delta serrate ligand;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 110735443   159 WSQDLHSSGRTDLKYSYRFVCDEHYYGEGCSVFCRPRDDAFGHFTCGERGEKVCNPGWKGPYC 221
Cdd:smart00051   1 WSTDLHIGGRTFLEYQIRVTCDENYYGEGCNKFCRPRDDFFGHYTCDENGNKGCLEGWMGPYC 63

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 110735443 443 NVDDCAS-SPCANGGTCRDGVNDFSCTCPPGYTGRNC 478
Cdd:cd00054    1 DIDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

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 110735443 406 IDYCSS-SPCSNGAKCVDLGDAYLCRCQAGFSGRHC 440
Cdd:cd00054    2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

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
                 ....*....|....*....|....*....
gi 110735443 489 PCHNGATCHERGHRYVCECARGYGGPNCQ 517
Cdd:cd00054   10 PCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

delta serrate ligand;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 110735443   159 WSQDLHSSGRTDLKYSYRFVCDEHYYGEGCSVFCRPRDDAFGHFTCGERGEKVCNPGWKGPYC 221
Cdd:smart00051   1 WSTDLHIGGRTFLEYQIRVTCDENYYGEGCNKFCRPRDDFFGHYTCDENGNKGCLEGWMGPYC 63

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 110735443 329 IDECD-PSPCKNGGSCTDLENSYSCTCPPGFYGKICE 364
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 110735443 288 DLNYCTHHKPCKNGATCTNTgQGSYTCSCRPGYTGATCE 326
Cdd:cd00054    1 DIDECASGNPCQNGGTCVNT-VGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 110735443   443 NVDDCAS-SPCANGGTCRDGVNDFSCTCPPGYT-GRNC 478
Cdd:smart00179   1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNC 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 110735443 406 IDYCSS-SPCSNGAKCVDLGDAYLCRCQAGFSGRHC 440
Cdd:cd00054    2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

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 110735443  332 CDPSPCKNGGSCTDLENSYSCTCPPGFYGK 361
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGK 30

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 110735443  409 CSSSPCSNGAKCVDLGDAYLCRCQAGFSGRH 439
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGKR 31

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 110735443  370 CADGPCFNGGRCSDSPdGGYSCRCPVGYSG 399
Cdd:pfam00008   1 CAPNPCSNGGTCVDTP-GGYTCICPEGYTG 29

delta serrate ligand;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 110735443   159 WSQDLHSSGRTDLKYSYRFVCDEHYYGEGCSVFCRPRDDAFGHFTCGERGEKVCNPGWKGPYC 221
Cdd:smart00051   1 WSTDLHIGGRTFLEYQIRVTCDENYYGEGCNKFCRPRDDFFGHYTCDENGNKGCLEGWMGPYC 63

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 110735443 329 IDECD-PSPCKNGGSCTDLENSYSCTCPPGFYGKICE 364
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 110735443 288 DLNYCTHHKPCKNGATCTNTgQGSYTCSCRPGYTGATCE 326
Cdd:cd00054    1 DIDECASGNPCQNGGTCVNT-VGSYRCSCPPGYTGRNCE 38

Calcium-binding EGF-like domain;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 110735443   443 NVDDCAS-SPCANGGTCRDGVNDFSCTCPPGYT-GRNC 478
Cdd:smart00179   1 DIDECASgNPCQNGGTCVNTVGSYRCECPPGYTdGRNC 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 110735443 406 IDYCSS-SPCSNGAKCVDLGDAYLCRCQAGFSGRHC 440
Cdd:cd00054    2 IDECASgNPCQNGGTCVNTVGSYRCSCPPGYTGRNC 37

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 110735443  332 CDPSPCKNGGSCTDLENSYSCTCPPGFYGK 361
Cdd:pfam00008   1 CAPNPCSNGGTCVDTPGGYTCICPEGYTGK 30

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 110735443  409 CSSSPCSNGAKCVDLGDAYLCRCQAGFSGRH 439
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 110735443 292 CTHHKPCKNGATCTNTGqGSYTCSCRPGYTGA-TCE 326
Cdd:cd00053    2 CAASNPCSNGGTCVNTP-GSYRCVCPPGYTGDrSCE 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 110735443  370 CADGPCFNGGRCSDSPdGGYSCRCPVGYSG 399
Cdd:pfam00008   1 CAPNPCSNGGTCVDTP-GGYTCICPEGYTG 29

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
                 ....*....|....*....|....*....
gi 110735443 489 PCHNGATCHERGHRYVCECARGYGGPNCQ 517
Cdd:cd00054   10 PCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

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 110735443  337 CKNGGSCTDLENSYSCTCPPGF 358
Cdd:pfam12661   1 CQNGGTCVDGVNGYKCQCPPGY 22