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* Vitamin K-dependent carboxylation domain *
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Vitamin K-dependent carboxylation [1,2] is the post-translational modification
of glutamic  residues  to form gamma-carboxyglutamate (Gla). Proteins known to
contain Gla are listed below.

 - A number of plasma proteins involved in blood coagulation.   These proteins
   are prothrombin, coagulation factors VII, IX and X, proteins C, S, and Z.
 - Two proteins that  occur  in calcified tissues:  osteocalcin (also known as
   bone-Gla protein, BGP), and matrix Gla-protein (MGP).
 - Cone snail venom peptides: conantokin-G and -T, and conotoxin GS [3].

With the  exception  of  the  snail  toxins,  all  these  proteins  contain an
N-terminal module  of  about  forty  amino acids where the majority of the Glu
residues are carboxylated.  This  domain is  responsible for the high-affinity
binding of calcium ions.  The Gla-domain starts at the N-terminal extremity of
the mature  form of these proteins and ends with a conserved aromatic residue;
a conserved Gla-x(3)-Gla-x-Cys motif [4] is  found in the middle of the domain
which seems to be important for substrate recognition by the carboxylase.

-Consensus pattern: x(12)-E-x(3)-E-x-C-x(6)-[DEN]-x-[LIVMFY]-x(9)-[FYW]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: Trypanosoma   ESAG8   protein   and
 Bacillus subtilis spaB.

-Note: all glutamic residues present in the domain are potential carboxylation
 sites; in coagulation proteins, all are modified to Gla, while in BGP and MGP
 some are not.

-Expert(s) to contact by email: Price P.A.
                                pprice@ucsd.edu

-Last update: December 1992 / Text revised.

[ 1] Friedman P.A., Przysiecki C.T.
     Int. J. Biochem. 19:1-7(1987).
[ 2] Vermeer C.
     Biochem. J. 266:625-636(1990).
[ 3] Haack J.A., Rivier J.E., Parks T.N., Mena E.E., Cruz L.J., Olivera B.M.
     J. Biol. Chem. 265:6025-6029(1990).
[ 4] Price P.A., Fraser J.D., Metz-Virca G.
     Proc. Natl. Acad. Sci. U.S.A. 84:8335-8339(1987).