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 1720398430   1 MAEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKArlk 80
Cdd:cd07617    78 MTEAANDFGPGTPYGKTLIKVGETQKRLGAAERDFIHTSSINFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKA--- 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430  81 kakaaeakatlwndEVDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 160
Cdd:cd07617   155 --------------RLKKAEHELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVEAQATYYAQCYRHMLDLQKQL 220

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-B2; 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. 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. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain, which can bind and bend membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430   1 MAEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKArlk 80
Cdd:cd07617    78 MTEAANDFGPGTPYGKTLIKVGETQKRLGAAERDFIHTSSINFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKA--- 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430  81 kakaaeakatlwndEVDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 160
Cdd:cd07617   155 --------------RLKKAEHELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVEAQATYYAQCYRHMLDLQKQL 220

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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 280
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 1720398430  225 RKARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGN-KKGKVPVTYLE 279
Cdd:smart00326   3 PQVRALYDYTAQDPDELSFKKGDIITVLE--KSDDGWWKGRLGRgKEGLFPSNYVE 56

The Bin/Amphiphysin/Rvs (BAR) domain of Endophilin-B2; 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. 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. Endophilin-B2 forms homo- and heterodimers (with endophilin-B1) through its BAR domain, which can bind and bend membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430   1 MAEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKArlk 80
Cdd:cd07617    78 MTEAANDFGPGTPYGKTLIKVGETQKRLGAAERDFIHTSSINFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKA--- 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430  81 kakaaeakatlwndEVDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 160
Cdd:cd07617   155 --------------RLKKAEHELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVEAQATYYAQCYRHMLDLQKQL 220

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430   1 MAEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLK 80
Cdd:cd07616    78 MIDAGNEFGPGTAYGNALIKCGETQKQIGTADRELIQTSAINFLTPLRNFIEGDYKTITKERKLLQNKRLDLDAAKTRLK 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430  81 KAKAAeakatlwnDEVDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 160
Cdd:cd07616   158 KAKVA--------EARAAAEQELRITQSEFDRQAEITRLLLEGISSTHAHHLRCLNDFVEAQMTYYAQCYQYMLDLQKQL 229

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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 280
Cdd:cd11944     1 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNQKGKVPVTYLEL 55

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 1720398430   1 MAEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLeGDWKTISKERRLLQNRRLDLDACKARLK 80
Cdd:pfam03114  77 MIEAGKDLGEDSSFGKALEDYGEALKRLAQLLEQLDDRVETNFLDPLRNLL-KEFKEIQKHRKKLERKRLDYDAAKTRVK 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430  81 KAKAAEAKatLWNDEvDKAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHL-RCLHEFVKSQTTYYAQCYRHMLDLQKQ 159
Cdd:pfam03114 156 KAKKKKSS--KAKDE-SQAEEELRKAQAKFEESNEQLKALLPNLLSLEVEFVvNQLVAFVEAQLDFHRQCYQLLEQLQQQ 232

                  ...
gi 1720398430 160 LGS 162
Cdd:pfam03114 233 LGK 235

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 1720398430   1 MAEAASELG------PSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDA 74
Cdd:cd07307    33 LSEALQELGkelpdlSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKVIEPLKEYLKKDLKEIKKRRKKLDKARLDYDA 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720398430  75 CKARLKKAKAAEAKAtlwnDEVDKAEQELRVAQTEFDrqaEVTRLLLEGISSTHVNHLR----CLHEFVKSQTTYYAQCY 150
Cdd:cd07307   113 AREKLKKLRKKKKDS----SKLAEAEEELQEAKEKYE---ELREELIEDLNKLEEKRKElflsLLLSFIEAQSEFFKEVL 185

                  ....*....
gi 1720398430 151 RHMLDLQKQ 159
Cdd:cd07307   186 KILEQLLPY 194

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 1720398430  225 RKARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGN-KKGKVPVTYLE 279
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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGE-RGNKKGKVPVTY 277
Cdd:cd00174     1 YARALYDYEAQDDDELSFKKGDIITVLEKD--DDGWWEGElNGGREGLFPANY 51

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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLELL 281
Cdd:pfam07653   1 YGRVIFDYVGTDKNGLTLKKGDVVKVLG--KDNDGWWEGETGGRVGLVPSTAVEEI 54

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720398430 227 ARVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGERGNKKGKVPVTYLEL 280
Cdd:cd11961     2 AKALYDYDAAEDNELSFFENDKIINIEFV--DDDWWLGECHGSRGLFPSNYVEL 53

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 1720398430  13 PYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAKAAEAKATLw 92
Cdd:cd07600   104 PLSKALGKYSDAEEKIAEARLEQDQLIQKEFNAKLRETLNTSFQKAHKARKKVEDKRLQLDTARAELKSAEPAEKQEAA- 182

