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 30410726    68 RIPEGPIDQGPAIGRVRVLEEQLVKAKEQIENYKKQTRNGLGKDHEILRRRIENGAKELWFFLQSELKKLKNLEGNE-LQ 146
Cdd:pfam19745   1 RLRRSEESKGIANGRLDSLEDQLVKAKQQIEDYKPSAANGPSLEHEVLRRRLENGIQELWYYLSSELKKLRKEIDREsLA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   147 RHADEFLLDLGHHERSIMTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLHH 226
Cdd:pfam19745  81 NHINEILDLLAEHKRSLIADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   227 VVYCFMIAYGTQRTLILESQNWRYATGGWETVFRPVSETCTDRSGISTGHWSGEvKDKNVQVVELPIVDSLHPRPPYLPL 306
Cdd:pfam19745 161 VTYCFIVAYATNRTLILDSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   307 AVPEDLADRLVRVHGDPAVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHV 386
Cdd:pfam19745 240 AIPADLAPRLLKLHGNPPVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWV 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   387 EEHFQLLARRMQVDKKRVYLATDDPSLLKEAKTKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCT 466
Cdd:pfam19745 320 EEYFQQLERRTRVDKRRVYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCT 399

                         410       420       430
                  ....*....|....*....|....*....|..
gi 30410726   467 FSSQVCRVAYEIMQTLHPDASANFHSLDDIYY 498
Cdd:pfam19745 400 FSSQVCRVAYELMQTRYPDASDRFHSLDDIYY 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 30410726    68 RIPEGPIDQGPAIGRVRVLEEQLVKAKEQIENYKKQTRNGLGKDHEILRRRIENGAKELWFFLQSELKKLKNLEGNE-LQ 146
Cdd:pfam19745   1 RLRRSEESKGIANGRLDSLEDQLVKAKQQIEDYKPSAANGPSLEHEVLRRRLENGIQELWYYLSSELKKLRKEIDREsLA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   147 RHADEFLLDLGHHERSIMTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLHH 226
Cdd:pfam19745  81 NHINEILDLLAEHKRSLIADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   227 VVYCFMIAYGTQRTLILESQNWRYATGGWETVFRPVSETCTDRSGISTGHWSGEvKDKNVQVVELPIVDSLHPRPPYLPL 306
Cdd:pfam19745 161 VTYCFIVAYATNRTLILDSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   307 AVPEDLADRLVRVHGDPAVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHV 386
Cdd:pfam19745 240 AIPADLAPRLLKLHGNPPVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWV 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   387 EEHFQLLARRMQVDKKRVYLATDDPSLLKEAKTKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCT 466
Cdd:pfam19745 320 EEYFQQLERRTRVDKRRVYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCT 399

                         410       420       430
                  ....*....|....*....|....*....|..
gi 30410726   467 FSSQVCRVAYEIMQTLHPDASANFHSLDDIYY 498
Cdd:pfam19745 400 FSSQVCRVAYELMQTRYPDASDRFHSLDDIYY 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 30410726 506 NQIAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYPSYKVRE 560
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 30410726    508 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKlGRTGLYPSYKVR 559
Cdd:smart00326   6 RALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGR-GKEGLFPSNYVE 56

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   40 SRELSKILAKLERLKQQNEDLRRMAESLripEGPIDQGPAIGRVRVLEEQLVKAKEQIENYKKQTRNGLGKDHEILRRRI 119
Cdd:PRK03918 458 TAELKRIEKELKEIEEKERKLRKELREL---EKVLKKESELIKLKELAEQLKELEEKLKKYNLEELEKKAEEYEKLKEKL 534

                         90       100
                 ....*....|....*....|...
gi 30410726  120 ENGAKELwFFLQSELKKLKNLEG 142
Cdd:PRK03918 535 IKLKGEI-KSLKKELEKLEELKK 556

