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 17533685  13 ATTQASTDRNCGSNWNNLWLDIVIVVDNSKGMTNEGITEVAANIATTFASGPRIGTDYSDPRSTRLSILTYNSEATVVAD 92
Cdd:cd01477   1 SPAAAYTDRECGSDIKNLWLDIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIGTDYDDPRSTRVGLVTYNSNATVVAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533685  93 LNQFQSADDVYQTLFSFLNEVSDSDDSFLAKGLGMAESVLYNGrMNGVRENYNRLVVVYASAYREDG-EDPLNIAKRLRS 171
Cdd:cd01477  81 LNDLQSFDDLYSQIQGSLTDVSSTNASYLDTGLQAAEQMLAAG-KRTSRENYKKVVIVFASDYNDEGsNDPRPIAARLKS 159

                       170       180       190
                ....*....|....*....|....*....|....
gi 17533685 172 SGVAIATVAFDPDGDGLLLSKLSKIASPNMSFKS 205
Cdd:cd01477 160 TGIAIITVAFTQDESSNLLDKLGKIASPGMNFTS 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 17533685  13 ATTQASTDRNCGSNWNNLWLDIVIVVDNSKGMTNEGITEVAANIATTFASGPRIGTDYSDPRSTRLSILTYNSEATVVAD 92
Cdd:cd01477   1 SPAAAYTDRECGSDIKNLWLDIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIGTDYDDPRSTRVGLVTYNSNATVVAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533685  93 LNQFQSADDVYQTLFSFLNEVSDSDDSFLAKGLGMAESVLYNGrMNGVRENYNRLVVVYASAYREDG-EDPLNIAKRLRS 171
Cdd:cd01477  81 LNDLQSFDDLYSQIQGSLTDVSSTNASYLDTGLQAAEQMLAAG-KRTSRENYKKVVIVFASDYNDEGsNDPRPIAARLKS 159

                       170       180       190
                ....*....|....*....|....*....|....
gi 17533685 172 SGVAIATVAFDPDGDGLLLSKLSKIASPNMSFKS 205
Cdd:cd01477 160 TGIAIITVAFTQDESSNLLDKLGKIASPGMNFTS 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 17533685     33 DIVIVVDNSKGMTNEGITEVAANIATTfasgprIGTDYSDPRSTRLSILTYNSEATVVADLNQFQSADDVYQTLFSFlnE 112
Cdd:smart00327   1 DVVFLLDGSGSMGGNRFELAKEFVLKL------VEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASL--S 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533685    113 VSDSDDSFLAKGLGMAESVLYNgRMNGVRENYNRLVVVYASAYREDG-EDPLNIAKRLRSSGVAIATVAFDPDGDgllLS 191
Cdd:smart00327  73 YKLGGGTNLGAALQYALENLFS-KSAGSRRGAPKVVILITDGESNDGpKDLLKAAKELKRSGVKVFVVGVGNDVD---EE 148

                          170       180
                   ....*....|....*....|....
gi 17533685    192 KLSKIASPNMSFKSRDPNLVGKIQ 215
Cdd:smart00327 149 ELKKLASAPGGVYVFLPELLDLLI 172

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 17533685 247 CIRAETITASWASAKIACQNsiKYGYLVTEFDDRKHDFLFRIALNNaeftEPYAYHTGLSYV--NGAWRWQQpeGHPLIl 324
Cdd:cd00037   2 CYKFSTEKLTWEEAQEYCRS--LGGHLASIHSEEENDFLASLLKKS----SSSDVWIGLNDLssEGTWKWSD--GSPLV- 72

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 17533685 325 qngSYSHWNPTYPNTPFT-NTVVVNHQHNSnldvGWQNINGYRENeNYMCEV 375
Cdd:cd00037  73 ---DYTNWAPGEPNPGGSeDCVVLSSSSDG----KWNDVSCSSKL-PFICEK 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 17533685  13 ATTQASTDRNCGSNWNNLWLDIVIVVDNSKGMTNEGITEVAANIATTFASGPRIGTDYSDPRSTRLSILTYNSEATVVAD 92
Cdd:cd01477   1 SPAAAYTDRECGSDIKNLWLDIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIGTDYDDPRSTRVGLVTYNSNATVVAD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533685  93 LNQFQSADDVYQTLFSFLNEVSDSDDSFLAKGLGMAESVLYNGrMNGVRENYNRLVVVYASAYREDG-EDPLNIAKRLRS 171
Cdd:cd01477  81 LNDLQSFDDLYSQIQGSLTDVSSTNASYLDTGLQAAEQMLAAG-KRTSRENYKKVVIVFASDYNDEGsNDPRPIAARLKS 159