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720398430  93 NDEVDKAEQELrVAQTEfdrqaEVTRLLLEGISSThvNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQL 160
Cdd:cd07600   183 RVEVETAEDEF-VSATE-----EAVELMKEVLDNP--EPLQLLKELVKAQLAYHKTAAELLEELLSVL 242

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 1720398430 227 ARVLYDYEAADSSELALLADELITvySLPGMDPDWLIGE-RGNKKGKVPVTYLEL 280
Cdd:cd11819     2 AKALYDYQAAEDNEISFVEGDIIT--QIEQIDEGWWLGVnAKGQKGLFPANYVEL 54

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 1720398430   1 MAEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLK 80
Cdd:cd07613    73 MLKFGRELGDECNFGPALGDVGEAMRELSEVKDSLDMEVKQNFIDPLQNLHDKDLREIQHHLKKLEGRRLDFDYKKKRQG 152

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720398430  81 KAkaaeakatlwndevdkAEQELRVAQTEFDRQAEVTRLLLEGISSTHVNHLRCLHEFVKSQTTYYAQ 148
Cdd:cd07613   153 KI----------------PDEELRQALEKFDESKEIAESSMFNLLEMDIEQVSQLSALVQAQLEYHKQ 204

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720398430 226 KARVLYDYEAADSSELALLADELITvySLPGMDPDWLIGERGNKKGKVPVTY 277
Cdd:cd11818     1 KARALYDFTGENEDELSFKAGDIIT--ELESIDEEWMSGELRGKSGIFPKNF 50

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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSlPGMDPDWLIGErgNKKGKV---PVTYLE 279
Cdd:cd11763     1 KVRALYDFDSQPSGELSLRAGEVLTITR-QDVGDGWLEGR--NSRGEVglfPSSYVE 54

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 1720398430 226 KARVLYDYEAADSSELALLADELITVYsLPGMDPDWLIgERGNKKGKVPVTYLEL 280
Cdd:cd11824     1 KYSVLYDYTAQEDDELSISKGDVVAVI-EKGEDGWWTV-ERNGQKGLVPGTYLEK 53

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 1720398430 226 KARVLYDYEAADSSELALLADELITvySLPGMDPDWLIGErgNKKGK---VPVTYLEL 280
Cdd:cd11962     1 RAVVLYDYEKDEDNEIELVEGEIVT--NIEMVDEDWWMGT--NSKGEsglFPSNYVEL 54

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

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gi 1720398430 226 KARVLYDYEAADSSELALLADELITVYSLpgMDPDW-LIGERGNKKGKVPVTYL 278
Cdd:cd11774     1 QAKALYDYDKQTEEELSFNEGDTLDVYDD--SDSDWiLVGFNGTQFGFVPANYI 52

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

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gi 1720398430 228 RVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGER-GNKKGKVPV 275
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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLEL 280
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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSlpGMDPDWLIGERGNKKGKVPVTYLEL 280
Cdd:cd11781     1 KARALYPFKAQSAKELSLKKGDIIYIRR--QIDKNWYEGEHNGRVGIFPASYVEI 53

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1720398430 228 RVLYDYEAADSSELALlaDELITVYSLPGMDPDWLIGERGNKKGKVPVTYLE 279
Cdd:cd11772     3 RALYDYEAQHPDELSF--EEGDLLYISDKSDPNWWKATCGGKTGLIPSNYVE 52

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

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gi 1720398430 223 GTRKARVLYDYEAADSSELALLADEliTVYSLPGMDPDWLIG--ERGNKKGKVPVTYLE 279
Cdd:cd11934     1 GGKRYRAVYDYNAADEDEVSFQDGD--TIVNVQQIDDGWMYGtvERTGDTGMLPANYVE 57

C-terminal Src Homology 3 domain of Nebulin; Nebulin is a giant filamentous protein (600-900 kD) that is expressed abundantly in skeletal muscle. It binds to actin thin filaments and regulates its assembly and function. Nebulin was thought to be part of a molecular ruler complex that is critical in determining the lengths of actin thin filaments in skeletal muscle since its length, which varies due to alternative splicing, correlates with the length of thin filaments in various muscle types. Recent studies indicate that nebulin regulates thin filament length by stabilizing the filaments and preventing depolymerization. Mutations in nebulin can cause nemaline myopathy, characterized by muscle weakness which can be severe and can lead to neonatal lethality. Nebulin contains an N-terminal LIM domain, many nebulin repeats/super 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 1720398430 228 RVLYDYEAADSSELALL-ADELITVYSLpgmDPDWLIG--ERGNKKGKVPVTYLE 279
Cdd:cd11933     5 RAMYDYRAADDDEVSFKdGDTIVNVQTI---DEGWMYGtvQRTGKTGMLPANYVE 56