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 30410726    68 RIPEGPIDQGPAIGRVRVLEEQLVKAKEQIENYKKQTRNGLGKDHEILRRRIENGAKELWFFLQSELKKLKNLEGNE-LQ 146
Cdd:pfam19745   1 RLRRSEESKGIANGRLDSLEDQLVKAKQQIEDYKPSAANGPSLEHEVLRRRLENGIQELWYYLSSELKKLRKEIDREsLA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   147 RHADEFLLDLGHHERSIMTDLYYLSQTDGAGDWREKEAKDLTELVQRRITYLQNPKDCSKAKKLVCNINKGCGYGCQLHH 226
Cdd:pfam19745  81 NHINEILDLLAEHKRSLIADIEKLSKADGAEEWRKKELKDLSDLVQKRLDHLQNPEDCSKARKLICNLNKGCGFGCQLHH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   227 VVYCFMIAYGTQRTLILESQNWRYATGGWETVFRPVSETCTDRSGISTGHWSGEvKDKNVQVVELPIVDSLHPRPPYLPL 306
Cdd:pfam19745 161 VTYCFIVAYATNRTLILDSKGWRYSKGGWESVFKPLSDTCTERSGAGASPWPGE-ENSDAQVVELPIVDSLNPRPPYLPL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   307 AVPEDLADRLVRVHGDPAVWWVSQFVKYLIRPQPWLEKEIEEATKKLGFKHPVIGVHVRRTDKVGTEAAFHPIEEYMVHV 386
Cdd:pfam19745 240 AIPADLAPRLLKLHGNPPVWWVGQFLKYLMRPQASTQKFLEEAIEKLGFKKPIVGVHVRRTDKVGTEAAFHSIEEYMVWV 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   387 EEHFQLLARRMQVDKKRVYLATDDPSLLKEAKTKYPNYEFISDNSISWSAGLHNRYTENSLRGVILDIHFLSQADFLVCT 466
Cdd:pfam19745 320 EEYFQQLERRTRVDKRRVYLATDDPKVIDEAKTKYPNYEVIGDPKIAKSAGLSSRYTDSSLRGIILDIHLLSLSDYLVCT 399

                         410       420       430
                  ....*....|....*....|....*....|..
gi 30410726   467 FSSQVCRVAYEIMQTLHPDASANFHSLDDIYY 498
Cdd:pfam19745 400 FSSQVCRVAYELMQTRYPDASDRFHSLDDIYY 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 30410726 506 NQIAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYPSYKVRE 560
Cdd:cd11792   1 NQVAIYPHKPRNHDEIELRVGDIIGVAGNHWDGYSKGRNRRTGKTGLYPSYKVKD 55

Variant SH3 domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 30410726   509 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRklGRTGLYPSYKVR 559
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 30410726    508 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKlGRTGLYPSYKVR 559
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 30410726 508 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKlGRTGLYPS 555
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 30410726 508 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 554
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 30410726 508 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 554
Cdd:cd11925   4 LALYAYKPQKNDELELRKGEMYRVIEKCQDGWFKGTSLRTGVSGVFP 50

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 30410726 509 AIYAHQPRTADEIPMEPGDIIGVA----GNHWDGYSKGVNRKLGRTGLYP 554
Cdd:cd11791   4 VLYPYTPQEEDELELVPGDYIYVSpeelDSSSDGWVEGTSWLTGCSGLLP 53

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 30410726 509 AIYAHQPRTADEIPMEPGDIIGVAGNH-----WDGYSKGvnrklGRTGLYP 554
Cdd:cd11836   4 ALYAFEARNPDEISFQPGDIIQVDESQvaepgWLAGELK-----GKTGWFP 49

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 30410726 509 AIYAHQPRTADEIPMEPGDIIG-VAGNHWDGYSKgVNRKLGRTGLYPSYKVR 559
Cdd:cd11777   4 ALYAFVGSSEGTISMTEGEKLSlVEEDKGDGWTR-VRRDTGEEGYVPTSYIR 54

