Alpha-(1,6)-fucosyltransferase N- and catalytic domains; This entry represents the N-terminal coiled-coil and the catalytic domains of the Alpha-(1,6)-fucosyltransferase (FUT8), an enzyme that catalyzes the transfer of a fucose residue in alpha 1-6 linkage to the N-Acetylglucosamine (GlcNAc) residue in N-glycans. The catalytic domain comprises two structures, an open sheet alpha/beta structure, which contains five helices and three beta- strands at the N-terminal, and a Rossmann fold that contains five helices and five beta-strands at the C-terminal. The latter is conserved among the alpha1,2-, alpha1,6-, and protein O-fucosyltransferases and is similar to GT-B group glycosyltransferases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612    1 MTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKARKLVCNINKGCGYGCQLHHVVYCFMIAYGTQRTLIL 80
Cdd:pfam19745  98 IADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHHVTYCFIVAYATNRTLIL 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612   81 ESQNWRYATGGWETVFRPVSETCTDRSGLSTGHWSGEvNDKNIQVVELPIVDSLHPRPPYLPLAVPEDLADRLLRVHGDP 160
Cdd:pfam19745 178 DSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPLAIPADLAPRLLKLHGNP 256

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612  161 AVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHVEEHFQLLARRMQVDKKR 240
Cdd:pfam19745 257 PVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWVEEYFQQLERRTRVDKRR 336

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612  241 VYLATDDPTLLKEAKTKYSNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCTFSSQVCRVAYEIMQTLH 320
Cdd:pfam19745 337 VYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCTFSSQVCRVAYELMQTRY 416

                         330
                  ....*....|....*
gi 357933612  321 PDASANFHSLDDIYY 335
Cdd:pfam19745 417 PDASDRFHSLDDIYY 431

Alpha-(1,6)-fucosyltransferase N- and catalytic domains; This entry represents the N-terminal coiled-coil and the catalytic domains of the Alpha-(1,6)-fucosyltransferase (FUT8), an enzyme that catalyzes the transfer of a fucose residue in alpha 1-6 linkage to the N-Acetylglucosamine (GlcNAc) residue in N-glycans. The catalytic domain comprises two structures, an open sheet alpha/beta structure, which contains five helices and three beta- strands at the N-terminal, and a Rossmann fold that contains five helices and five beta-strands at the C-terminal. The latter is conserved among the alpha1,2-, alpha1,6-, and protein O-fucosyltransferases and is similar to GT-B group glycosyltransferases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612    1 MTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKARKLVCNINKGCGYGCQLHHVVYCFMIAYGTQRTLIL 80
Cdd:pfam19745  98 IADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHHVTYCFIVAYATNRTLIL 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612   81 ESQNWRYATGGWETVFRPVSETCTDRSGLSTGHWSGEvNDKNIQVVELPIVDSLHPRPPYLPLAVPEDLADRLLRVHGDP 160
Cdd:pfam19745 178 DSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPLAIPADLAPRLLKLHGNP 256

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612  161 AVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHVEEHFQLLARRMQVDKKR 240
Cdd:pfam19745 257 PVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWVEEYFQQLERRTRVDKRR 336

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612  241 VYLATDDPTLLKEAKTKYSNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCTFSSQVCRVAYEIMQTLH 320
Cdd:pfam19745 337 VYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCTFSSQVCRVAYELMQTRY 416

                         330
                  ....*....|....*
gi 357933612  321 PDASANFHSLDDIYY 335
Cdd:pfam19745 417 PDASDRFHSLDDIYY 431

Src homology 3 domain of Alpha1,6-fucosyltransferase (Fut8); Fut8 catalyzes the alpha1,6-linkage of a fucose residue from a donor substrate to N-linked oligosaccharides on glycoproteins in a process called core fucosylation, which is crucial for growth factor receptor-mediated biological functions. Fut8-deficient mice show severe growth retardation, early death, and a pulmonary emphysema-like phenotype. Fut8 is also implicated to play roles in aging and cancer metastasis. It contains an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The SH3 domain of Fut8 is located in the lumen and its role in glycosyl transfer is unclear. 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 357933612 343 NQIAVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVRE 397
Cdd:cd11792    1 NQVAIYPHKPRNHDEIELRVGDIIGVAGNHWDGYSKGRNRRTGKTGLYPSYKVKD 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 357933612   345 IAVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKlGKTGLYPSYKVR 396
Cdd:smart00326   6 RALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR-GKEGLFPSNYVE 56

