Gamma-carboxylation of protein precursors Authored: D'Eustachio, P, 2005-03-17 16:24:57 Edited: D'Eustachio, P, 0000-00-00 00:00:00 GENE ONTOLOGYGO:0017187 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). Pubmed10068650 Pubmed10917896 Pubmed11071668 Pubmed11513608 Pubmed8530480 Pubmed8839851 Pubmed9845520 Reactome Database ID Release 43159740 Reactome, http://www.reactome.org ReactomeREACT_1050 PathwayStep3050 PathwayStep3051 PathwayStep3052 PathwayStep3049 PathwayStep3048 PathwayStep3045 PathwayStep3046 PathwayStep3047 pro-factor IX, uncarboxylated + 12 CO2 + 12 O2 + 12 vitamin K hydroquinone -> pro-factor IX + 12 H2O + 12 vitamin K epoxide pro-factor VII, uncarboxylated + 10 CO2 + 10 O2 + 10 vitamin K hydroquinone -> pro-factor VII + 10 H2O + 10 vitamin K epoxide pro-factor X, uncarboxylated + 11 CO2 + 11 O2 + 11 vitamin K hydroquinone -> pro-factor X + 11 H2O + 11 vitamin K epoxide pro-prothrombin, uncarboxylated + 10 CO2 + 10 O2 + 10 vitamin K hydroquinone -> pro-prothrombin + 10 H2O + 10 vitamin K epoxide pro-protein C, uncarboxylated + 8 CO2 + 8 O2 + 8 vitamin K hydroquinone -> pro-protein C + 8 H2O + 8 vitamin K epoxide pro-protein S, uncarboxylated + 11 CO2 + 11 O2 + 11 vitamin K hydroquinone -> pro-protein S + 11 H2O + 11 vitamin K epoxide pro-GAS6, uncarboxylated + 11 CO2 + 11 O2 + 11 vitamin K hydroquinone -> pro-GAS6 + 11 H2O + 11 vitamin K epoxide pro-protein Z, uncarboxylated + 13 CO2 + 13 O2 + 13 vitamin K hydroquinone -> pro-protein Z + 13 H2O + 13 vitamin K epoxide