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 30410726 508 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYPSYKVRE 560
Cdd:cd11793   3 QCVHAYTAQQPDELTLEEGDVVNVLRKMPDGWYEGERLRDGERGWFPSSYTEE 55

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 30410726 508 IAIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 554
Cdd:cd11926   3 VAIYPYTPRKEDELELRKGEMFLVFERCQDGWFKGTSMHTSKIGVFP 49

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
                ....*....|....*....|....*....|....*....|....*....|
gi 30410726 508 IAIYAHQPRTADEIPMEPGDIIGVAGN---HWDGYSKGVNRKLGRTGLYP 554
Cdd:cd11886   3 IVIHDFNARSEDELTLKPGDKIELIEDdeeFGDGWYLGRNLRTGETGLFP 52

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 30410726 509 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGvnRKLGRTGLYPS 555
Cdd:cd11827   4 ALYAYDAQDTDELSFNEGDIIEILKEDPSGWWTG--RLRGKEGLFPG 48

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 30410726 509 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGVNRKLGRTGLYP 554
Cdd:cd11918   6 AVYQYRPQNEDELELREGDRVDVMQQCDDGWFVGVSRRTQKFGTFP 51

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726   40 SRELSKILAKLERLKQQNEDLRRMAESLripEGPIDQGPAIGRVRVLEEQLVKAKEQIENYKKQTRNGLGKDHEILRRRI 119
Cdd:PRK03918 458 TAELKRIEKELKEIEEKERKLRKELREL---EKVLKKESELIKLKELAEQLKELEEKLKKYNLEELEKKAEEYEKLKEKL 534

                         90       100
                 ....*....|....*....|...
gi 30410726  120 ENGAKELwFFLQSELKKLKNLEG 142
Cdd:PRK03918 535 IKLKGEI-KSLKKELEKLEELKK 556

Alpha-1,2-fucosyltransferase; Alpha-1,2-fucosyltransferases (Fut1, Fut2) catalyze the transfer of alpha-L-fucose to the terminal beta-D-galactose residue of glycoconjugates via an alpha-1,2-linkage, generating carbohydrate structures that exhibit H-antigenicity for blood-group carbohydrates. These structures also act as ligands for morphogenesis, the adhesion of microbes, and metastasizing cancer cells. Fut1 is responsible for producing the H antigen on red blood cells. Fut2 is expressed in epithelia of secretory tissues, and individuals termed "secretors" have at least one functional copy of the gene; they secrete H antigen which is further processed into A and/or B antigens depending on the ABO genotype. O-fucosyltransferase-like proteins are GDP-fucose dependent enzymes with similarities to the family 1 glycosyltransferases (GT1). They are soluble ER proteins that may be proteolytically cleaved from a membrane-associated preprotein, and are involved in the O-fucosylation of protein substrates, the core fucosylation of growth factor receptors, and other processes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30410726 342 LEKEIEEATKKLGFKH---PVIGVHVRRTD--KVGTEAAFHPI--EEYMVHVEEHFQLLarrmqVDKKRVYLATDDPSLL 414
Cdd:cd11301 118 LEEENNKILKKLKEELkntNSVSVHIRRGDylTNGNAKGYHGIcdLEYYKKAIEYIKEK-----VKNPVFFVFSDDIEWV 192

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 30410726 415 KE--AKTKYPNYEFISDNSiswsaglhnrytenslrGVILDIHFLSQADFLVC---TFS 468
Cdd:cd11301 193 KEnlALTSKENVYFVDGNN-----------------SSYEDLYLMSLCKHVIIsnsTFS 234

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 30410726 509 AIYAHQPRTADEIPMEPGDIIGVAGNHWDGYSKGvnRKLGRTGLYPSYKVRE 560
Cdd:cd11874   4 VLFSYTPQNEDELELKVGDTIEVLGEVEEGWWEG--KLNGKVGVFPSNFVKE 53