Alpha-(1,6)-fucosyltransferase N- and catalytic domains; This entry represents the N-terminal coiled-coil and the catalytic domains of the Alpha-(1,6)-fucosyltransferase (FUT8), an enzyme that catalyzes the transfer of a fucose residue in alpha 1-6 linkage to the N-Acetylglucosamine (GlcNAc) residue in N-glycans. The catalytic domain comprises two structures, an open sheet alpha/beta structure, which contains five helices and three beta- strands at the N-terminal, and a Rossmann fold that contains five helices and five beta-strands at the C-terminal. The latter is conserved among the alpha1,2-, alpha1,6-, and protein O-fucosyltransferases and is similar to GT-B group glycosyltransferases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612    1 MTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKARKLVCNINKGCGYGCQLHHVVYCFMIAYGTQRTLIL 80
Cdd:pfam19745  98 IADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHHVTYCFIVAYATNRTLIL 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612   81 ESQNWRYATGGWETVFRPVSETCTDRSGLSTGHWSGEvNDKNIQVVELPIVDSLHPRPPYLPLAVPEDLADRLLRVHGDP 160
Cdd:pfam19745 178 DSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPLAIPADLAPRLLKLHGNP 256

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612  161 AVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHVEEHFQLLARRMQVDKKR 240
Cdd:pfam19745 257 PVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWVEEYFQQLERRTRVDKRR 336

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 357933612  241 VYLATDDPTLLKEAKTKYSNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCTFSSQVCRVAYEIMQTLH 320
Cdd:pfam19745 337 VYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCTFSSQVCRVAYELMQTRY 416

                         330
                  ....*....|....*
gi 357933612  321 PDASANFHSLDDIYY 335
Cdd:pfam19745 417 PDASDRFHSLDDIYY 431

Src homology 3 domain of Alpha1,6-fucosyltransferase (Fut8); Fut8 catalyzes the alpha1,6-linkage of a fucose residue from a donor substrate to N-linked oligosaccharides on glycoproteins in a process called core fucosylation, which is crucial for growth factor receptor-mediated biological functions. Fut8-deficient mice show severe growth retardation, early death, and a pulmonary emphysema-like phenotype. Fut8 is also implicated to play roles in aging and cancer metastasis. It contains an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The SH3 domain of Fut8 is located in the lumen and its role in glycosyl transfer is unclear. 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 357933612 343 NQIAVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVRE 397
Cdd:cd11792    1 NQVAIYPHKPRNHDEIELRVGDIIGVAGNHWDGYSKGRNRRTGKTGLYPSYKVKD 55

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 357933612  346 AVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRklGKTGLYPSYKVR 396
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINT--GRTGLVPANYVE 49

Third Src Homology 3 domain of SH3 domain containing ring finger 2; SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF2. 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 357933612 345 IAVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKV 395
Cdd:cd11784    3 VALHSYSAHRPEELELQKGEGVRVLGKFQEGWLRGLSLVTGRVGIFPSNYV 53

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 357933612 345 IAVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKlGKTGLYPS 392
Cdd:cd00174    3 RALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNG-GREGLFPA 49

Third Src Homology 3 domain of SH3 domain containing ring finger 1 (SH3RF1), SH3RF3, and similar domains; SH3RF1 (or POSH) and SH3RF3 (or POSH2) are scaffold proteins that function as E3 ubiquitin-protein ligases. They contain an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle of SH3RF1 and SH3RF3, and similar domains. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 357933612 345 IAVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYP 391
Cdd:cd11783    3 VALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTSLRTGQSGVFP 49

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
                 ....*....|....*....|....*....|....*....|....*....|
gi 357933612 346 AVYPHKPRTEEEIPMEPGDIIGVA----GNHWDGYSKGINRKLGKTGLYP 391
Cdd:cd11791    4 VLYPYTPQEEDELELVPGDYIYVSpeelDSSSDGWVEGTSWLTGCSGLLP 53

