VWA F09G8.8 type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. The members of this subgroup lack the MIDAS motif. This subgroup is found only in C. elegans and the members identified thus far are always found fused to a C-Lectin type domain. Biochemical function thus far has not be attributed to any of the members of this subgroup.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915  22 QNAAAYTDPACPGNIKNLWLDVVVVVDRSMQMTDAQLWQVRQTLTQVFGSDIRIGTGYSDKRSTCVGFVTYNSNATVTAE 101
Cdd:cd01477   1 SPAAAYTDRECGSDIKNLWLDIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIGTDYDDPRSTRVGLVTYNSNATVVAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915 102 LDIAKSFPDIYNIIQGSLVDVASTNASSLGEGLLAAQRVLNSGrQRTNRYNVKQVILAFAADFQDEFSNlNAIELSRDLQ 181
Cdd:cd01477  81 LNDLQSFDDLYSQIQGSLTDVSSTNASYLDTGLQAAEQMLAAG-KRTSRENYKKVVIVFASDYNDEGSN-DPRPIAARLK 158

                       170       180       190
                ....*....|....*....|....*....|....*
gi 17537915 182 SNGISIITVACTK--DSYALPRINMCATPGYAFVD 214
Cdd:cd01477 159 STGIAIITVAFTQdeSSNLLDKLGKIASPGMNFTS 193

VWA F09G8.8 type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. The members of this subgroup lack the MIDAS motif. This subgroup is found only in C. elegans and the members identified thus far are always found fused to a C-Lectin type domain. Biochemical function thus far has not be attributed to any of the members of this subgroup.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915  22 QNAAAYTDPACPGNIKNLWLDVVVVVDRSMQMTDAQLWQVRQTLTQVFGSDIRIGTGYSDKRSTCVGFVTYNSNATVTAE 101
Cdd:cd01477   1 SPAAAYTDRECGSDIKNLWLDIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIGTDYDDPRSTRVGLVTYNSNATVVAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915 102 LDIAKSFPDIYNIIQGSLVDVASTNASSLGEGLLAAQRVLNSGrQRTNRYNVKQVILAFAADFQDEFSNlNAIELSRDLQ 181
Cdd:cd01477  81 LNDLQSFDDLYSQIQGSLTDVSSTNASYLDTGLQAAEQMLAAG-KRTSRENYKKVVIVFASDYNDEGSN-DPRPIAARLK 158

                       170       180       190
                ....*....|....*....|....*....|....*
gi 17537915 182 SNGISIITVACTK--DSYALPRINMCATPGYAFVD 214
Cdd:cd01477 159 STGIAIITVAFTQdeSSNLLDKLGKIASPGMNFTS 193

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915     49 RSMQMTDAQLWQVRQTLTQVfgsdirIGTGYSDKRSTCVGFVTYNSNATVTAELDIAKSFPDIYNIIQGslVDVASTNAS 128
Cdd:smart00327   8 GSGSMGGNRFELAKEFVLKL------VEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALAS--LSYKLGGGT 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915    129 SLGEGLLAAQRVLNSGRQRtNRYNVKQVILAFaADFQDEFSNLNAIELSRDLQSNGISIITVACTKDSYA--LPRINMCA 206
Cdd:smart00327  80 NLGAALQYALENLFSKSAG-SRRGAPKVVILI-TDGESNDGPKDLLKAAKELKRSGVKVFVVGVGNDVDEeeLKKLASAP 157

                          170
                   ....*....|....*....
gi 17537915    207 TPGYAFVDEmNTSKLVKQL 225
Cdd:smart00327 158 GGVYVFLPE-LLDLLIDLL 175

C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915 254 CIKGFDFSGSawgYDHAVQYCQNQvsRGHLANEFSKEKHDFInlymMNTFNRGMHLDYSIGLRYLNS--TWVWEEpkGQP 331
Cdd:cd00037   2 CYKFSTEKLT---WEEAQEYCRSL--GGHLASIHSEEENDFL----ASLLKKSSSSDVWIGLNDLSSegTWKWSD--GSP 70

