Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 56693245   120 DVDECERDSHDCQPSQQCFNTEGSFSCQCPDG 151
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRCPDG 32

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 56693245 195 NRSCIDVDECGMGAP-CSQWCYNTYGTFLCRCEQGYELGPDG 235
Cdd:cd01475 181 GKICVVPDLCATLSHvCQQVCISTPGSYLCACTEGYALLEDN 222

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 56693245    240 DIDECSySSYLCQY--QCVNEHGKFSCVCPEGYQ 271
Cdd:smart00179   1 DIDECA-SGNPCQNggTCVNTVGSYRCECPPGYT 33

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 56693245   120 DVDECERDSHDCQPSQQCFNTEGSFSCQCPDG 151
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRCPDG 32

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 56693245 120 DVDECErDSHDCQPSQQCFNTEGSFSCQCPDGYRkvGTECI 160
Cdd:cd00054   1 DIDECA-SGNPCQNGGTCVNTVGSYRCSCPPGYT--GRNCE 38

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 56693245 195 NRSCIDVDECGMGAP-CSQWCYNTYGTFLCRCEQGYELGPDG 235
Cdd:cd01475 181 GKICVVPDLCATLSHvCQQVCISTPGSYLCACTEGYALLEDN 222

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*...
gi 56693245   280 DINECETGAHQCSDGQTCVNIHGGHKCV 307
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECR 28

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 56693245 161 DIDECR-YRYCQH--RCVNVPGSFSCQCEPGFQL 191
Cdd:cd00054   1 DIDECAsGNPCQNggTCVNTVGSYRCSCPPGYTG 34

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 56693245    240 DIDECSySSYLCQY--QCVNEHGKFSCVCPEGYQ 271
Cdd:smart00179   1 DIDECA-SGNPCQNggTCVNTVGSYRCECPPGYT 33

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 56693245   120 DVDECERDSHDCQPSQQCFNTEGSFSCQCPDG 151
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRCPDG 32

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 56693245 120 DVDECErDSHDCQPSQQCFNTEGSFSCQCPDGYRkvGTECI 160
Cdd:cd00054   1 DIDECA-SGNPCQNGGTCVNTVGSYRCSCPPGYT--GRNCE 38

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
                  ....*....|....*....|....*....
gi 56693245   170 CQHRCVNVPGSFSCQCEPGFQLAGNNRSC 198
Cdd:pfam14670   8 CSHLCLNTPGGYTCSCPEGYELQDDGRTC 36

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|...
gi 56693245    161 DIDEC-RYRYCQH--RCVNVPGSFSCQCEPGFQ 190
Cdd:smart00179   1 DIDECaSGNPCQNggTCVNTVGSYRCECPPGYT 33

Calcium-binding EGF domain;

                          10        20
                  ....*....|....*....|....*...
gi 56693245   280 DINECETGAHQCSDGQTCVNIHGGHKCV 307
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECR 28

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 56693245   182 SCQCEPGFQLAGNNRSCIDVDE 203
Cdd:pfam12662   1 TCSCPPGYQLDPDGRTCVDIDE 22

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 56693245 159 CIDIDECRY--RYCQHRCVNVPGSFSCQCEPGFQLAGNNRS 197
Cdd:cd01475 184 CVVPDLCATlsHVCQQVCISTPGSYLCACTEGYALLEDNKT 224

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|..
gi 56693245   200 DVDECGMGA---PCSQWCYNTYGTFLCRCEQG 228
Cdd:pfam07645   1 DVDECATGThncPANTVCVNTIGSFECRCPDG 32

Epidermal growth factor domain, found in epidermal growth factor (EGF) presents in a large number of proteins, mostly animal; the list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied; the functional significance of EGF-like domains in what appear to be unrelated proteins is not yet clear; a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase); the domain includes six cysteine residues which have been shown to be involved in disulfide bonds; the main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet; Subdomains between the conserved cysteines vary in length; the region between the 5th and 6th cysteine contains two conserved glycines of which at least one is present in most EGF-like domains; a subset of these bind calcium.

                        10        20        30
                ....*....|....*....|....*....|.
gi 56693245 123 ECErDSHDCQPSQQCFNTEGSFSCQCPDGYR 153
Cdd:cd00053   1 ECA-ASNPCSNGGTCVNTPGSYRCVCPPGYT 30