RGD Reference Report - Vitamin K 2,3-epoxide reductase and the vitamin K-dependent gamma-carboxylation system. - Rat Genome Database

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Vitamin K 2,3-epoxide reductase and the vitamin K-dependent gamma-carboxylation system.

Authors: Wallin, R  Sane, DC  Hutson, SM 
Citation: Wallin R, etal., Thromb Res. 2002 Nov 25;108(4):221-6.
RGD ID: 1598952
Pubmed: PMID:12617985   (View Abstract at PubMed)

Vitamin K is an essential cofactor for post translational gamma-carboxylation of vitamin K-dependent coagulation factors. The modification is carried out by a system of integral proteins of the endoplasmic reticulum (ER) membrane where the warfarin sensitive vitamin K 2,3-epoxide reductase (VKOR) produces the reduced hydroquinone form of vitamin K (vit.KH(2)) needed by the gamma-carboxylase as the active cofactor. Currently, we have only limited knowledge about how the system functions at the molecular level. VKOR harbors a thiol red/ox center that is essential for electron transfer leading to vitamin K reduction. Reduction of this center with hydrophilic and hydrophobic trialkylphosphines shows that it is located in a hydrophobic environment which must be accessible by an as yet unidentified in vivo reductant of the center. Furthermore, we have addressed the question of whether VKOR or the gamma-carboxylase is the rate-limiting step in the vitamin K-dependent gamma-caboxylation system. A detailed kinetic analysis of an in vitro preparation of the system was undertaken in which gamma-carboxylation of the carboxylase peptide substrate FLEEL was measured as the gamma-carboxylation capacity of the system. Adding VKOR to the test system increased the gamma-carboxylation capacity of the system suggesting that VKOR is the rate-limiting step in the system. This finding puts VKOR in a central position to regulate biosynthesis of biologically active vitamin K-dependent proteins.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GgcxRatpeptidyl-glutamic acid carboxylation  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GgcxRatpeptide binding  ICGO:0017187 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ggcx  (gamma-glutamyl carboxylase)


Additional Information