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 17537915 332 KLPlnpdiYSTWAPGYPQKNSTGQVVGVKANGILTNWVGSATSEWLFVCQV 382
Cdd:cd00037  71 LVD-----YTNWAPGEPNPGGSEDCVVLSSSSDGKWNDVSCSSKLPFICEK 116

VWA F09G8.8 type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. The members of this subgroup lack the MIDAS motif. This subgroup is found only in C. elegans and the members identified thus far are always found fused to a C-Lectin type domain. Biochemical function thus far has not be attributed to any of the members of this subgroup.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915  22 QNAAAYTDPACPGNIKNLWLDVVVVVDRSMQMTDAQLWQVRQTLTQVFGSDIRIGTGYSDKRSTCVGFVTYNSNATVTAE 101
Cdd:cd01477   1 SPAAAYTDRECGSDIKNLWLDIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIGTDYDDPRSTRVGLVTYNSNATVVAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915 102 LDIAKSFPDIYNIIQGSLVDVASTNASSLGEGLLAAQRVLNSGrQRTNRYNVKQVILAFAADFQDEFSNlNAIELSRDLQ 181
Cdd:cd01477  81 LNDLQSFDDLYSQIQGSLTDVSSTNASYLDTGLQAAEQMLAAG-KRTSRENYKKVVIVFASDYNDEGSN-DPRPIAARLK 158

                       170       180       190
                ....*....|....*....|....*....|....*
gi 17537915 182 SNGISIITVACTK--DSYALPRINMCATPGYAFVD 214
Cdd:cd01477 159 STGIAIITVAFTQdeSSNLLDKLGKIASPGMNFTS 193

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915     49 RSMQMTDAQLWQVRQTLTQVfgsdirIGTGYSDKRSTCVGFVTYNSNATVTAELDIAKSFPDIYNIIQGslVDVASTNAS 128
Cdd:smart00327   8 GSGSMGGNRFELAKEFVLKL------VEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALAS--LSYKLGGGT 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915    129 SLGEGLLAAQRVLNSGRQRtNRYNVKQVILAFaADFQDEFSNLNAIELSRDLQSNGISIITVACTKDSYA--LPRINMCA 206
Cdd:smart00327  80 NLGAALQYALENLFSKSAG-SRRGAPKVVILI-TDGESNDGPKDLLKAAKELKRSGVKVFVVGVGNDVDEeeLKKLASAP 157

                          170
                   ....*....|....*....
gi 17537915    207 TPGYAFVDEmNTSKLVKQL 225
Cdd:smart00327 158 GGVYVFLPE-LLDLLIDLL 175

C-type lectin (CTL) or carbohydrate-recognition domain (CRD); Many of these domains function as calcium-dependent carbohydrate binding modules.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915    236 CPEDWVQYTGSdkkklgvCIKgfdFSGSAWGYDHAVQYCQNQvsRGHLANEFSKEKHDFINLYMMNTFNRGmhlDYSIGL 315
Cdd:smart00034   1 CPSGWISYGGK-------CYK---FSTEKKTWEDAQAFCQSL--GGHLASIHSEAENDFVASLLKNSGSSD---YYWIGL 65

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17537915    316 RYL--NSTWVWEEPKGqpklplnPDIYSTWAPGYPQkNSTGQVVGVKANGILTNWVgSATSEWLFVCQ 381
Cdd:smart00034  66 SDPdsNGSWQWSDGSG-------PVSYSNWAPGEPN-NSSGDCVVLSTSGGKWNDV-SCTSKLPFVCE 124

