Reactome | Gamma-carboxylation of protein precursors

Gamma-carboxylation of protein precursors

Stable Identifier

R-HSA-159740

Type

Pathway

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane

ReviewStatus

5/5

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Gamma-carboxylation of protein precursors

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Gamma-carboxylation of a cluster of glutamate residues near the amino termini of thrombin, factor VII, factor IX, factor X, protein C, protein S, protein Z, and Gas 6 is required for these proteins to bind Ca++ and function efficiently in blood clotting. A single enzyme, vitamin K-dependent gamma-carboxylase, catalyzes the gamma-carboxylation of all eight proteins involved in clotting (Morris et al. 1995; Brenner et al. 1998; Spronk et al. 2000). In the carboxylation reaction, the enzyme binds its substrate protein via a sequence motif on the amino terminal side of the glutamate residues to be carboxylated (Furie et al. 1999), then processively carboxylates all glutamates in the cluster before releasing the substrate (Morris et al. 1995; Berkner 2000; Stenina et al. 2001). The reaction occurs in the endoplasmic reticulum (Bristol et al. 1996).

Literature References

PubMed ID	Title	Journal	Year
10068650	Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid Furie, B, Bouchard, BA, Furie, BC	Blood	1999
10917896	The vitamin K-dependent carboxylase Berkner, KL	J Nutr	2000
9845520	A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors Brenner, B, Sanchez-Vega, B, Wu, SM, Lanir, N, Stafford, DW, Solera, J	Blood	1998
11071668	Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors Spronk, HM, Farah, RA, Buchanan, GR, Vermeer, C, Soute, BA	Blood	2000
11513608	Tethered processivity of the vitamin K-dependent carboxylase: factor IX is efficiently modified in a mechanism which distinguishes Gla's from Glu's and which accounts for comprehensive carboxylation in vivo Stenina, O, Pudota, BN, McNally, BA, Hommema, EL, Berkner, KL	Biochemistry	2001