Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 569004040    65 DIDECATSNTTLCAHICINTMGSYHCECREGYIledDGRTCT 106
Cdd:smart00179   1 DIDECASGNPCQNGGTCVNTVGSYRCECPPGYT---DGRNCE 39

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 569004040    65 DIDECATSNTTLCAHICINTMGSYHCECREGYIledDGRTCT 106
Cdd:smart00179   1 DIDECASGNPCQNGGTCVNTVGSYRCECPPGYT---DGRNCE 39

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 569004040  65 DIDECATSNTTLCAHICINTMGSYHCECREGYIleddGRTCT 106
Cdd:cd00054    1 DIDECASGNPCQNGGTCVNTVGSYRCSCPPGYT----GRNCE 38

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 569004040    65 DIDECATSNTTLCAHICINTMGSYHCECREGYIledDGRTCT 106
Cdd:smart00179   1 DIDECASGNPCQNGGTCVNTVGSYRCECPPGYT---DGRNCE 39

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 569004040  65 DIDECATSNTTLCAHICINTMGSYHCECREGYIleddGRTCT 106
Cdd:cd00054    1 DIDECASGNPCQNGGTCVNTVGSYRCSCPPGYT----GRNCE 38

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|...
gi 569004040   65 DIDECATSnTTLCAH--ICINTMGSYHCECREG 95
Cdd:pfam07645   1 DVDECATG-THNCPAntVCVNTIGSFECRCPDG 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 569004040  68 ECATSNTTLCAHICINTMGSYHCECREGYILEddgRTCT 106
Cdd:cd00053    1 ECAASNPCSNGGTCVNTPGSYRCVCPPGYTGD---RSCE 36

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
                  ....*....|....*...
gi 569004040   89 HCECREGYILEDDGRTCT 106
Cdd:pfam12662   1 TCSCPPGYQLDPDGRTCV 18