A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown [ PUBMED:2288911 PUBMED:6334307 PUBMED:3534958 expand

A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown [ PUBMED:2288911 PUBMED:6334307 PUBMED:3534958 PUBMED:6607417 PUBMED:3282918 ] to be present in a large number of membrane-bound and extracellular, mostly animal, proteins. Many of these proteins require calcium for their biological function, and a calcium-binding site has been found at the N-terminal of some EGF-like domains [ PUBMED:1527084 ]. Calcium-binding may be crucial for numerous protein-protein interactions.

A common feature of all EGF-like domains is that they are found in the extracellular domain of membrane-bound proteins or in proteins known to besecreted (exception: prostaglandin G/H synthase). The EGF-like domain includes six cysteine residues which have been shown to be involved in disulfide bonds. The structure of several EGF-like domains has been solved. The fold consists of two-stranded β-sheet followed by a loop to a C-terminal shorttwo-stranded sheet.

As in non-calcium binding EGF-like domains, there are six conserved cysteines and the structure of both types is very similar as calcium-binding induces only strictly local structural changes [ PUBMED:1527084 ].

 +------------------+ +---------+ | | | | nxnnC-x(3,14)-C-x(3,7)-CxxbxxxxaxC-x(1,6)-C-x(8,13)-Cx | |  +------------------+'n': negatively charged or polar residue [DEQN]'b': possibly beta-hydroxylated residue [DN]'a': aromatic amino acid'C': cysteine, involved in disulphide bond'x': any amino acid.