Src Homology 3 domain of Amphiphysin I; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDSEADQDAGWLVGVKESDWLQYRDLATYKGLFPENFTRRL 636
Cdd:cd12140     5 VETLHDFEAANSDELELKRGDIVLVVPSETAADQDAGWLTGVKESDWLQYRDASAYKGLFPENFTRRL 72

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439    1 VLQKLGKADETK-DEQFEEYVQNFKRQEAEGTRLQRELRGYL---AAIKGMQEASMKLTESLHEVYEP--DWYGREDVKM 74
Cdd:smart00721  13 VGEKVGKAEKTKlDEDFEELERRFDTTEAEIEKLQKDTKLYLqpnPAVRAKLASQKKLSKSLGEVYEGgdDGEGLGADSS 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439   75 VGEKCDVLWEDFHQKLV----------DGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDE-SRI 143
Cdd:smart00721  93 YGKALDKLGEALKKLLQveeslsqvkrTFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHKLKKAKKSKEKKKdEKL 172

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1796484439  144 SKAEEEFQKAQKVFEEFNVDLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTK 210
Cdd:smart00721 173 AKAEEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQQQLDK 239

Src Homology 3 domain of Amphiphysin I; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDSEADQDAGWLVGVKESDWLQYRDLATYKGLFPENFTRRL 636
Cdd:cd12140     5 VETLHDFEAANSDELELKRGDIVLVVPSETAADQDAGWLTGVKESDWLQYRDASAYKGLFPENFTRRL 72

Variant SH3 domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1796484439 572 LHDFEAANSDELTLQRGDVVLVVPSDSEadqdaGWLVGVKESDWlqyrdlatykGLFPENFTR 634
Cdd:pfam14604   2 LYPYEPKDDDELSLQRGDVITVIEESED-----GWWEGINTGRT----------GLVPANYVE 49

The Bin/Amphiphysin/Rvs (BAR) domain of Amphiphysins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Amphiphysins function primarily in endocytosis and other membrane remodeling events. They contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. This subfamily is composed of different isoforms of amphiphysin and Bridging integrator 2 (Bin2). Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin and synaptojanin. They function in synaptic vesicle endocytosis. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Bin2 is mainly expressed in hematopoietic cells and is upregulated during granulocyte differentiation. The N-BAR domains of amphiphysins form a curved dimer with a positively-charged concave face that can drive membrane bending and curvature.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439   3 QKLGKADETKDEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPDWYGREDVKMVGEKCDVL 82
Cdd:cd07588     1 QKLGKADETRDEVFDEHVNNFNKQQASANRLQKDLKNYLNSVRAMKQASKTLSETLKELYEPDWPGREHLASIFEQLDLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439  83 WEDFHQKLVDGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDESRISKAEEEFQKAQKVFEEFNV 162
Cdd:cd07588    81 WNDLEEKLSDQVLGPLTAYQSQFPEVKKRIAKRGRKLVDYDSARHNLEALKAKKKVDDQKLTKAEEELQQAKKVYEELNT 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1796484439 163 DLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTKLGD 213
Cdd:cd07588   161 ELHEELPALYDSRIAFYVDTLQSIFAAESVFHKEIGKVNTKLNDVMDGLAD 211

BAR domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439    1 VLQKLGKADETK-DEQFEEYVQNFKRQEAEGTRLQRELRGYL---AAIKGMQEASMKLTESLHEVYEP--DWYGREDVKM 74
Cdd:smart00721  13 VGEKVGKAEKTKlDEDFEELERRFDTTEAEIEKLQKDTKLYLqpnPAVRAKLASQKKLSKSLGEVYEGgdDGEGLGADSS 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439   75 VGEKCDVLWEDFHQKLV----------DGSLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQSSKRKDE-SRI 143
Cdd:smart00721  93 YGKALDKLGEALKKLLQveeslsqvkrTFILPLLNFLLGEFKEIKKARKKLERKLLDYDSARHKLKKAKKSKEKKKdEKL 172

