S
IPR018097

EGF-like calcium-binding, conserved site

InterPro entry
Short nameEGF_Ca-bd_CS

Description

A sequence of about forty amino-acid residues found in epidermal growth factor (EGF) has been shown
[1, 2, 3, 4, 5]
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
[6]
. Calcium-binding may be crucial for numerous protein-protein interactions.

For human coagulation factor IX it has been shown
[7]
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)
[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]
.

                             +------------------+        +---------+
                             |                  |        |         |
               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.

References

1.The many faces of epidermal growth factor repeats. Davis CG. New Biol. 2, 410-9, (1990). PMID: 2288911

2.Vaccinia virus 19-kilodalton protein: relationship to several mammalian proteins, including two growth factors. Blomquist MC, Hunt LT, Barker WC. Proc. Natl. Acad. Sci. U.S.A. 81, 7363-7, (1984). View articlePMID: 6334307

3.[Similar domains in different proteins: detection and significance] Barker WC, Johnson GC, Hunt LT, George DG, Tsugita A. Tanpakushitsu Kakusan Koso 54-68, (1986). PMID: 3534958

4.Computer-based characterization of epidermal growth factor precursor. Doolittle RF, Feng DF, Johnson MS. Nature 307, 558-60, (1984). View articlePMID: 6607417

5.Structure and function of epidermal growth factor-like regions in proteins. Appella E, Weber IT, Blasi F. FEBS Lett. 231, 1-4, (1988). View articlePMID: 3282918

6.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. Selander-Sunnerhagen M, Ullner M, Persson E, Teleman O, Stenflo J, Drakenberg T. J. Biol. Chem. 267, 19642-9, (1992). View articlePMID: 1527084

7.The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions. Rao Z, Handford P, Mayhew M, Knott V, Brownlee GG, Stuart D. Cell 82, 131-41, (1995). View articlePMID: 7606779

GO terms

biological process

  • None

cellular component

  • None

Cross References

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