Src homology 3 domain of SH3 and multiple ankyrin repeat domains (Shank) proteins; Shank proteins carry scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains. They bind a variety of membrane and cytosolic proteins, and exist in alternatively spliced isoforms. They are highly enriched in postsynaptic density (PSD) where they interact with the cytoskeleton and with postsynaptic membrane receptors including NMDA and glutamate receptors. They are crucial in the construction and organization of the PSD and dendritic spines of excitatory synapses. There are three members of this family (Shank1, Shank2, Shank3) which show distinct and cell-type specific patterns of expression. Shank1 is brain-specific; Shank2 is found in neurons, glia, endocrine cells, liver, and kidney; Shank3 is widely expressed. The SH3 domain of Shank binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands. 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 357933612 345 IAVYPHKPRTEEEIPMEPGDIIGV----AGNHWDGYSKginrklGKTGLYPSY 393
Cdd:cd11832    3 IAVKSYSPQEEGEISLHKGDRVKVlsigEGGFWEGSVR------GRTGWFPSD 49

Third (or C-terminal) Src Homology 3 domain of Vinexin, also called Sorbin and SH3 domain containing 3 (Sorbs3); Vinexin is also called Sorbs3, SH3P3, and SH3-containing adapter molecule 1 (SCAM-1). It is an adaptor protein containing one sorbin homology (SoHo) and three SH3 domains. Vinexin was first identified as a vinculin binding protein; it is co-localized with vinculin at cell-ECM and cell-cell adhesion sites. There are several splice variants of vinexin: alpha, which contains the SoHo and three SH3 domains and displays tissue-specific expression; and beta, which contains only the three SH3 domains and is widely expressed. Vinexin alpha stimulates the accumulation of F-actin at focal contact sites. Vinexin also promotes keratinocyte migration and wound healing. The SH3 domains of vinexin have been reported to bind a number of ligands including vinculin, WAVE2, DLG5, Abl, and Cbl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 357933612 346 AVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYP 391
Cdd:cd11918    6 AVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGVSRRTQKFGTFP 51

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 357933612 346 AVYPHKPRTEEEIPMEPGDIIGVAGNH-----WDGYSKGinrklGKTGLYP 391
Cdd:cd11836    4 ALYAFEARNPDEISFQPGDIIQVDESQvaepgWLAGELK-----GKTGWFP 49

Second Src Homology 3 domain (SH3B) 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 second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A 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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 357933612 347 VYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRklGKTGLYPSYKVRE 397
Cdd:cd12054    6 LFEYVPQNEDELELKVGDIIDINEEVEEGWWSGTLN--GKSGLFPSNFVKE 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 357933612 346 AVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVR 396
Cdd:cd11916    6 ALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSRRTKQFGTFPGNYVK 56

Src Homology 3 domain of Cdc42-Interacting Protein 4, Bzz1 and similar domains; This subfamily is composed of Cdc42-Interacting Protein 4 (CIP4) and similar proteins such as Formin Binding Protein 17 (FBP17) and FormiN Binding Protein 1-Like (FNBP1L), as well as yeast Bzz1 (or Bzz1p). CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis. CIP4 and FBP17 bind to the Fas ligand and may be implicated in the inflammatory response. CIP4 may also play a role in phagocytosis. Bzz1 is also 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. Members of this subfamily contain an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain as well as at least one C-terminal SH3 domain. Bzz1 contains a second SH3 domain at the C-terminus. 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 357933612 346 AVYPHKPRTEEEIPMEPGDIIG-VAGNHWDGYSKgINRKLGKTGLYPSYKVR 396
Cdd:cd11777    4 ALYAFVGSSEGTISMTEGEKLSlVEEDKGDGWTR-VRRDTGEEGYVPTSYIR 54

Third (or C-terminal) 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 357933612 346 AVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVR 396
Cdd:cd11917    9 ALYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSRRTKFFGTFPGNYVK 59

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 357933612 346 AVYPHKPRTEEEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYP 391
Cdd:cd11780    4 ALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGTSERTGLFGTFP 49