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 332078497    1 MTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLHHVVYCFMIAYGTQRTLIL 80
Cdd:pfam19745  98 IADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHHVTYCFIVAYATNRTLIL 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497   81 ESQNWRYATGGWETVFRPVSETCTDRSGISTGHWSGEvKDKNVQVVELPIVDSLHPRPPYLPLAVPEDLADRLVRVHGDP 160
Cdd:pfam19745 178 DSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPLAIPADLAPRLLKLHGNP 256

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497  161 AVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHVEEHFQLLARRMQVDKKR 240
Cdd:pfam19745 257 PVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWVEEYFQQLERRTRVDKRR 336

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497  241 VYLATDDPSLLKEAKTKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCTFSSQVCRVAYEIMQTLH 320
Cdd:pfam19745 337 VYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCTFSSQVCRVAYELMQTRY 416

                         330
                  ....*....|....*
gi 332078497  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 332078497    1 MTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLHHVVYCFMIAYGTQRTLIL 80
Cdd:pfam19745  98 IADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHHVTYCFIVAYATNRTLIL 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497   81 ESQNWRYATGGWETVFRPVSETCTDRSGISTGHWSGEvKDKNVQVVELPIVDSLHPRPPYLPLAVPEDLADRLVRVHGDP 160
Cdd:pfam19745 178 DSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPLAIPADLAPRLLKLHGNP 256

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497  161 AVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHVEEHFQLLARRMQVDKKR 240
Cdd:pfam19745 257 PVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWVEEYFQQLERRTRVDKRR 336

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497  241 VYLATDDPSLLKEAKTKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCTFSSQVCRVAYEIMQTLH 320
Cdd:pfam19745 337 VYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCTFSSQVCRVAYELMQTRY 416

                         330
                  ....*....|....*
gi 332078497  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 332078497 343 NQIAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYPSYKVRE 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 332078497   345 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKlGRTGLYPSYKVR 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 332078497    1 MTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLHHVVYCFMIAYGTQRTLIL 80
Cdd:pfam19745  98 IADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHHVTYCFIVAYATNRTLIL 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497   81 ESQNWRYATGGWETVFRPVSETCTDRSGISTGHWSGEvKDKNVQVVELPIVDSLHPRPPYLPLAVPEDLADRLVRVHGDP 160
Cdd:pfam19745 178 DSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPLAIPADLAPRLLKLHGNP 256

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497  161 AVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHVEEHFQLLARRMQVDKKR 240
Cdd:pfam19745 257 PVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWVEEYFQQLERRTRVDKRR 336

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 332078497  241 VYLATDDPSLLKEAKTKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCTFSSQVCRVAYEIMQTLH 320
Cdd:pfam19745 337 VYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCTFSSQVCRVAYELMQTRY 416

                         330
                  ....*....|....*
gi 332078497  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 332078497 343 NQIAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYPSYKVRE 397
Cdd:cd11792    1 NQVAIYPHKPRNHDEIELRVGDIIGVAGNHWDGYSKGRNRRTGKTGLYPSYKVKD 55

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 332078497  346 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRklGRTGLYPSYKVR 396
Cdd:pfam14604   1 ALYPYEPKDDDELSLQRGDVITVIEESEDGWWEGINT--GRTGLVPANYVE 49

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 332078497   345 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKlGRTGLYPSYKVR 396
Cdd:smart00326   6 RALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR-GKEGLFPSNYVE 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
                 ....*....|....*....|....*....|....*....|....*...
gi 332078497 345 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKlGRTGLYPS 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 332078497 345 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 391
Cdd:cd11783    3 VALYPYKPQKPDELELRKGEMYTVTEKCQDGWFKGTSLRTGQSGVFP 49

