N terminus of Notch ligand C2-like domain; This entry represents a region of conserved sequence at the N terminus of several Notch ligand proteins. The entry has been extended to correspond to the C2-like domain defined by the protein structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157820681   27 SGIFQLRLQEFANERGMLANGRPCEPG-----------CRTFFRICLKHYQATFS-EGPCTFGNVSTPVLGTNSFVIRDK 94
Cdd:pfam07657   1 SGYFELQLLSFENPNGRLANGNCCDGGrsssdgqcrdeCDTYFRVCLKEYQANVSpDGPCTFGSGSTPVLGGNSFTLPGL 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 157820681   95 NSGSGRNPLQLPFNFTWPGTFSLNIQAWHTPGDDLRPETspGNSLISQIIIQGSLAVGKNWKSDEQNNTLTRLRYSYRV 173
Cdd:pfam07657  81 LKGSFRGPIVIPFQFAWPGSFTLIVEAWDEDNSTDSGSD--NPRLIERAIHQGMLNPGDEWQTLRHNGGVAELEYSYRV 157

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 157820681 328 CAS-NPCRNGGSCKDHENSYHCLCPPGYYGQHCE 360
Cdd:cd00054    5 CASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 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 157820681 441 ISDCA-RSPCAHGGTCHDLENGPVCTCPAGFSGRRCE 476
Cdd:cd00054    2 IDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 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 157820681 369 SPCFNGGSCRerNQGASYACECPPNFTGSNCE 400
Cdd:cd00054    9 NPCQNGGTCV--NTVGSYRCSCPPGYTGRNCE 38

N terminus of Notch ligand C2-like domain; This entry represents a region of conserved sequence at the N terminus of several Notch ligand proteins. The entry has been extended to correspond to the C2-like domain defined by the protein structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157820681   27 SGIFQLRLQEFANERGMLANGRPCEPG-----------CRTFFRICLKHYQATFS-EGPCTFGNVSTPVLGTNSFVIRDK 94
Cdd:pfam07657   1 SGYFELQLLSFENPNGRLANGNCCDGGrsssdgqcrdeCDTYFRVCLKEYQANVSpDGPCTFGSGSTPVLGGNSFTLPGL 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 157820681   95 NSGSGRNPLQLPFNFTWPGTFSLNIQAWHTPGDDLRPETspGNSLISQIIIQGSLAVGKNWKSDEQNNTLTRLRYSYRV 173
Cdd:pfam07657  81 LKGSFRGPIVIPFQFAWPGSFTLIVEAWDEDNSTDSGSD--NPRLIERAIHQGMLNPGDEWQTLRHNGGVAELEYSYRV 157

Delta serrate ligand; This family has been redefined to correspond to the EGF-like domain defined by structure.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 157820681  175 CSDNYYGDSCSRLCKKRDDHFGHYECQPDGSLSCLPGWTGKYCDQP 220
Cdd:pfam01414   1 CDENYYGSTCSKFCRPRDDKFGHYTCDANGNKVCLPGWTGPYCDKP 46

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 157820681 284 DLNYCTHHSPCKNGSTCSNsGPRGYTCTCLPGYTGEHCE 322
Cdd:cd00054    1 DIDECASGNPCQNGGTCVN-TVGSYRCSCPPGYTGRNCE 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 157820681 441 ISDCA-RSPCAHGGTCHDLENGPVCTCPAGFSGRRCE 476
Cdd:cd00054    2 IDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 157820681  328 CASNPCRNGGSCKDHENSYHCLCPPGYYGQH 358
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|.
gi 157820681   447 SPCAHGGTCHDLENGPVCTCPAGFS-GRRCE 476
Cdd:smart00179   9 NPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 157820681   403 VDRCTS-NPCANGGQCLNRGPSRTCRCRPGFT-GTHCE 438
Cdd:smart00179   2 IDECASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 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 157820681 369 SPCFNGGSCRerNQGASYACECPPNFTGSNCE 400
Cdd:cd00054    9 NPCQNGGTCV--NTVGSYRCSCPPGYTGRNCE 38