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1796484439  144 SKAEEEFQKAQKVFEEFNVDLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEIAVLCHKLYEVMTK 210
Cdd:smart00721 173 AKAEEELRKAKQEFEESNAQLVEELPQLVASRVDFFVNCLQALIEAQLNFHRESYKLLQQLQQQLDK 239

Src Homology 3 domain of Amphiphysin I; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDSEADQDAGWLVGVKESDWLQYRDLATYKGLFPENFTRRL 636
Cdd:cd12140     5 VETLHDFEAANSDELELKRGDIVLVVPSETAADQDAGWLTGVKESDWLQYRDASAYKGLFPENFTRRL 72

Src Homology 3 domain of Amphiphysin and related domains; Amphiphysins function primarily in endocytosis and other membrane remodeling events. They exist in several isoforms and mammals possess two amphiphysin proteins from distinct genes. Amphiphysin I proteins, enriched in the brain and nervous system, contain domains that bind clathrin, Adaptor Protein complex 2 (AP2), dynamin, and synaptojanin. They function in synaptic vesicle endocytosis. Human autoantibodies to amphiphysin I hinder GABAergic signaling and contribute to the pathogenesis of paraneoplastic stiff-person syndrome. Some amphiphysin II isoforms, also called Bridging integrator 1 (Bin1), are localized in many different tissues and may function in intracellular vesicle trafficking. In skeletal muscle, Bin1 plays a role in the organization and maintenance of the T-tubule network. Mutations in Bin1 are associated with autosomal recessive centronuclear myopathy. Amphiphysins contain an N-terminal BAR domain with an additional N-terminal amphipathic helix (an N-BAR), a variable central domain, and a C-terminal SH3 domain. The SH3 domain of amphiphysins bind proline-rich motifs present in binding partners such as dynamin, synaptojanin, and nsP3. It also belongs to a subset of SH3 domains that bind ubiquitin in a site that overlaps with the peptide binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDSEADQDAGWLVGVKESDwlqyrdlaTYKGLFPENFTRRL 636
Cdd:cd11790     5 VRATHDYTAEDTDELTFEKGDVILVIPFDDPEEQDEGWLMGVKEST--------GCRGVFPENFTERI 64

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 1796484439  22 NFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYE-----PDWYGREDVKMVGEKCDVL---WEDFHQKLVDG 93
Cdd:cd07307     1 KLDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKelpdlSNTDLGEALEKFGKIQKELeefRDQLEQKLENK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439  94 SLLTLDTYL-GQFPDIKNRIAKRSRKLVDYDSARHHLEALQSsKRKDESRISKAEEEFQKAQKVFEEFNVDLQEELPSLW 172
Cdd:cd07307    81 VIEPLKEYLkKDLKEIKKRRKKLDKARLDYDAAREKLKKLRK-KKKDSSKLAEAEEELQEAKEKYEELREELIEDLNKLE 159

                         170       180
                  ....*....|....*....|....*.
gi 1796484439 173 SRRVGFYVNTFKNVSSLEAKFHKEIA 198
Cdd:cd07307   160 EKRKELFLSLLLSFIEAQSEFFKEVL 185

The Bin/Amphiphysin/Rvs (BAR) domain of Dynamin Binding Protein; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. DyNamin Binding Protein (DNMBP), also called Tuba, is a Cdc42-specific Guanine nucleotide Exchange Factor (GEF) that binds dynamin and various actin regulatory proteins. It serves as a link between dynamin function, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. DNMBP contains BAR and SH3 domains as well as a Dbl Homology domain (DH domain), which harbors GEF activity. 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 DNMBP may be involved in binding to membranes. The gene encoding DNMBP is a candidate gene for late onset Alzheimer's disease.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439  10 ETKDEQFEEYVQNFKRQEAEGTRLQRELRGYLAAIKGMQEASMKLTESLHEVYEPD--------WYGREDVKMVGEKcdv 81
Cdd:cd07589     1 QTKDKEFDELEKKFGSLEKQVQLVVRNVELYLQHVQESVLVKVLALEVVLDLYPSNhprleskwERFRRVVRGISSK--- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1796484439  82 LWEDFH---QKLVdgsLLTLDTYLGQFPDIKNRIAKRSRKLVDYDSARhhlealqssKRKDESRisKAEEEFQKAQKVFE 158
Cdd:cd07589    78 ALPEFKsrvRKLV---IEPLSSLLKLFSGPQKLIQKRYDKLLDYERYK---------EKKERGG--KVDEELEEAANQYE 143

