A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown 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 terminus of some EGF-like domains . Calcium-binding may be crucial for numerous protein-protein interactions.For human coagulation factor IX it has been shown that the calcium-ligands form a pentagonal bipyramid. The first third and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated (see aspartic acid and asparagine hydroxylation site) . A conserved aromatic residue as well as the second conserved negative residue are thought to be involved in stabilising the calcium-binding site.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 .
+------------------+ +---------+ | | | | 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.