TB domain; This domain is also known as the 8 cysteine domain. This family includes the hybrid domains. This cysteine rich repeat is found in TGF binding protein and fibrillin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1622855666 1304 CDNVLSPNVTKQECCCTS-GAGWGDNCEifPCPVLGTAEFTEMC 1346
Cdd:pfam00683    3 CSNPLPGNVTKSECCCTSvGRAWGSPCE--LCPPPGTDEFRELC 44

TB domain; This domain is also known as the 8 cysteine domain. This family includes the hybrid domains. This cysteine rich repeat is found in TGF binding protein and fibrillin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1622855666 1480 VCSRPLVGkQTTYTECCCLY-GEAWGMQCALCPMKDSDDYAQLC 1522
Cdd:pfam00683    2 RCSNPLPG-NVTKSECCCTSvGRAWGSPCELCPPPGTDEFRELC 44

Calcium-binding EGF-like domain;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|..
gi 1622855666  1067 DIDECQHHHLCAHG-QCRNTEGSFQCVCDQGYRAsglGDHCE 1107
Cdd:smart00179    1 DIDECASGNPCQNGgTCVNTVGSYRCECPPGYTD---GRNCE 39

Calcium-binding EGF-like domain;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|..
gi 1622855666  1191 DIDECVNNTVCDSHGFCDNTAGSFRCLCYQGFqapQDGQGCV 1232
Cdd:smart00179    1 DIDECASGNPCQNGGTCVNTVGSYRCECPPGY---TDGRNCE 39

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|..
gi 1622855666   627 DINECQLQGVCPNG-ECLNTMGSYRCTCKIGF 657
Cdd:smart00179    1 DIDECASGNPCQNGgTCVNTVGSYRCECPPGY 32

Calcium-binding EGF domain;

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1622855666 1108 DINECLEDKSVCQR-GDCINTAGSYDCTCPDG 1138
Cdd:pfam07645    1 DVDECATGTHNCPAnTVCVNTIGSFECRCPDG 32

Calcium-binding EGF-like domain;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|..
gi 1622855666   904 DVDECLRPDVCGEG-HCVNTVGAFRCEyCDSGYrmTQRGRCE 944
Cdd:smart00179    1 DIDECASGNPCQNGgTCVNTVGSYRCE-CPPGY--TDGRNCE 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
                   ....*....|....*....|....*....|....*
gi 1622855666  945 DIDECLNPSTC-PDEQCVNSPGSYQCVpCTEGFRG 978
Cdd:cd00054      1 DIDECASGNPCqNGGTCVNTVGSYRCS-CPPGYTG 34

TB domain; This domain is also known as the 8 cysteine domain. This family includes the hybrid domains. This cysteine rich repeat is found in TGF binding protein and fibrillin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1622855666 1304 CDNVLSPNVTKQECCCTS-GAGWGDNCEifPCPVLGTAEFTEMC 1346
Cdd:pfam00683    3 CSNPLPGNVTKSECCCTSvGRAWGSPCE--LCPPPGTDEFRELC 44

TB domain; This domain is also known as the 8 cysteine domain. This family includes the hybrid domains. This cysteine rich repeat is found in TGF binding protein and fibrillin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1622855666 1480 VCSRPLVGkQTTYTECCCLY-GEAWGMQCALCPMKDSDDYAQLC 1522
Cdd:pfam00683    2 RCSNPLPG-NVTKSECCCTSvGRAWGSPCELCPPPGTDEFRELC 44

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 1622855666 1149 DINECEHPGLCGPQGECLNTEGSFHCVCQQGFSisadGRTCE 1190
Cdd:cd00054      1 DIDECASGNPCQNGGTCVNTVGSYRCSCPPGYT----GRNCE 38

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 1622855666 1067 DIDECQHHHLC-AHGQCRNTEGSFQCVCDQGYRasglGDHCE 1107
Cdd:cd00054      1 DIDECASGNPCqNGGTCVNTVGSYRCSCPPGYT----GRNCE 38

