Calcium-binding EGF domain explained

Symbol:	EGF_CA
Calcium-binding EGF domain
Pfam:	PF07645
Pfam Clan:	CL0001
Interpro:	IPR013091
Cdd:	cd00054

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.

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]

Notes and References

1. Davis CG . The many faces of epidermal growth factor repeats . New Biol. . 2 . 5 . 410–9 . May 1990 . 2288911 .
2. Blomquist MC, Hunt LT, Barker WC . Vaccinia virus 19-kilodalton protein: relationship to several mammalian proteins, including two growth factors . Proc. Natl. Acad. Sci. U.S.A. . 81 . 23 . 7363–7 . December 1984 . 6334307 . 392146 . 10.1073/pnas.81.23.7363. 1984PNAS...81.7363B . free .
3. Barker WC, Johnson GC, Hunt LT, George DG, Tsugita A . [Similar domains in different proteins: detection and significance] . ja . Tanpakushitsu Kakusan Koso . 29 Suppl . 54–68 . June 1986 . 3534958 .
4. Doolittle RF, Feng DF, Johnson MS . Computer-based characterization of epidermal growth factor precursor . Nature . 307 . 5951 . 558–60 . 1984 . 6607417 . 10.1038/307558a0. 1984Natur.307..558D . 4305008 .
5. Appella E, Weber IT, Blasi F . Structure and function of epidermal growth factor-like regions in proteins . FEBS Lett. . 231 . 1 . 1–4 . April 1988 . 3282918 . 10.1016/0014-5793(88)80690-2. 36825870 . free .
6. Selander-Sunnerhagen M, Ullner M, Persson E, Teleman O, Stenflo J, Drakenberg T . How an epidermal growth factor (EGF)-like domain binds calcium. High resolution NMR structure of the calcium form of the NH2-terminal EGF-like domain in coagulation factor X . J. Biol. Chem. . 267 . 27 . 19642–9 . September 1992 . 10.2210/pdb1ccf/pdb . 1527084 .
7. Rao Z, Handford P, Mayhew M, Knott V, Brownlee GG, Stuart D . The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions . Cell . 82 . 1 . 131–41 . July 1995 . 7606779 . 10.1016/0092-8674(95)90059-4. 8741348 . free .