Third Src Homology 3 domain of SH3 domain containing ring finger 3, an E3 ubiquitin-protein ligase; SH3RF3 is also called POSH2 (Plenty of SH3s 2) or SH3MD4 (SH3 multiple domains protein 4). It is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF3. 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 332078497 345 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 391
Cdd:cd11925    4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSLRTGVSGVFP 50

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 332078497 346 AIYAHQPRTADEIPMEPGDIIGVAGNH-----WDGYSKGvnrklGRTGLYP 391
Cdd:cd11836    4 ALYAFEARNPDEISFQPGDIIQVDESQvaepgWLAGELK-----GKTGWFP 49

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 332078497 345 IAIYAHQPRTADEIPMEPGDIIGV----AGNHWDGYSKgvnrklGRTGLYPSY 393
Cdd:cd11832    3 IAVKSYSPQEEGEISLHKGDRVKVlsigEGGFWEGSVR------GRTGWFPSD 49

Src homology 3 domain of JNK-interacting proteins 1 and 2, and similar domains; JNK-interacting proteins (JIPs) function as scaffolding proteins for c-Jun N-terminal kinase (JNK) signaling pathways. They bind to components of Mitogen-activated protein kinase (MAPK) pathways such as JNK, MKK, and several MAP3Ks such as MLK and DLK. There are four JIPs (JIP1-4); all contain a JNK binding domain. JIP1 and JIP2 also contain SH3 and Phosphotyrosine-binding (PTB) domains. Both are highly expressed in the brain and pancreatic beta-cells. JIP1 functions as an adaptor linking motor to cargo during axonal transport and also is involved in regulating insulin secretion. JIP2 form complexes with fibroblast growth factor homologous factors (FHFs), which facilitates activation of the p38delta MAPK. The SH3 domain of JIP1 homodimerizes at the interface usually involved in proline-rich ligand recognition, despite the lack of this motif in the domain itself. 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 332078497 346 AIYAHQPRTADEIPMEPGDIIGV---AGNHWdgySKGVNRKLGRTGLYPSYKVRE 397
Cdd:cd11801    4 ALHKFIPRHEDEIELDIGDPVYVeqeADDLW---CEGTNLRTGQRGIFPAAYVVE 55

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 332078497 346 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYPSYKVR 396
Cdd:cd11916    6 ALYSYAPQNDDELELRDGDIVDVMEKCDDGWFVGTSRRTKQFGTFPGNYVK 56

C-terminal (Fourth) 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 fourth SH3 domain, located at the C-terminus 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 332078497 346 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYPS 392
Cdd:cd11785    4 VIVPYPPQSEAELELKEGDIVFVHKKREDGWFKGTLQRTGKTGLFPG 50

Third Src Homology 3 domain of SH3 domain containing ring finger 1, an E3 ubiquitin-protein ligase; SH3RF1 is also called POSH (Plenty of SH3s) or SH3MD2 (SH3 multiple domains protein 2). It is a scaffold protein that acts as an E3 ubiquitin-protein ligase. It 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. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. It contains an N-terminal RING finger domain and four SH3 domains. This model represents the third SH3 domain, located in the middle, of SH3RF1. 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 332078497 345 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 391
Cdd:cd11926    3 VAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSMHTSKIGVFP 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 332078497 346 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 391
Cdd:cd11918    6 AVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGVSRRTQKFGTFP 51

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 332078497 346 AIYAHQPRTADEIPMEPGDIIGVA----GNHWDGYSKgvnrklGRTGLYPSYKVRE 397
Cdd:cd11877    4 AKFNFEGTNEDELSFDKGDIITVTqvveGGWWEGTLN------GKTGWFPSNYVKE 53

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) 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. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

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gi 332078497 346 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGvnRKLGRTGLYPSYKVRE 397
Cdd:cd11874    4 VLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEG--KLNGKVGVFPSNFVKE 53

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 332078497 346 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 391
Cdd:cd11780    4 ALYSYTPQNEDELELREGDIVYVMEKCDDGWFVGTSERTGLFGTFP 49