Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1)

VKCFD2; VKOR; Vitamin K Dependent Clotting Factors Deficiency 2; Vitamin K1 2,3-epoxide reductase subunit 1

SPN	P847
HGNC	23663
MGI	106442
PubMed	14765194
RGD	1303107
UniProt	Q9BQB6
Wiki	VKORC1

Vitamin K is essential for blood clotting but must be enzymatically activated. This enzymatically activated form of vitamin K is a reduced form required for the carboxylation of glutamic acid residues in some blood-clotting proteins.

VKORC1 is responsible for reducing vitamin K 2,3-epoxide to the enzymatically activated form. Fatal bleeding can be caused by vitamin K deficiency and by the vitamin K antagonist warfarin, and it is the product of this gene that is sensitive to warfarin. In humans, mutations in this gene can be associated with deficiencies in vitamin-K-dependent clotting factors and, in humans and rats, with warfarin resistance. Two pseudogenes have been identified on chromosome 1 and the X chromosome. Two alternatively spliced transcripts encoding different isoforms have been described.

Reference

"Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2."
Nature 427:537-541(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of the gene for vitamin K epoxide reductase."
Nature 427:541-544(2004) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

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Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]

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Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]

"Vitamin K epoxide reductase: homology, active site and catalytic mechanism."
Trends Biochem. Sci. 29:289-292(2004) [PubMed] [Europe PMC] [Abstract]

"The genetic basis of resistance to anticoagulants in rodents."
Genetics 170:1839-1847(2005) [PubMed] [Europe PMC] [Abstract]

"Membrane topology mapping of vitamin K epoxide reductase by in vitro translation/cotranslocation."
J. Biol. Chem. 280:16410-16416(2005) [PubMed] [Europe PMC] [Abstract]

"Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin."
Thromb. Haemost. 94:780-786(2005) [PubMed] [Europe PMC] [Abstract]

"Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners."
Proc. Natl. Acad. Sci. U.S.A. 107:15027-15032(2010) [PubMed] [Europe PMC] [Abstract]

"Novel insight into the mechanism of the vitamin K oxidoreductase (VKOR): electron relay through Cys43 and Cys51 reduces VKOR to allow vitamin K reduction and facilitation of vitamin K-dependent protein carboxylation."
J. Biol. Chem. 286:7267-7278(2011) [PubMed] [Europe PMC] [Abstract]

"Human vitamin K epoxide reductase and its bacterial homologue have different membrane topologies and reaction mechanisms."
J. Biol. Chem. 287:33945-33955(2012) [PubMed] [Europe PMC] [Abstract]

"Membrane topology for human vitamin K epoxide reductase."
J. Thromb. Haemost. 12:112-114(2014) [PubMed] [Europe PMC] [Abstract]

"Thirteen novel VKORC1 mutations associated with oral anticoagulant resistance: insights into improved patient diagnosis and treatment."
J. Thromb. Haemost. 9:109-118(2011) [PubMed] [Europe PMC] [Abstract]