Calcium-binding EGF domain

In molecular biology, the calcium-binding EGF domain is an EGF-like domain of about forty amino-acid residues found in epidermal growth factor (EGF). This domain is present in a large number of membrane-bound and extracellular, mostly animal, proteins.^{[1][2][3][4][5]} 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.^[6] Calcium-binding may be crucial for numerous protein-protein interactions.

Calcium-binding EGF domain
crystal structure of the human mbl-associated protein 19 (map19)
Identifiers
Symbol	EGF_CA
Pfam	PF07645
Pfam clan	CL0001
InterPro	IPR013091
CDD	cd00054
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

For human coagulation factor IX it has been shown that the calcium-ligands form a pentagonal bipyramid.^[7] The first, third and fourth conserved negatively charged or polar residues are side chain ligands. The latter is possibly hydroxylated.^[6] 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.^[6]