Gla domain
| GLA Domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Anchoring of Coagulation factor VIIa to the membrane through its GLA domain | |||||||||
| Identifiers | |||||||||
| Symbol | Gla | ||||||||
| Pfam | PF00594 | ||||||||
| InterPro | IPR000294 | ||||||||
| PROSITE | PDOC00011 | ||||||||
| SCOP | 1cfi | ||||||||
| SUPERFAMILY | 1cfi | ||||||||
| OPM superfamily | 97 | ||||||||
| OPM protein | 1pfx | ||||||||
| |||||||||
Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla). The Gla residues are responsible for the high-affinity binding of calcium ions. [1][2]
The GLA domain is responsible for the high-affinity binding of calcium ions. It starts at the N-terminal extremity of the mature form of proteins and ends with a conserved aromatic residue; a conserved Gla-x(3)-Gla-x-Cys motif[3] is found in the middle of the domain which seems to be important for substrate recognition by the carboxylase.
The 3D structures of several Gla domains have been solved.[4][5] Calcium ions induce conformational changes in the Gla domain and are necessary for the Gla domain to fold properly. A common structural feature of functional Gla domains is the clustering of N-terminal hydrophobic residues into a hydrophobic patch that mediates interaction with the cell surface membrane.[5]
Subfamilies
- Coagulation factor, Gla region IPR002383
Human proteins containing this domain
BGLAP; F10; F2; F7; F9; GAS6; MGP; PROC; PROS1; PROZ; PRRG1; PRRG2; PRRG3; PRRG4;
References
- ↑ Friedman PA, Przysiecki CT (1987). "Vitamin K-dependent carboxylation". Int. J. Biochem. 19 (1): 1–7. doi:10.1016/0020-711X(87)90116-9. PMID 3106112.
- ↑ Vermeer C (1990). "Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase". Biochem. J. 266 (3): 625–636. PMC 1131186. PMID 2183788.
- ↑ Price PA, Fraser JD, Metz-Virca G (1987). "Molecular cloning of matrix Gla protein: implications for substrate recognition by the vitamin K-dependent gamma-carboxylase". Proc. Natl. Acad. Sci. U.S.A. 84 (23): 8335–8339. doi:10.1073/pnas.84.23.8335. PMC 299537. PMID 3317405.
- ↑ Freedman SJ, Furie BC, Furie B, Baleja JD (1995). "Structure of the metal-free gamma-carboxyglutamic acid-rich membrane binding region of factor IX by two-dimensional NMR spectroscopy". J. Biol. Chem. 270 (14): 7980–7987. doi:10.1074/jbc.270.14.7980. PMID 7713897.
- ↑ 5.0 5.1 Freedman SJ, Furie BC, Furie B, Baleja JD, Blostein MD, Jacobs M (1996). "Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX". J. Biol. Chem. 271 (27): 16227–16236. doi:10.1074/jbc.271.27.16227. PMID 8663165.