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 2163344826  68 RIPDGPIDQGPAAGKVHALEEQLLKAKEQIENYKKQTGDGgLGKDHEILRRRIENGAKELWFFLQSELKKLKNLEGSE-L 146
Cdd:pfam19745   1 RLRRSEESKGIANGRLDSLEDQLVKAKQQIEDYKPSAANG-PSLEHEVLRRRLENGIQELWYYLSSELKKLRKEIDREsL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 147 QRRIDEFLSDLGHQERSIMTDLYYLSQTDGAGDWREKEAKDLTDLVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLH 226
Cdd:pfam19745  80 ANHINEILDLLAEHKRSLIADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLH 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 227 HVVYCFMIAYGTQRTLILESQNWRYATGGWETVFRPVSETCTDRSGTTTGHWSGEaNDKDVQVVELPIVDSLHPRPPYLP 306
Cdd:pfam19745 160 HVTYCFIVAYATNRTLILDSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLP 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 307 LAVPEDLADRLIRVHGDPAVWWVSQFVKYLIRPQPWLEKEIEEATRKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVH 386
Cdd:pfam19745 239 LAIPADLAPRLLKLHGNPPVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVW 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 387 VEERFELLARRMHVDKKRVYLATDDPSLLQEAKSKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVC 466
Cdd:pfam19745 319 VEEYFQQLERRTRVDKRRVYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVC 398

                         410       420       430
                  ....*....|....*....|....*....|...
gi 2163344826 467 TFSSQVCRVAYEIMQTLHPDASAYFHSLDDIYY 499
Cdd:pfam19745 399 TFSSQVCRVAYELMQTRYPDASDRFHSLDDIYY 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 2163344826  68 RIPDGPIDQGPAAGKVHALEEQLLKAKEQIENYKKQTGDGgLGKDHEILRRRIENGAKELWFFLQSELKKLKNLEGSE-L 146
Cdd:pfam19745   1 RLRRSEESKGIANGRLDSLEDQLVKAKQQIEDYKPSAANG-PSLEHEVLRRRLENGIQELWYYLSSELKKLRKEIDREsL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 147 QRRIDEFLSDLGHQERSIMTDLYYLSQTDGAGDWREKEAKDLTDLVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLH 226
Cdd:pfam19745  80 ANHINEILDLLAEHKRSLIADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLH 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 227 HVVYCFMIAYGTQRTLILESQNWRYATGGWETVFRPVSETCTDRSGTTTGHWSGEaNDKDVQVVELPIVDSLHPRPPYLP 306
Cdd:pfam19745 160 HVTYCFIVAYATNRTLILDSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLP 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 307 LAVPEDLADRLIRVHGDPAVWWVSQFVKYLIRPQPWLEKEIEEATRKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVH 386
Cdd:pfam19745 239 LAIPADLAPRLLKLHGNPPVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVW 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 387 VEERFELLARRMHVDKKRVYLATDDPSLLQEAKSKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVC 466
Cdd:pfam19745 319 VEEYFQQLERRTRVDKRRVYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVC 398

                         410       420       430
                  ....*....|....*....|....*....|...
gi 2163344826 467 TFSSQVCRVAYEIMQTLHPDASAYFHSLDDIYY 499
Cdd:pfam19745 399 TFSSQVCRVAYELMQTRYPDASDRFHSLDDIYY 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 2163344826 507 NQIAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVKE 561
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 2163344826  509 IAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKlGKTGLYPSYKVK 560
Cdd:smart00326   6 RALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR-GKEGLFPSNYVE 56

Possible nuclease of RNase H fold, RuvC/YqgF family [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826  41 RELSKILAKLERLKQQNEDLRRmaeslripdgpidqgpaagKVHALEEQLLKAKEQIENYKKQTGDgGLGKDHEI--LRR 118
Cdd:COG2433   413 EEIRRLEEQVERLEAEVEELEA-------------------ELEEKDERIERLERELSEARSEERR-EIRKDREIsrLDR 472

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2163344826 119 RIENgakelwffLQSELKKLKNlEGSELQRRIDE 152
Cdd:COG2433   473 EIER--------LERELEEERE-RIEELKRKLER 497