N terminus of Notch ligand C2-like domain; This entry represents a region of conserved sequence at the N terminus of several Notch ligand proteins. The entry has been extended to correspond to the C2-like domain defined by the protein structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157820681   27 SGIFQLRLQEFANERGMLANGRPCEPG-----------CRTFFRICLKHYQATFS-EGPCTFGNVSTPVLGTNSFVIRDK 94
Cdd:pfam07657   1 SGYFELQLLSFENPNGRLANGNCCDGGrsssdgqcrdeCDTYFRVCLKEYQANVSpDGPCTFGSGSTPVLGGNSFTLPGL 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 157820681   95 NSGSGRNPLQLPFNFTWPGTFSLNIQAWHTPGDDLRPETspGNSLISQIIIQGSLAVGKNWKSDEQNNTLTRLRYSYRV 173
Cdd:pfam07657  81 LKGSFRGPIVIPFQFAWPGSFTLIVEAWDEDNSTDSGSD--NPRLIERAIHQGMLNPGDEWQTLRHNGGVAELEYSYRV 157

Delta serrate ligand; This family has been redefined to correspond to the EGF-like domain defined by structure.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 157820681  175 CSDNYYGDSCSRLCKKRDDHFGHYECQPDGSLSCLPGWTGKYCDQP 220
Cdd:pfam01414   1 CDENYYGSTCSKFCRPRDDKFGHYTCDANGNKVCLPGWTGPYCDKP 46

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 157820681 284 DLNYCTHHSPCKNGSTCSNsGPRGYTCTCLPGYTGEHCE 322
Cdd:cd00054    1 DIDECASGNPCQNGGTCVN-TVGSYRCSCPPGYTGRNCE 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 157820681 441 ISDCA-RSPCAHGGTCHDLENGPVCTCPAGFSGRRCE 476
Cdd:cd00054    2 IDECAsGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 157820681  328 CASNPCRNGGSCKDHENSYHCLCPPGYYGQH 358
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31

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 157820681 329 ASNPCRNGGSCKDHENSYHCLCPPGYYGQ-HCE 360
Cdd:cd00053    4 ASNPCSNGGTCVNTPGSYRCVCPPGYTGDrSCE 36

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 157820681  444 CARSPCAHGGTCHDLENGPVCTCPAGFSGRR 474
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31

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 157820681 407 TSNPCANGGQCLNRGPSRTCRCRPGFTG-THCE 438
Cdd:cd00053    4 ASNPCSNGGTCVNTPGSYRCVCPPGYTGdRSCE 36

Human growth factor-like EGF; hEGF, or human growth factor-like EGF, domains have six conserved residues disulfide-bonded into the characteriztic 'ababcc' pattern. They are involved in growth and proliferation of cells, in proteins of the Notch/Delta pathway, neurogulin and selectins. hEGFs are also found in mosaic proteins with four-disulfide laminin EGFs such as aggrecan and perlecan. 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 Cys residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs. In hEGFs the C-terminal thiol resides in the beta-turn, resulting in shorter loop-lengths between the Cys residues of disulfide 'c', typically C[8-9]XC. These shorter loop-lengths are also typical of the four-disulfide EGF domains, laminin ad integrin. Tandem hEGF domains have six linking residues between terminal cysteines of adjacent domains. hEGF domains may or may not bind calcium in the linker region. hEGF domains with the consensus motif CXD4X[F,Y]XCXC are hydroxylated exclusively in the Asp residue.

                          10        20
                  ....*....|....*....|..
gi 157820681  333 CRNGGSCKDHENSYHCLCPPGY 354
Cdd:pfam12661   1 CQNGGTCVDGVNGYKCQCPPGY 22

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 157820681 445 ARSPCAHGGTCHDLENGPVCTCPAGFSG-RRCE 476
Cdd:cd00053    4 ASNPCSNGGTCVNTPGSYRCVCPPGYTGdRSCE 36