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- **********************************
- * EF-hand calcium-binding domain *
- **********************************
-
- Many calcium-binding proteins belong to the same evolutionary family and share
- a type of calcium-binding domain known as the EF-hand [1 to 4]. This type of
- domain consists of a twelve residue loop flanked on both side by a twelve
- residue alpha-helical domain. In an EF-hand loop the calcium ion is
- octahedrally coordinated. The six residues involved in the binding are in
- positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X
- and -Z.
-
- We list below the proteins which are known to contain EF-hand regions. For
- each type of protein we have indicated between parenthesis the total number of
- EF-hand regions known or supposed to exist. This number does not include
- regions which clearly have lost their calcium-binding properties, or the
- atypical low-affinity site (which spans thirteen residues) found in the S-100/
- ICaBP family of proteins [5].
-
- - Aequorin and Renilla luciferin binding protein (LBP) (Ca=3).
- - Alpha actinin (Ca=2).
- - Calbindin (Ca=4).
- - Calcineurin B subunit (protein phosphatase 2B regulatory subunit) (Ca=4).
- - Calcium-binding protein from Streptomyces erythraeus (Ca=3?).
- - Calcium-binding protein from Schistosoma mansoni (Ca=2?).
- - Calcium-binding proteins TCBP-23 and TCBP-25 from Tetrahymena thermophila
- (Ca=4?).
- - Calcium-dependent protein kinases (CDPK) from plants (Ca=4).
- - Calcium vector protein from amphoxius (Ca=2).
- - Calcyphosin (thyroid protein p24) (Ca=4?).
- - Calmodulin (Ca=4, except in yeast where Ca=3).
- - Calpain small and large chains (Ca=2).
- - Calretinin (Ca=6).
- - Calcyclin (prolactin receptor associated protein) (Ca=1).
- - Caltractin from Chlamydomonas reinhardtii (Ca=4).
- - Cell Division Control protein 31 (gene CDC31) from yeast (Ca=2?).
- - Diacylglycerol kinase (EC 2.7.1.107) (DGK) (Ca=2).
- - FAD-dependent glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) from
- mammals (Ca=1).
- - Fimbrin (plastin) (Ca=2).
- - Flagellar calcium-binding protein (1f8) from Trypanosoma cruzi (Ca=1 or 2).
- - Intestinal calcium-binding protein (ICaBPs) (Ca=1).
- - MIF related proteins 8 (MRP-8 or CFAG) and 14 (MRP-14) (Ca=1).
- - Myosin regulatory light chains (Ca=1).
- - Oncomodulin (Ca=2).
- - Osteonectin (basement membrane protein BM-40) (SPARC) and proteins that
- contains an 'osteonectin' domain (QR1, matrix glycoprotein SC1) (Ca=1).
- - Parvalbumins alpha and beta (Ca=2).
- - Placental calcium-binding protein (18a2) (nerve growth factor induced
- protein 42a) (p9k) (Ca=1).
- - Recoverins (visinin, hippocalcin, neurocalcin, S-modulin) (Ca=2 to 3).
- - Reticulocalbin (Ca=4).
- - S-100 protein, alpha and beta chains (Ca=1).
- - Sarcoplasmic calcium-binding protein (SCPs) (Ca=2 to 3).
- - Sea urchin proteins Spec 1 (Ca=4), Spec 2 (Ca=4?), Lps-1 (Ca=8).
- - Sorcin V19 from hamster (Ca=2).
- - Spectrin alpha chain (Ca=2).
- - Squidulin (optic lobe calcium-binding protein) from squid (Ca=4).
- - Troponins C; from skeletal muscle (Ca=4), from cardiac muscle (Ca=3), from
- arthropods and molluscs (Ca=2).
-
- There has been a number of attempts [6,7] to develop patterns that pick-up EF-
- hand regions, but these studies were made a few years ago when not so many
- different families of calcium-binding proteins were known. We therefore
- developed a new pattern which takes into account all published sequences. This
- pattern includes the complete EF-hand loop as well as the first residue which
- follows the loop and which seem to always be hydrophobic.
-
- -Consensus pattern:
-
- 1 2 3 4 5 6 7 8 9 10 12
- X Y Z -Y -X -Z
- D-x-[DNS]-{ILVFYW}-[DENSTG]-[DNQGHRK]-{GP}-[LIVMC]-[DENQSTAGC]-x(2)-[DE]-
-
- 13
- [LIVMFYW]
-
- -Sequences known to belong to this class detected by the pattern: ALL, except
- for chicken actinin and human S-100P.
- -Other sequence(s) detected in SWISS-PROT: 52 proteins which are probably not
- calcium-binding and a few proteins for which we have reason to believe that
- they bind calcium: a number of endoglucanases and a xylanase from the
- cellulosome complex of Clostridium [8] and two different isozymes of inositol
- phospholipid-specific phospholipase C [9].
-
- -Note: positions 1 (X), 3 (Y) and 12 (-Z) are the most conserved.
- -Note: the 6th residue in an EF-hand loop is, in most cases a Gly, but the
- number of exceptions to this 'rule' has gradually increased and we felt that
- the pattern should include all the different residues which have been shown
- to exist in this position in functional Ca-binding sites.
- -Note: the pattern will, in some cases, miss one of the EF-hand regions in
- some proteins with multiple EF-hand domains.
-
- -Expert(s) to contact by email: Cox J.A.
- cox@sc2a.unige.ch
- Kretsinger R.H.
- rhk5i@virginia.bitnet
-
- -Last update: June 1994 / Text revised.
-
- [ 1] Kretsinger R.H.
- Cold Spring Harbor Symp. Quant. Biol. 52:499-510(1987).
- [ 2] Moncrief N.D., Kretsinger R.H., Goodman M.
- J. Mol. Evol. 30:522-562(1990).
- [ 3] Nakayama S., Moncrief N.D., Kretsinger R.H.
- J. Mol. Evol. 34:416-448(1992).
- [ 4] Heizmann C.W., Hunziker W.
- Trends Biochem. Sci. 16:98-103(1991).
- [ 5] Kligman D., Hilt D.C.
- Trends Biochem. Sci. 13:437-443(1988).
- [ 6] Gariepy J., Hodges R.S.
- FEBS Lett. 160:1-6(1983).
- [ 7] Haiech J., Sallantin J.
- Biochimie 67:555-560(1985).
- [ 8] Chauvaux S., Beguin P., Aubert J.-P., Bhat K.M., Gow L.A., Wood T.M.,
- Bairoch A.
- Biochem. J. 265:261-265(1990).
- [ 9] Bairoch A., Cox J.A.
- FEBS Lett. 269:454-456(1990).
-