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 2163344826  68 RIPDGPIDQGPAAGKVHALEEQLLKAKEQIENYKKQTGDGgLGKDHEILRRRIENGAKELWFFLQSELKKLKNLEGSE-L 146
Cdd:pfam19745   1 RLRRSEESKGIANGRLDSLEDQLVKAKQQIEDYKPSAANG-PSLEHEVLRRRLENGIQELWYYLSSELKKLRKEIDREsL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 147 QRRIDEFLSDLGHQERSIMTDLYYLSQTDGAGDWREKEAKDLTDLVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLH 226
Cdd:pfam19745  80 ANHINEILDLLAEHKRSLIADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLH 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 227 HVVYCFMIAYGTQRTLILESQNWRYATGGWETVFRPVSETCTDRSGTTTGHWSGEaNDKDVQVVELPIVDSLHPRPPYLP 306
Cdd:pfam19745 160 HVTYCFIVAYATNRTLILDSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLP 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 307 LAVPEDLADRLIRVHGDPAVWWVSQFVKYLIRPQPWLEKEIEEATRKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVH 386
Cdd:pfam19745 239 LAIPADLAPRLLKLHGNPPVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVW 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2163344826 387 VEERFELLARRMHVDKKRVYLATDDPSLLQEAKSKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVC 466
Cdd:pfam19745 319 VEEYFQQLERRTRVDKRRVYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVC 398

                         410       420       430
                  ....*....|....*....|....*....|...
gi 2163344826 467 TFSSQVCRVAYEIMQTLHPDASAYFHSLDDIYY 499
Cdd:pfam19745 399 TFSSQVCRVAYELMQTRYPDASDRFHSLDDIYY 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 2163344826 507 NQIAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVKE 561
Cdd:cd11792     1 NQVAIYPHKPRNHDEIELRVGDIIGVAGNHWDGYSKGRNRRTGKTGLYPSYKVKD 55

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2163344826 510 AVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRklGKTGLYPSYKVK 560
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 2163344826  509 IAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKlGKTGLYPSYKVK 560
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 2163344826 509 IAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKlGKTGLYPS 556
Cdd:cd00174     3 RALYDYEAQDDDELSFKKGDIITVLEKDDDGWWEGELNG-GREGLFPA 49

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2163344826 509 IAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINrKLGKTGLYPS 556
Cdd:pfam00018   1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRN-KGGKEGLIPS 47

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 2163344826 510 AVYAHHPRTADEIPMEPGDIIGV---AGNHWdgySKGINRKLGKTGLYPSYKVKE 561
Cdd:cd11801     4 ALHKFIPRHEDEIELDIGDPVYVeqeADDLW---CEGTNLRTGQRGIFPAAYVVE 55

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 2163344826 510 AVYAHHPRTADEIPMEPGDIIGVAGNH-----WDGYSKGinrklGKTGLYP 555
Cdd:cd11836     4 ALYAFEARNPDEISFQPGDIIQVDESQvaepgWLAGELK-----GKTGWFP 49

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2163344826 510 AVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGinRKLGKTGLYPSYKVKE 561
Cdd:cd11874     4 VLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEG--KLNGKVGVFPSNFVKE 53

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 2163344826 509 IAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYP 555
Cdd:cd11925     4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSLRTGVSGVFP 50

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2163344826 510 AVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRklGKTGLYPSYKVKE 561
Cdd:cd11823     4 ALYSYTANREDELSLQPGDIIEVHEKQDDGWWLGELN--GKKGIFPATYVEE 53

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 2163344826 516 PRTADEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPS 556
Cdd:cd11785    10 PQSEAELELKEGDIVFVHKKREDGWFKGTLQRTGKTGLFPG 50

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 2163344826 510 AVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYP 555
Cdd:cd11918     6 AVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGVSRRTQKFGTFP 51

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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2163344826 509 IAVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVKE 561
Cdd:cd11793     3 QCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLRDGERGWFPSSYTEE 55

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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 2163344826 510 AVYAHHPRTADEIPMEPGDIIG-VAGNHWDGYSKgINRKLGKTGLYPS 556
Cdd:cd11777     4 ALYAFVGSSEGTISMTEGEKLSlVEEDKGDGWTR-VRRDTGEEGYVPT 50

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 2163344826 510 AVYAHHPRTADEIPMEPGDIIGVAGNHWDGYSKGINRKLGKTGLYPSYKVK 560
Cdd:cd11917     9 ALYNYMPRNEDELELREGDVIDVMEKCDDGWFVGTSRRTKFFGTFPGNYVK 59