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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 110347457  280 GKACEDVDECAAGLAQCAHGCLNTQGSFKCVCHAGYELGADGR 322
Cdd:cd01475   181 GKICVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDNK 223

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 110347457  410 CEDVDECASSRGGCEHHCTNLAGSFQCSCEAGYRLHEDRR 449
Cdd:cd01475   184 CVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDNK 223

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 110347457   206 CALGNGGCQHHCVqLTITRHRCQCRPGFQLQEDGRHC 242
Cdd:pfam14670    1 CSVNNGGCSHLCL-NTPGGYTCSCPEGYELQDDGRTC 36

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 110347457  280 GKACEDVDECAAGLAQCAHGCLNTQGSFKCVCHAGYELGADGR 322
Cdd:cd01475   181 GKICVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDNK 223

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 110347457   335 CEANNGGCSHGCSHTSAGPLCTCPRGYELDTDQRTC 370
Cdd:pfam14670    1 CSVNNGGCSHLCLNTPGGYTCSCPEGYELQDDGRTC 36

EMI domain; The Pfam alignment is truncated at the C-terminus and does not include the final cysteine defined in Callebaut et al. This is to stop the family overlapping with other domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 110347457    45 PHVCA--EQELTLVGRRQPCVQALSHTVPVWkagCGWQAWCVghERRTVYYMGYRQVYTTEARTVLRCCRGW 114
Cdd:pfam07546    1 RNVCAykVVSCVVVTGTESYVQPVYKPYLTW---CAGHRRCS--TYRTTYRPAYRQVYKTVTRLEWRCCPGW 67

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 110347457   206 CALGNGGCQHHCVqLTITRHRCQCRPGFQLQEDGRHC 242
Cdd:pfam14670    1 CSVNNGGCSHLCL-NTPGGYTCSCPEGYELQDDGRTC 36

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 110347457  280 GKACEDVDECAAGLAQCAHGCLNTQGSFKCVCHAGYELGADGR 322
Cdd:cd01475   181 GKICVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDNK 223

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 110347457   335 CEANNGGCSHGCSHTSAGPLCTCPRGYELDTDQRTC 370
Cdd:pfam14670    1 CSVNNGGCSHLCLNTPGGYTCSCPEGYELQDDGRTC 36

EMI domain; The Pfam alignment is truncated at the C-terminus and does not include the final cysteine defined in Callebaut et al. This is to stop the family overlapping with other domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 110347457    45 PHVCA--EQELTLVGRRQPCVQALSHTVPVWkagCGWQAWCVghERRTVYYMGYRQVYTTEARTVLRCCRGW 114
Cdd:pfam07546    1 RNVCAykVVSCVVVTGTESYVQPVYKPYLTW---CAGHRRCS--TYRTTYRPAYRQVYKTVTRLEWRCCPGW 67

Coagulation Factor Xa inhibitory site; This short domain on coagulation enzyme factor Xa is found to be the target for a potent inhibitor of coagulation, TAK-442.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 110347457   206 CALGNGGCQHHCVqLTITRHRCQCRPGFQLQEDGRHC 242
Cdd:pfam14670    1 CSVNNGGCSHLCL-NTPGGYTCSCPEGYELQDDGRTC 36

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 110347457  161 DVDECRTHNG-GCQHRCVNTPGSYLCECKPGFRLHT 195
Cdd:cd00054     1 DIDECASGNPcQNGGTCVNTVGSYRCSCPPGYTGRN 36