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1796484439 159 EFNVDLQEELPSLWSRRVGFYVNTFKNVSSLEAKFHKEI 197
Cdd:cd07589   144 ALNAQLKEELPKFNQLTAQLLETCLKSFVELQRDLYDTL 182

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDSEadqDAGWLVGvkesdwlqyrDLATYKGLFPENFT 633
Cdd:cd11875     2 ARVLFDYEAENEDELTLREGDIVTILSKDCE---DKGWWKG----------ELNGKRGVFPDNFV 53

Src Homology 3 domain of Mixed Lineage Kinases; MLKs are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1796484439 572 LHDFEAANSDELTLQRGDVVLVVPSDSEADQDAGWLVGvkesdwlqyrDLATYKGLFPENF 632
Cdd:cd11876     5 LFDYDARGEDELTLRRGQPVEVLSKDAAVSGDEGWWTG----------KIGDKVGIFPSNY 55

Src Homology 3 domain of Mixed Lineage Kinase 4; MLK4 is a Serine/Threonine Kinase (STK), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. MLK4 contains an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1796484439 572 LHDFEAANSDELTLQRGDVVLVVPSDSEADQDAGWLVGVkesdwLQYRdlatyKGLFPENFTRR 635
Cdd:cd12058     5 LYDYEASGEDELSLRRGDVVEVLSQDAAVSGDDGWWAGK-----IRHR-----LGIFPANYVTR 58

Src homology 3 domain of ephexin-1-like SH3 domain containing Rho guanine nucleotide exchange factors; Members of this family contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), and C-terminal SH3 domains. They include the Rho guanine nucleotide exchange factors ARHGEF5, ARHGEF16, ARHGEF19, ARHGEF26, ARHGEF27 (also called ephexin-1), and similar proteins, and are also called ephexins because they interact directly with ephrin A receptors. GEFs interact with Rho GTPases via their DH domains to catalyze nucleotide exchange by stabilizing the nucleotide-free GTPase intermediate. They play important roles in neuronal development. The SH3 domains of ARHGEFs play an autoinhibitory role through intramolecular interactions with a proline-rich region N-terminal to the DH domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVvpSDSEADqdaGWLVGVKesdwlqYRDLAtyKGLFPENFTR 634
Cdd:cd11793     2 VQCVHAYTAQQPDELTLEEGDVVNV--LRKMPD---GWYEGER------LRDGE--RGWFPSSYTE 54

Src Homology 3 domain of fungal BOI-like proteins; This subfamily includes the Saccharomyces cerevisiae proteins BOI1 and BOI2, and similar proteins. They contain an N-terminal SH3 domain, a Sterile alpha motif (SAM), and a Pleckstrin homology (PH) domain at the C-terminus. BOI1 and BOI2 interact with the SH3 domain of Bem1p, a protein involved in bud formation. They promote polarized cell growth and participates in the NoCut signaling pathway, which is involved in the control of cytokinesis. 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDSEADQdaGWLVGvkesdwlqyRDLATYK-GLFPENF 632
Cdd:cd11886     2 LIVIHDFNARSEDELTLKPGDKIELIEDDEEFGD--GWYLG---------RNLRTGEtGLFPVVF 55

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1796484439 570 ETLHDFEAANSDELTLQRGDVVLVVPSDSeadQDAGWLVGvkesdwlqyrDLATYKGLFPENFTRRL 636
Cdd:cd12057     3 KVLFPYEAQNEDELTIKEGDIVTLISKDC---IDAGWWEG----------ELNGRRGVFPDNFVKLL 56