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 1622855666 1026 DIDECQQGNLCVN-GQCKNTEGSFRCTCGQGYQL 1058
Cdd:cd00054      1 DIDECASGNPCQNgGTCVNTVGSYRCSCPPGYTG 34

Calcium-binding EGF-like domain;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|..
gi 1622855666   985 DVDECLEPNVCTNG-DCSNLEGSYMCSCHKGYTrtpDHKHCK 1025
Cdd:smart00179    1 DIDECASGNPCQNGgTCVNTVGSYRCECPPGYT---DGRNCE 39

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|..
gi 1622855666   627 DINECQLQGVCPNG-ECLNTMGSYRCTCKIGF 657
Cdd:smart00179    1 DIDECASGNPCQNGgTCVNTVGSYRCECPPGY 32

Calcium-binding EGF domain;

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1622855666 1108 DINECLEDKSVCQR-GDCINTAGSYDCTCPDG 1138
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
                   ....*....|....*....|....*....|..
gi 1622855666  627 DINECQLQGVCPN-GECLNTMGSYRCTCKIGF 657
Cdd:cd00054      1 DIDECASGNPCQNgGTCVNTVGSYRCSCPPGY 32

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 1622855666  1607 DVNECDELNNrmslCKN-AKCINTEGSYKCLCLPGY 1641
Cdd:smart00179    1 DIDECASGNP----CQNgGTCVNTVGSYRCECPPGY 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 1622855666  862 DIDECTQvQHLCS-QGRCENTEGSFLCICPAGFmaseEGTNCI 903
Cdd:cd00054      1 DIDECAS-GNPCQnGGTCVNTVGSYRCSCPPGY----TGRNCE 38

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 1622855666 1607 DVNECDELNNrmslCKN-AKCINTEGSYKCLCLPGY 1641
Cdd:cd00054      1 DIDECASGNP----CQNgGTCVNTVGSYRCSCPPGY 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 1622855666 1108 DINEClEDKSVCQR-GDCINTAGSYDCTCPDGFQLddnKTCQ 1148
Cdd:cd00054      1 DIDEC-ASGNPCQNgGTCVNTVGSYRCSCPPGYTG---RNCE 38

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 1622855666 1173 HCVCQQGFSISADGRTCEDIDE 1194
Cdd:pfam12662    1 TCSCPPGYQLDPDGRTCVDIDE 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
                   ....*....|....*....|....*....|....
gi 1622855666  904 DVDECLRPDVCGEGH-CVNTVGAFRCEyCDSGYR 936
Cdd:cd00054      1 DIDECASGNPCQNGGtCVNTVGSYRCS-CPPGYT 33

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 1622855666  945 DIDECLNPSTC-PDEQCVNSPGSYQCVpCTEGFRG 978
Cdd:cd00054      1 DIDECASGNPCqNGGTCVNTVGSYRCS-CPPGYTG 34

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 1622855666 1009 CSCHKGYTRTPDHKHCKDIDE 1029
Cdd:pfam12662    2 CSCPPGYQLDPDGRTCVDIDE 22

TB domain; This domain is also known as the 8 cysteine domain. This family includes the hybrid domains. This cysteine rich repeat is found in TGF binding protein and fibrillin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1622855666 1304 CDNVLSPNVTKQECCCTS-GAGWGDNCEifPCPVLGTAEFTEMC 1346
Cdd:pfam00683    3 CSNPLPGNVTKSECCCTSvGRAWGSPCE--LCPPPGTDEFRELC 44

TB domain; This domain is also known as the 8 cysteine domain. This family includes the hybrid domains. This cysteine rich repeat is found in TGF binding protein and fibrillin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1622855666 1480 VCSRPLVGkQTTYTECCCLY-GEAWGMQCALCPMKDSDDYAQLC 1522
Cdd:pfam00683    2 RCSNPLPG-NVTKSECCCTSvGRAWGSPCELCPPPGTDEFRELC 44

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 1622855666 1149 DINECEHPGLCGPQGECLNTEGSFHCVCQQGFSisadGRTCE 1190
Cdd:cd00054      1 DIDECASGNPCQNGGTCVNTVGSYRCSCPPGYT----GRNCE 38