                       170       180       190
                ....*....|....*....|....*....|....
gi 17533685 172 SGVAIATVAFDPDGDGLLLSKLSKIASPNMSFKS 205
Cdd:cd01477 160 TGIAIITVAFTQDESSNLLDKLGKIASPGMNFTS 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 17533685     33 DIVIVVDNSKGMTNEGITEVAANIATTfasgprIGTDYSDPRSTRLSILTYNSEATVVADLNQFQSADDVYQTLFSFlnE 112
Cdd:smart00327   1 DVVFLLDGSGSMGGNRFELAKEFVLKL------VEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASL--S 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533685    113 VSDSDDSFLAKGLGMAESVLYNgRMNGVRENYNRLVVVYASAYREDG-EDPLNIAKRLRSSGVAIATVAFDPDGDgllLS 191
Cdd:smart00327  73 YKLGGGTNLGAALQYALENLFS-KSAGSRRGAPKVVILITDGESNDGpKDLLKAAKELKRSGVKVFVVGVGNDVD---EE 148

                          170       180
                   ....*....|....*....|....
gi 17533685    192 KLSKIASPNMSFKSRDPNLVGKIQ 215
Cdd:smart00327 149 ELKKLASAPGGVYVFLPELLDLLI 172

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 17533685    225 CPRTWIQYRpsyddeksykfGICIRAETITASWASAKIACQNsiKYGYLVTEFDDRKHDFLFRIALNNAEFTEpyaYHTG 304
Cdd:smart00034   1 CPSGWISYG-----------GKCYKFSTEKKTWEDAQAFCQS--LGGHLASIHSEAENDFVASLLKNSGSSDY---YWIG 64

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17533685    305 LSY--VNGAWRWQQPEGhplilqNGSYSHWNPTYPNTPFTNTVVVNHqhnsnLDVGWQNINGYRENeNYMCE 374
Cdd:smart00034  65 LSDpdSNGSWQWSDGSG------PVSYSNWAPGEPNNSSGDCVVLST-----SGGKWNDVSCTSKL-PFVCE 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 17533685 247 CIRAETITASWASAKIACQNsiKYGYLVTEFDDRKHDFLFRIALNNaeftEPYAYHTGLSYV--NGAWRWQQpeGHPLIl 324
Cdd:cd00037   2 CYKFSTEKLTWEEAQEYCRS--LGGHLASIHSEEENDFLASLLKKS----SSSDVWIGLNDLssEGTWKWSD--GSPLV- 72

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 17533685 325 qngSYSHWNPTYPNTPFT-NTVVVNHQHNSnldvGWQNINGYRENeNYMCEV 375
Cdd:cd00037  73 ---DYTNWAPGEPNPGGSeDCVVLSSSSDG----KWNDVSCSSKL-PFICEK 116

von Willebrand factor type A domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533685    34 IVIVVDNSKGMTNEGIT----EVAANIATTFASgpRIGTDysdprstRLSILTYNSEATVVADLNqfqsadDVYQTLFSF 109
Cdd:pfam13519   1 LVFVLDTSGSMRNGDYGptrlEAAKDAVLALLK--SLPGD-------RVGLVTFGDGPEVLIPLT------KDRAKILRA 65

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 17533685   110 LNEVSD-SDDSFLAKGLGMAESVLyngrmNGVRENYNRLVVV 150
Cdd:pfam13519  66 LRRLEPkGGGTNLAAALQLARAAL-----KHRRKNQPRRIVL 102

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533685  76 TRLSILTYNSEATVVADLNQFQSAddVYQTLFSfLNEVSDSDDSFLAKGLGMAESVLYNGRMNGVRENYnrlvVVYASAy 155
Cdd:cd01474  40 LRFSFITFSTRATKILPLTDDSSA--IIKGLEV-LKKVTPSGQTYIHEGLENANEQIFNRNGGGRETVS----VIIALT- 111

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17533685 156 reDGEDPLNI-------AKRLRSSGVAIATVAFdpdgDGLLLSKLSKIAS 198
Cdd:cd01474 112 --DGQLLLNGhkypeheAKLSRKLGAIVYCVGV----TDFLKSQLINIAD 155