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing proteins, also called TULA (T cell Ubiquitin LigAnd) family of proteins; UBASH3 or TULA proteins are also referred to as Suppressor of T cell receptor Signaling (STS) proteins. They contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. In some vertebrates, there are two TULA family proteins, called UBASH3A (also called TULA or STS-2) and UBASH3B (also called TULA-2 or STS-1), which show partly overlapping as well as distinct functions. UBASH3B is widely expressed while UBASH3A is only found in lymphoid cells. UBASH3A facilitates apoptosis induced in T cells through its interaction with the apoptosis-inducing factor AIF. UBASH3B is an active phosphatase while UBASH3A is not. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1796484439 572 LHDFEAANSDELTLQRGDVVLVVPSDSEADQDaGWLVGVkesDWlqyrdLATYKGLFPENFTRR 635
Cdd:cd11791     5 LYPYTPQEEDELELVPGDYIYVSPEELDSSSD-GWVEGT---SW-----LTGCSGLLPENYTEK 59

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                          10        20        30        40        50        60
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gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVL-VVPSDSEadqdaGWLVGVKESDwlqyrdlatyKGLFPENFTR 634
Cdd:cd11882     2 ARALYACKAEDESELSFEPGQIITnVQPSDEP-----GWLEGTLNGR----------TGLIPENYVE 53

Src homology 3 domain of Signal Transducing Adaptor Molecule 1; STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases, Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPsdseaDQDAGWLVGvkesdwlqyrdlATYK--GLFPENF 632
Cdd:cd11964     3 VRAIYDFEAAEDNELTFKAGDIITILD-----DSDPNWWKG------------ETPQgtGLFPSNF 51

Src homology 3 domain of Ubiquitin-associated and SH3 domain-containing protein A; UBASH3A is also called Cbl-Interacting Protein 4 (CLIP4), T cell Ubiquitin LigAnd (TULA), or T cell receptor Signaling (STS)-2. It is only found in lymphoid cells and exhibits weak phosphatase activity. UBASH3A facilitates T cell-induced apoptosis through interaction with the apoptosis-inducing factor AIF. It is involved in regulating the level of phosphorylation of the zeta-associated protein (ZAP)-70 tyrosine kinase. TULA proteins contain an N-terminal UBA domain, a central SH3 domain, and a C-terminal histidine phosphatase domain. They bind c-Cbl through the SH3 domain and to ubiquitin via UBA. 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 1796484439 567 QHVETLHDFEAANSDELTLQRGDVVLVVPSDSEaDQDAGWLVGVKESdwlqyrdlATYKGLFPENFTRR 635
Cdd:cd11937     1 QTLRALFQYKPQNIDELMLSPGDYIFVDPTQQS-EASEGWVIGISHR--------TGCRGFLPENYTER 60

Second Src Homology 3 domain of Bzz1 and similar domains; Bzz1 (or Bzz1p) is a WASP/Las17-interacting protein involved in endocytosis and trafficking to the vacuole. It physically interacts with type I myosins and functions in the early steps of endocytosis. Together with other proteins, it induces membrane scission in yeast. Bzz1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. This model represents the second 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 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVpsdsEADQDAGWLVGvkesdwlqyrDLATYKGLFPENF 632
Cdd:cd11778     2 VEALYDYEAQGDDEISIRVGDRIAVI----RGDDGSGWTYG----------EINGVKGLFPTSY 51

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 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPsdseaDQDAGWlvgvkesdWLQYRDLATykGLFPENF 632
Cdd:cd11820     3 VRALYDFEAAEDNELTFKAGEIITVLD-----DSDPNW--------WKGSNHRGE--GLFPANF 51

First Src Homology 3 domain (SH3A) 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 first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. 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 1796484439 574 DFEAANSDELTLQRGDVVLVVPSDseadqDAGWLVGvkesdwlqyrDLATYKGLFPENFTR 634
Cdd:cd12052     7 DYKAQHEDELTITVGDIITKIKKD-----DGGWWEG----------EIKGRRGLFPDNFVR 52

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 1796484439 572 LHDFEAANSDELTLQRGDVVLVVpsdsEADQDAGWLV 608
Cdd:cd11824     5 LYDYTAQEDDELSISKGDVVAVI----EKGEDGWWTV 37

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. 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 1796484439 573 HDFEAANSDELTLQRGDVVLVVpsdsEADQDAGWLVGvkesdwlqyrDLATYKGLFPENFTRRL 636
Cdd:cd12053     6 YDYDAVHEDELTIRVGEIIRNV----KKLEEEGWLEG----------ELNGRRGMFPDNFVKEI 55

