Vitamin K epoxide reductase complex subunit 1

Function

Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.

Classification

Family (Pfam)

PF07884 VKOR

InterPro

VKOR, VKOR_sf, VKORC1/VKORC1L1

Functional cluster

Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 6

• 6WV3 X-ray 2.20A
• 6WV4 X-ray 3.01A
• 6WV5 X-ray 2.80A
• 6WV6 X-ray 2.70A
• 6WV7 X-ray 2.48A
• 6WVH X-ray 1.99A

A predicted model is available from AlphaFold.

Gene Ontology · 11

• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005789 endoplasmic reticulum membrane
• GO:0048038 quinone binding
• GO:0047058 vitamin-K-epoxide reductase (warfarin-insensitive) activity
• GO:0047057 vitamin-K-epoxide reductase (warfarin-sensitive) activity
• GO:0007596 blood coagulation
• GO:0060348 bone development
• GO:0017187 peptidyl-glutamic acid carboxylation
• GO:0042373 vitamin K metabolic process
• GO:0006805 xenobiotic metabolic process

Disease associations

• coumarin resistance MONDO:0007390
• vitamin K-dependent clotting factors, combined deficiency of, type 2 MONDO:0011837

Drugs targeting this protein · 7

• WARFARIN POTASSIUM inhibitor
• WARFARIN SODIUM inhibitor
• PHENPROCOUMON inhibitor
• DICUMAROL inhibitor
• TECARFARIN inhibitor
• ACENOCOUMAROL inhibitor
• PHENINDIONE inhibitor

Related proteins · sequence + function similarity

• Vitamin K epoxide reductase complex subunit 1 0.98
• Vitamin K epoxide reductase complex subunit 1 0.98
• Vitamin K epoxide reductase complex subunit 1 0.97
• Vitamin K epoxide reductase complex subunit 1-like protein 1 0.92
• Vitamin K epoxide reductase complex subunit 1-like protein 1 0.92
• Vitamin K epoxide reductase complex subunit 1-like protein 1 0.92
• Vitamin K epoxide reductase complex subunit 1-like protein 1 0.90
• Disulfide bond formation protein B 2 0.60
• Disulfide bond formation protein B 2 0.59
• Disulfide bond formation protein B 0.58
• Disulfide bond formation protein B 0.58
• Disulfide bond formation protein B 2 0.58

Co-cited proteins · studied together in the literature

• Vitamin K epoxide reductase complex subunit 1 3 shared papers
• Vitamin K epoxide reductase complex subunit 1-like protein 1 2 shared papers
• Vitamin K epoxide reductase complex subunit 1 1 shared papers
• Vitamin K epoxide reductase complex subunit 1-like protein 1 1 shared papers
• Vitamin K epoxide reductase complex subunit 1-like protein 1 1 shared papers
• Vitamin K epoxide reductase complex subunit 1-like protein 1 1 shared papers

Literature · 16 cited papers

• Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation. Science · 2021
• Membrane topology for human vitamin K epoxide reductase. J. Thromb. Haemost. · 2014
• Human vitamin K epoxide reductase and its bacterial homologue have different membrane topologies and reaction mechanisms. J. Biol. Chem. · 2012
• 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. · 2011
• Thirteen novel VKORC1 mutations associated with oral anticoagulant resistance: insights into improved patient diagnosis and treatment. J. Thromb. Haemost. · 2011
• Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners. Proc. Natl. Acad. Sci. U.S.A. · 2010
• 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. · 2005
• The genetic basis of resistance to anticoagulants in rodents. Genetics · 2005
• Membrane topology mapping of vitamin K epoxide reductase by in vitro translation/cotranslocation. J. Biol. Chem. · 2005
• The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Vitamin K epoxide reductase: homology, active site and catalytic mechanism. Trends Biochem. Sci. · 2004
• … and 4 more in the literature graph