Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle.

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Oldenburg J, Bevans CG, Muller CR, Watzka M

Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle.

Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):347-53.

PubMed ID

16677080 [ View in PubMed

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Abstract

Vitamin K epoxide, a by-product of the carboxylation of blood coagulation factors, is reduced to vitamin K by an enzymatic system possessing vitamin K epoxide reductase (VKOR) activity. This system is the target of coumarin-derived drugs widely used in thrombosis therapy and prophylaxis. Recently, the key protein of the VKOR system has been identified. The human VKORC1 gene maps to chromosome 16 and consists of 3 exons encoding a 163-amino acid integral ER membrane protein with three or four predicted transmembrane alpha- helices. Expression of human VKORC1 in Spodoptera frugiperda (Sf9) cells and in Pichia pastoris results in enhanced VKOR activity over low endogenous constitutive levels. Sequence based search methods reveal that human VKORC1 belongs to a large family of homologous genes found in vertebrates, insects, plants, protists, archea, and bacteria. All orthologs share five completely conserved amino acids, including two cysteines found in a tetrapeptide motif presumably required for redox function. The recent discovery of the VKORC1 gene has initiated renewed interest in understanding VKOR activity. Analysis of VKORC1 protein structure and function will be crucial in understanding the VKOR catalytic mechanism, how anticoagulant drugs modulate VKOR activity, and the role of VKORC1 in downstream physiological and pathological pathways.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Menadione	Vitamin K epoxide reductase complex subunit 1	Protein	Humans	Yes	Cofactor	Details
Menadione	Vitamin K epoxide reductase complex subunit 1-like protein 1	Protein	Humans	Yes	Cofactor	Details