EC - Vitamin-K-epoxide reductase (warfarin-sensitive)

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IntEnz Enzyme Nomenclature


Accepted name:
vitamin-K-epoxide reductase (warfarin-sensitive)
Other names:
vitamin K1 epoxide reductase
phylloquinone epoxide reductase
VKORC1 (gene name)
VKORC1L1 (gene name)
Systematic name:
phylloquinone:disulfide oxidoreductase



The enzyme catalyses the reduction of vitamin K 2,3-epoxide, which is formed by the activity of EC, peptidyl-glutamate 4-carboxylase, back to its phylloquinol active form. The enzyme forms a tight complex with EC, protein disulfide-isomerase, which transfers the required electrons from newly-synthesized proteins by catalysing the formation of disulfide bridges. The enzyme acts on the epoxide forms of both phylloquinone (vitamin K1) and menaquinone (vitamin K2). Inhibited strongly by (S)-warfarin and ferulenol.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
CAS Registry Number: 55963-40-1


  1. Lee, J.L. and Fasco, M.J.
    Metabolism of vitamin K and vitamin K 2,3-epoxide via interaction with a common disulfide.
    Biochemistry 23: 2246-2252 (1984). [PMID: 6733086]
  2. Mukharji, I. and Silverman, R.B.
    Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone.
    Proc. Natl. Acad. Sci. USA 82: 2713-2717 (1985). [PMID: 3857611]
  3. Whitlon, D.S., Sadowski, J.A. and Suttie, J.W.
    Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.
    Biochemistry 17: 1371-1377 (1978). [PMID: 646989]
  4. Li, T., Chang, C. Y., Jin, D. Y., Lin, P. J., Khvorova, A., Stafford, D. W.
    Identification of the gene for vitamin K epoxide reductase.
    Nature 427: 541-544 (2004). [PMID: 14765195]
  5. Wajih, N., Hutson, S. M., Wallin, R.
    Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K1 2,3-epoxide reduction.
    J. Biol. Chem. 282: 2626-2635 (2007). [PMID: 17124179]
  6. Spohn, G., Kleinridders, A., Wunderlich, F. T., Watzka, M., Zaucke, F., Blumbach, K., Geisen, C., Seifried, E., Muller, C., Paulsson, M., Bruning, J. C., Oldenburg, J.
    VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding.
    Thromb. Haemost. 101: 1044-1050 (2009). [PMID: 19492146]
  7. Schulman, S., Wang, B., Li, W., Rapoport, T. A.
    Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners.
    Proc. Natl. Acad. Sci. U.S.A. 107: 15027-15032 (2010). [PMID: 20696932]

[EC created 1989 as EC, transferred 2014 to EC, modified 2018]