C-type lectin (CTL)/C-type lectin-like (CTLD) domain; CLECT: C-type lectin (CTL)/C-type lectin-like (CTLD) domain; protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. This group is chiefly comprised of eukaryotic CTLDs, but contains some, as yet functionally uncharacterized, bacterial CTLDs. Many CTLDs are calcium-dependent carbohydrate binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Animal C-type lectins are involved in such functions as extracellular matrix organization, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. For example: mannose-binding lectin and lung surfactant proteins A and D bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, and apoptotic cells) and mediate functions associated with killing and phagocytosis; P (platlet)-, E (endothelial)-, and L (leukocyte)- selectins (sels) mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls enabling subsequent lymphocyte adhesion and transmigration. CTLDs may bind a variety of carbohydrate ligands including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. Several CTLDs bind to protein ligands, and only some of these binding interactions are Ca2+-dependent; including the CTLDs of Coagulation Factors IX/X (IX/X) and Von Willebrand Factor (VWF) binding proteins, and natural killer cell receptors. C-type lectins, such as lithostathine, and some type II antifreeze glycoproteins function in a Ca2+-independent manner to bind inorganic surfaces. Many proteins in this group contain a single CTLD; these CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers, from which ligand-binding sites project in different orientations. Various vertebrate type 1 transmembrane proteins including macrophage mannose receptor, endo180, phospholipase A2 receptor, and dendritic and epithelial cell receptor (DEC205) have extracellular domains containing 8 or more CTLDs; these CTLDs remain in the parent model. In some members (IX/X and VWF binding proteins), a loop extends to the adjoining domain to form a loop-swapped dimer. A similar conformation is seen in the macrophage mannose receptor CRD4's putative non-sugar bound form of the domain in the acid environment of the endosome. Lineage specific expansions of CTLDs have occurred in several animal lineages including Drosophila melanogaster and Caenorhabditis elegans; these CTLDs also remain in the parent model.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915 254 CIKGFDFSGSawgYDHAVQYCQNQvsRGHLANEFSKEKHDFInlymMNTFNRGMHLDYSIGLRYLNS--TWVWEEpkGQP 331
Cdd:cd00037   2 CYKFSTEKLT---WEEAQEYCRSL--GGHLASIHSEEENDFL----ASLLKKSSSSDVWIGLNDLSSegTWKWSD--GSP 70

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 17537915 332 KLPlnpdiYSTWAPGYPQKNSTGQVVGVKANGILTNWVGSATSEWLFVCQV 382
Cdd:cd00037  71 LVD-----YTNWAPGEPNPGGSEDCVVLSSSSDGKWNDVSCSSKLPFICEK 116

C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2); CLECT_REG-1_like: C-type lectin-like domain (CTLD) of the type found in Human REG-1 (lithostathine), REG-4, and avian eggshell-specific proteins: ansocalcin, structhiocalcin-1(SCA-1), and -2(SCA-2). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. REG-1 is a proliferating factor which participates in various kinds of tissue regeneration including pancreatic beta-cell regeneration, regeneration of intestinal mucosa, regeneration of motor neurons, and perhaps in tissue regeneration of damaged heart. REG-1 may play a role on the pathophysiology of Alzheimer's disease and in the development of gastric cancers. Its expression is correlated with reduced survival from early-stage colorectal cancer. REG-1 also binds and aggregates several bacterial strains from the intestinal flora and it has been suggested that it is involved in the control of the intestinal bacterial ecosystem. Rat lithostathine has calcium carbonate crystal inhibitor activity in vitro. REG-IV is unregulated in pancreatic, gastric, hepatocellular, and prostrate adenocarcinomas. REG-IV activates the EGF receptor/Akt/AP-1 signaling pathway in colorectal carcinoma. Ansocalcin, SCA-1 and -2 are found at high concentration in the calcified egg shell layer of goose and ostrich, respectively and tend to form aggregates. Ansocalcin nucleates calcite crystal aggregates in vitro.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17537915 236 CPEDWVQYTGSdkkklgvCIKGFDFSGSaWgyDHAVQYCQNQVSRGHLANEFSKEKHDFINLYMMNTFNRGMhlDYSIGL 315
Cdd:cd03594   1 CPKGWLPYKGN-------CYGYFRQPLS-W--SDAELFCQKYGPGAHLASIHSPAEAAAIASLISSYQKAYQ--PVWIGL 68

                        90
                ....*....|.
gi 17537915 316 RYLN--STWVW 324
Cdd:cd03594  69 HDPQqsRGWEW 79