VKORC1
Domain
Partially oxidized VKORC1 forms a cysteine adduct with substrates, vitamin K 2,3-epoxide, inducing a closed conformation, juxtaposing all cysteines (S-S or SH) for unimpeded electron transfer (PubMed:33154105). VKOR becomes fully oxidized with an open conformation that releases reaction products, vitamin K quinone, or hydroquinone (PubMed:33154105). Cys-132 and Cys-135 constitute the catalytic redox-active center (PubMed:33154105). Cys-43 and Cys-51 are the cysteine pair that mediates transfer of reducing equivalents during catalysis (PubMed:33154105).
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.
Involvement in disease
Combined deficiency of vitamin K-dependent clotting factors 2
VKCFD2
VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K.
None
The disease is caused by variants affecting the gene represented in this entry.
Coumarin resistance
CMRES
A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the VKOR family.
Tissue Specificity
Expressed at highest levels in fetal and adult liver, followed by fetal heart, kidney, and lung, adult heart, and pancreas.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
VKOR, MSTP134, MSTP576, UNQ308/PRO351, VKORC1, Vitamin K epoxide reductase complex subunit 1