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 6; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. 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. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX6 forms a stable complex with SNX1 and may be a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, acting as a mammalian equivalent of yeast Vsp17p. It interacts with the receptor serine/threonine kinases from the transforming growth factor-beta family. It also plays roles in enhancing the degradation of EGFR and in regulating the activity of Na,K-ATPase through its interaction with Translationally Controlled Tumor Protein (TCTP). BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

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gi 1796484439  98 LDTYLGQFPDIKNRIAKRSRKLVDYDSARHHLEALQsSKRKDesrISKAEEEFQKAQKVFEEFNVDLQEELPSLWSRRVG 177
Cdd:cd07662   111 LKYYLRESQAAKDLLYRRSRSLVDYENANKALDKAR-AKNKD---VLQAETTQQLCCQKFEKISESAKQELIDFKTRRVA 186

                          90
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gi 1796484439 178 FYVNTFKNVSSLEAKFHK 195
Cdd:cd07662   187 AFRKNLVELAELELKHAK 204

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 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDseadqDAGWLVGvkesdwlqyrDLATYKGLFPENF 632
Cdd:cd11840     2 VIALFPYTAQNEDELSFQKGDIINVLSKD-----DPDWWRG----------ELNGQTGLFPSNY 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.

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gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVPSDSeadqdagwlvgvkESDWLQYRDLATYKGLFPENF 632
Cdd:cd11763     2 VRALYDFDSQPSGELSLRAGEVLTITRQDV-------------GDGWLEGRNSRGEVGLFPSSY 52

Third (or C-terminal) 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 third 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 1796484439 572 LHDFEAANSDELTLQRGDVVLVVPSdseadQDAGWLVGVKESdwlqyrdlaTYK-GLFPENFTRR 635
Cdd:cd11780     5 LYSYTPQNEDELELREGDIVYVMEK-----CDDGWFVGTSER---------TGLfGTFPGNYVAR 55

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. 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 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVpsdseADQDAGWLVGvkesdwlqyrDLATYKGLFPENFTR 634
Cdd:cd11877     2 VRAKFNFEGTNEDELSFDKGDIITVT-----QVVEGGWWEG----------TLNGKTGWFPSNYVK 52

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

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gi 1796484439 572 LHDFEAANSDELTLQRGDVVLVVPSdseadQDAGWLVGVKEsdwlqyRDLATykGLFPENF 632
Cdd:cd11789     5 MYDYAAADDDEVSFQEGDVIINVEI-----IDDGWMEGTVQ------RTGQS--GMLPANY 52

Src homology 3 domain of Protein kinase C and Casein kinase Substrate in Neurons (PACSIN) proteins; PACSINs, also called Synaptic dynamin-associated proteins (Syndapins), act as regulators of cytoskeletal and membrane dynamics. They bind both dynamin and Wiskott-Aldrich syndrome protein (WASP), and may provide direct links between the actin cytoskeletal machinery through WASP and dynamin-dependent endocytosis. Vetebrates harbor three isoforms with distinct expression patterns and specific functions. PACSINs contain an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVpsdSEADqDAGWLVGVKESDwlqyrdlatyKGLFPENF 632
Cdd:cd11843     2 VRALYDYEGQESDELSFKAGDILTKL---EEED-EQGWCKGRLDGR----------VGLYPANY 51

Second 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 1796484439 568 HVETLHDFEAANSDELTLQRGDVVlvvpsdseadqdagWLVGVKESDWlqYR-DLATYKGLFPENFTR 634
Cdd:cd11815     1 HAVVLHDFPAEHSDDLSLNSGEIV--------------YLLEKIDTEW--YRgKCKNTTGIFPANHVK 52

Fourth 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 1796484439 569 VETLHDFEAANSDELTLQRGDVVLVVpsdseADQDAGWLVGVkesdwLQYRDlatykGLFPENF 632
Cdd:cd11817     2 AVALYDFTGETEEDLSFQRGDRILVT-----EHLDAEWSRGR-----LNGRE-----GIFPRAF 50