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 1720398430 227 ARVLYDYEAADSSELALLADEliTVYSLPGMDPDWLIGERGNKKGKVPVTYLELL 281
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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSLPgmDPDWLIGERGNKKGKVPVTYLEL 280
Cdd:cd11840     1 QVIALFPYTAQNEDELSFQKGDIINVLSKD--DPDWWRGELNGQTGLFPSNYVEP 53

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

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gi 1720398430 223 GTRKARvlYDYEAADSSELALLADELITVYSLPGMDPDWLIGERGNKKGKVPVTYLE 279
Cdd:cd11977     1 GTAVAR--YNFAARDMRELSLREGDVVRIYSRIGGDQGWWKGETNGRIGWFPSTYVE 55

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

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gi 1720398430 225 RKARVLYDYEAADSSELALLADeliTVYS--LPGMDPDWLIGERGNKKGKVPVTYLELL 281
Cdd:cd12064     1 RKAKALYACKAEHDSELSFTAG---TVFDnvHPSQEPGWLEGTLNGKTGLIPENYVEFL 56

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1720398430 224 TRKARvlYDYEAADSSELALLADELITVYSLPGmDPDWLIGERGNKKGKVPVTYLE 279
Cdd:cd11830     1 TAKAR--YDFCARDMRELSLKEGDVVKIYNKKG-QQGWWRGEINGRIGWFPSTYVE 53

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1720398430 226 KARVLYDYEAADSSELALLADELITVYSlpgMDPD-WLIGERGNKKGKVPVTYLE 279
Cdd:cd11827     1 QCKALYAYDAQDTDELSFNEGDIIEILK---EDPSgWWTGRLRGKEGLFPGNYVE 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) 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. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. 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 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 1720398430 230 LYDYEAADSSELALLADELITVysLPGMDPDWLIGERGNKKGKVPVTYLEL 280
Cdd:cd11995     6 MYDYTAQNDDELAFSKGQIINV--LNKEDPDWWKGELNGQVGLFPSNYVKL 54

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 1720398430 226 KARVLYDYEAADSSELALLADELITVYSLPGMDpDWLIGErgNKKGK---VPVTYLEL 280
Cdd:cd11761     3 TCKVLYSYEAQRPDELTITEGEELEVIEDGDGD-GWVKAR--NKSGEvgyVPENYLQF 57

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. 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 1720398430 227 ARVLYDYEAADSSELALLADELITvySLPGMDPDWLIGERGNKKGK-VPVTYLE 279
Cdd:cd11825     2 VKALYDYRAQRPDELSFCKHAIIT--NVEKEDGGWWRGDYGGKKQKwFPANYVE 53

Inverse (I)-BAR, also known as the IRSp53/MIM homology Domain (IMD), a dimerization module that binds and bends membranes; Inverse (I)-BAR (or IMD) is a member of the Bin/Amphiphysin/Rvs (BAR) domain family. It is a dimerization and lipid-binding module that bends membranes and induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. IMD domains are found in Insulin Receptor tyrosine kinase Substrate p53 (IRSp53), Missing in Metastasis (MIM), and Brain-specific Angiogenesis Inhibitor 1-Associated Protein 2-like (BAIAP2L) proteins. These are multi-domain proteins that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. Most members contain an N-terminal IMD, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C-terminus, exccept for MIM which does not carry an SH3 domain. Some members contain additional domains and motifs. The IMD domain binds and bundles actin filaments, binds membranes and produces membrane protrusions, and interacts with the small GTPase Rac.

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gi 1720398430   2 AEAASELGPSTPYGKTLIKVSEAEKRLGAAERDFIHTASLSFLTPLRNFLEGDWKTISKERRLLQN----RRLDLD 73
Cdd:cd07605    54 GELASQSRGSQELGEALKQIVDTHKSIEASLEQVAKAFHGELILPLEKKLELDQKVINKFEKDYKKeykqKREDLD 129

Src homology 3 domain of Protein arginine N-methyltransferase 2; PRMT2, also called HRMT1L1, belongs to the arginine methyltransferase protein family. It functions as a coactivator to both estrogen receptor alpha (ER-alpha) and androgen receptor (AR), presumably through arginine methylation. The ER-alpha transcription factor is involved in cell proliferation, differentiation, morphogenesis, and apoptosis, and is also implicated in the development and progression of breast cancer. PRMT2 and its variants are upregulated in breast cancer cells and may be involved in modulating the ER-alpha signaling pathway during formation of breast cancer. PRMT2 also plays a role in regulating the function of E2F transcription factors, which are critical cell cycle regulators, by binding to the retinoblastoma gene product (RB). It contains an N-terminal SH3 domain and an AdoMet binding 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 1720398430 229 VLYDYEAADSSELALLADELITVYSLPgmDPDWLIGERGNKKGKVPVTYL 278
Cdd:cd11806     4 AIADFVATDDSQLSFESGDKLLVLRKP--SVDWWWAEHNGCCGYIPASHL 51