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 808356696 386 GFCEDVNECTTGIAACEQKCVNIPGSYQCICDRGFALGPDG 426
Cdd:cd01475  182 KICVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDN 222

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 808356696   431 DIDECSIWAGSGNDlcmGGCINTKGSYLCQCPPGYKiqpDGRTCV 475
Cdd:smart00179   1 DIDECASGNPCQNG---GTCVNTVGSYRCECPPGYT---DGRNCE 39

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 808356696 386 GFCEDVNECTTGIAACEQKCVNIPGSYQCICDRGFALGPDG 426
Cdd:cd01475  182 KICVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDN 222

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 808356696 343 DIDECVTGHNCGAGEECVNTPGSFRCQqkgnlCAHGYE 380
Cdd:cd00054    1 DIDECASGNPCQNGGTCVNTVGSYRCS-----CPPGYT 33

Complement Clr-like EGF-like; cEGF, or complement Clr-like EGF, domains have six conserved cysteine residues disulfide-bonded into the characteriztic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL receptor. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal cysteine residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In cEGFs the C-terminal thiol resides on the C-terminal beta-sheet, resulting in long loop-lengths between the cysteine residues of disulfide 'c', typically C[10+]XC. These longer loop-lengths may have arisen by selective cysteine loss from a four-disulfide EGF template such as laminin or integrin. Tandem cEGF domains have five linking residues between terminal cysteines of adjacent domains. cEGF domains may or may not bind calcium in the linker region. cEGF domains with the consensus motif CXN4X[F,Y]XCXC are hydroxylated exclusively on the asparagine residue.

                          10        20
                  ....*....|....*....|.
gi 808356696  459 CQCPPGYKIQPDGRTCVDVDE 479
Cdd:pfam12662   2 CSCPPGYQLDPDGRTCVDIDE 22

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        40
                 ....*....|....*....|....*....|....*....|....*..
gi 808356696 431 DIDECSIwagsgNDLCMGG--CINTKGSYLCQCPPGYKiqpdGRTCV 475
Cdd:cd00054    1 DIDECAS-----GNPCQNGgtCVNTVGSYRCSCPPGYT----GRNCE 38

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 808356696   390 DVNECTTGiAACEQ--KCVNIPGSYQCICDRGFAlgpDGTKCE 430
Cdd:smart00179   1 DIDECASG-NPCQNggTCVNTVGSYRCECPPGYT---DGRNCE 39

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 808356696 386 GFCEDVNECTTGIAACEQKCVNIPGSYQCICDRGFALGPDG 426
Cdd:cd01475  182 KICVVPDLCATLSHVCQQVCISTPGSYLCACTEGYALLEDN 222

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 808356696 343 DIDECVTGHNCGAGEECVNTPGSFRCQqkgnlCAHGYE 380
Cdd:cd00054    1 DIDECASGNPCQNGGTCVNTVGSYRCS-----CPPGYT 33

Complement Clr-like EGF-like; cEGF, or complement Clr-like EGF, domains have six conserved cysteine residues disulfide-bonded into the characteriztic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL receptor. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal cysteine residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In cEGFs the C-terminal thiol resides on the C-terminal beta-sheet, resulting in long loop-lengths between the cysteine residues of disulfide 'c', typically C[10+]XC. These longer loop-lengths may have arisen by selective cysteine loss from a four-disulfide EGF template such as laminin or integrin. Tandem cEGF domains have five linking residues between terminal cysteines of adjacent domains. cEGF domains may or may not bind calcium in the linker region. cEGF domains with the consensus motif CXN4X[F,Y]XCXC are hydroxylated exclusively on the asparagine residue.

                          10        20
                  ....*....|....*....|.
gi 808356696  459 CQCPPGYKIQPDGRTCVDVDE 479
Cdd:pfam12662   2 CSCPPGYQLDPDGRTCVDIDE 22

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 808356696  443 NDLCMGGCINTKGSYLCQCPPGYKIQPDGRTC 474
Cdd:pfam14670   5 NGGCSHLCLNTPGGYTCSCPEGYELQDDGRTC 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 808356696 429 CEDIDECSiwagSGNDLCMGGCINTKGSYLCQCPPGYKIQPDGRT 473
Cdd:cd01475  184 CVVPDLCA----TLSHVCQQVCISTPGSYLCACTEGYALLEDNKT 224

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 808356696   390 DVNECTTGiAACEQ--KCVNIPGSYQCICDRGFAlgpDGTKCE 430
Cdd:smart00179   1 DIDECASG-NPCQNggTCVNTVGSYRCECPPGYT---DGRNCE 39

Complement Clr-like EGF-like; cEGF, or complement Clr-like EGF, domains have six conserved cysteine residues disulfide-bonded into the characteriztic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL receptor. The core fold of the EGF domain consists of two small beta-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal cysteine residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In cEGFs the C-terminal thiol resides on the C-terminal beta-sheet, resulting in long loop-lengths between the cysteine residues of disulfide 'c', typically C[10+]XC. These longer loop-lengths may have arisen by selective cysteine loss from a four-disulfide EGF template such as laminin or integrin. Tandem cEGF domains have five linking residues between terminal cysteines of adjacent domains. cEGF domains may or may not bind calcium in the linker region. cEGF domains with the consensus motif CXN4X[F,Y]XCXC are hydroxylated exclusively on the asparagine residue.

                          10        20
                  ....*....|....*....|..
gi 808356696  413 QCICDRGFALGPDGTKCEDIDE 434
Cdd:pfam12662   1 TCSCPPGYQLDPDGRTCVDIDE 22