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 1622855666 1067 DIDECQHHHLC-AHGQCRNTEGSFQCVCDQGYRasglGDHCE 1107
Cdd:cd00054      1 DIDECASGNPCqNGGTCVNTVGSYRCSCPPGYT----GRNCE 38

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 1622855666 1026 DIDECQQGNLCVN-GQCKNTEGSFRCTCGQGYQL 1058
Cdd:cd00054      1 DIDECASGNPCQNgGTCVNTVGSYRCSCPPGYTG 34

Calcium-binding EGF-like domain;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|..
gi 1622855666   985 DVDECLEPNVCTNG-DCSNLEGSYMCSCHKGYTrtpDHKHCK 1025
Cdd:smart00179    1 DIDECASGNPCQNGgTCVNTVGSYRCECPPGYT---DGRNCE 39

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|..
gi 1622855666   627 DINECQLQGVCPNG-ECLNTMGSYRCTCKIGF 657
Cdd:smart00179    1 DIDECASGNPCQNGgTCVNTVGSYRCECPPGY 32

Calcium-binding EGF domain;

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1622855666 1108 DINECLEDKSVCQR-GDCINTAGSYDCTCPDG 1138
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
                   ....*....|....*....|....*....|..
gi 1622855666  627 DINECQLQGVCPN-GECLNTMGSYRCTCKIGF 657
Cdd:cd00054      1 DIDECASGNPCQNgGTCVNTVGSYRCSCPPGY 32

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....*.
gi 1622855666  1607 DVNECDELNNrmslCKN-AKCINTEGSYKCLCLPGY 1641
Cdd:smart00179    1 DIDECASGNP----CQNgGTCVNTVGSYRCECPPGY 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 1622855666  862 DIDECTQvQHLCS-QGRCENTEGSFLCICPAGFmaseEGTNCI 903
Cdd:cd00054      1 DIDECAS-GNPCQnGGTCVNTVGSYRCSCPPGY----TGRNCE 38

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 1622855666 1607 DVNECDELNNrmslCKN-AKCINTEGSYKCLCLPGY 1641
Cdd:cd00054      1 DIDECASGNP----CQNgGTCVNTVGSYRCSCPPGY 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 1622855666 1108 DINEClEDKSVCQR-GDCINTAGSYDCTCPDGFQLddnKTCQ 1148
Cdd:cd00054      1 DIDEC-ASGNPCQNgGTCVNTVGSYRCSCPPGYTG---RNCE 38

Epidermal growth factor-like domain;

                            10        20
                    ....*....|....*....|....*....
gi 1622855666  1070 ECQHHHLCAHGQCRNTEGSFQCVCDQGYR 1098
Cdd:smart00181    1 ECASGGPCSNGTCINTPGSYTCSCPPGYT 29

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 1622855666 1173 HCVCQQGFSISADGRTCEDIDE 1194
Cdd:pfam12662    1 TCSCPPGYQLDPDGRTCVDIDE 22

Calcium-binding EGF domain;

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1622855666 1607 DVNECDELNNrmsLC-KNAKCINTEGSYKCLCLPG 1640
Cdd:pfam07645    1 DVDECATGTH---NCpANTVCVNTIGSFECRCPDG 32

Calcium-binding EGF domain;

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1622855666  627 DINEC-QLQGVCP-NGECLNTMGSYRCTCKIG 656
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 1622855666 1152 ECEHPGLCGPQGECLNTEGSFHCVCQQGFS 1181
Cdd:cd00053      1 ECAASNPCSNGGTCVNTPGSYRCVCPPGYT 30

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....
gi 1622855666   945 DIDECLNPSTC-PDEQCVNSPGSYQCVpCTEGFR 977
Cdd:smart00179    1 DIDECASGNPCqNGGTCVNTVGSYRCE-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 1622855666 1133 CTCPDGFQLD-DNKTCQDINE 1152
Cdd:pfam12662    2 CSCPPGYQLDpDGRTCVDIDE 22