRTRWQQSS 148

                         170
                  ....*....|....*....
gi 1824163874 184 AAETKSSQLNSARPEGDNI 202
Cdd:cd07619   149 KSSGLSSNLQPTGAKADAL 167

Variant SH3 domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1824163874 349 VLYDYDAANSTELSLLADEVITVfsVVGMDSDWLMGERGNQKG 391
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITV--IEESEDGWWEGINTGRTG 41

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1824163874 347 ARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGE-RGNQKG 391
Cdd:cd11819     2 AKALYDYQAAEDNEISFVEGDIITQIEQI--DEGWWLGVnAKGQKG 45

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 1824163874 346 KARVLYDYDAANSTELSLLADEVITvfSVVGMDSDWLMGERGNQKG 391
Cdd:cd11818     1 KARALYDFTGENEDELSFKAGDIIT--ELESIDEEWMSGELRGKSG 44

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 1824163874 345 RKARVLYDYDAANSTELSLLADEVITVFSvvgmDSD--WLMGErgNQKG 391
Cdd:cd11820     1 RKVRALYDFEAAEDNELTFKAGEIITVLD----DSDpnWWKGS--NHRG 43

Src homology 3 domain of Proline-Serine-Threonine Phosphatase-Interacting Protein 1; PSTPIP1, also called CD2 Binding Protein 1 (CD2BP1), is mainly expressed in hematopoietic cells. It is a binding partner of the cell surface receptor CD2 and PTP-PEST, a tyrosine phosphatase which functions in cell motility and Rac1 regulation. It also plays a role in the activation of the Wiskott-Aldrich syndrome protein (WASP), which couples actin rearrangement and T cell activation. Mutations in the gene encoding PSTPIP1 cause the autoinflammatory disorder known as PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) syndrome. PSTPIP1 contains an N-terminal F-BAR domain, PEST motifs, 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 1824163874 346 KARVLYDYDAANSTELSLLADEVITVfsVVGMDSDWLMGERGNQKG 391
Cdd:cd11824     1 KYSVLYDYTAQEDDELSISKGDVVAV--IEKGEDGWWTVERNGQKG 44

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.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1824163874 346 KARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMG 384
Cdd:cd11960     1 RARALYDYQAADDTEISFDPGDIITDIEQI--DEGWWRG 37

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 1824163874 345 RKARVLYDYDAANSTELSLLADEVITVFSvvGMDSDWLMGErgNQKG 391
Cdd:cd11963     2 RKVRALYDFEAVEDNELTFKHGEIIIVLD--DSDANWWKGE--NHRG 44

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 1824163874 348 RVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKG 391
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTLISKDCIDAGWWEGELNGRRG 46

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 1824163874 347 ARVLYDYDAANSTELSLLADEVITVFSVVgmDSDWLMGERGNQKG 391
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFV--DDDWWLGECHGSRG 44

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

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gi 1824163874 346 KARVLYDYDAANSTELSLLADEVITVFSVvgMDSDW-LMGERGNQKG 391
Cdd:cd11774     1 QAKALYDYDKQTEEELSFNEGDTLDVYDD--SDSDWiLVGFNGTQFG 45

Src Homology 3 domain of Epidermal growth factor receptor kinase substrate 8 and similar proteins; This group is composed of Eps8 and Eps8-like proteins including Eps8-like 1-3, among others. These proteins contain N-terminal Phosphotyrosine-binding (PTB), central SH3, and C-terminal effector domains. Eps8 binds either Abi1 (also called E3b1) or Rab5 GTPase activating protein RN-tre through its SH3 domain. With Abi1 and Sos1, it becomes part of a trimeric complex that is required to activate Rac. Together with RN-tre, it inhibits the internalization of EGFR. The SH3 domains of Eps8 and similar proteins recognize peptides containing a PxxDY motif, instead of the classical PxxP motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity. 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 1824163874 347 ARVLYDYDAANSTELSLLADEVITV 371
Cdd:cd11764     2 VRVLYDFTARNSKELSVLKGEYLEV 26

First Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1824163874 346 KARVLYDYDAANSTELSLLADEVITVFSVVGMDsDWLMGErgNQKGK 392
Cdd:cd11761     3 TCKVLYSYEAQRPDELTITEGEELEVIEDGDGD-GWVKAR--NKSGE 46

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2 (GRB2) and related proteins; This family includes the adaptor protein GRB2 and related proteins including Drosophila melanogaster Downstream of receptor kinase (DRK), Caenorhabditis elegans Sex muscle abnormal protein 5 (Sem-5), GRB2-related adaptor protein (GRAP), GRAP2, and similar proteins. Family members contain an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. GRB2/Sem-5/DRK is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. GRAP2 plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. GRAP acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway. The C-terminal SH3 domains (SH3c) of GRB2 and GRAP2 have been shown to bind to classical PxxP motif ligands, as well as to non-classical motifs. GRB2 SH3c binds Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, while the SH3c of GRAP2 binds to the phosphatase-like protein HD-PTP via a RxxxxK motif. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1824163874 346 KARVLYDYDAANSTELSLLADEVITVFSvvGMDSDWLMGERGNQKG 391
Cdd:cd11805     1 RVQALYDFNPQEPGELEFRRGDIITVLD--SSDPDWWKGELRGRVG 44

Second Src Homology 3 domain of FCH and double SH3 domains proteins; This group is composed of FCH and double SH3 domains protein 1 (FCHSD1) and FCHSD2. These proteins have a common domain structure consisting of an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), two SH3, and C-terminal proline-rich domains. They have only been characterized in silico and their functions remain unknown. This group also includes the insect protein, nervous wreck, which acts as a regulator of synaptic growth signaling. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1824163874 347 ARVLYDYDAANSTELSLLADEVITVFSV--VGMDSDWLMGERGNQKG 391
Cdd:cd11762     2 VRALYDYEAQSDEELSFPEGAIIRILRKddNGVDDGWWEGEFNGRVG 48

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1824163874 346 KARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKG 391
Cdd:cd12142     1 YCRVLFDYNPVAPDELALKKGDVIEVISKETEDEGWWEGELNGRRG 46