LMPD Database

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LMP003452

UniProt Annotations

Entry Information
Gene Namevitamin K epoxide reductase complex, subunit 1
Protein EntryVKOR1_HUMAN
UniProt IDQ9BQB6
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=MST576; IsoId=Q9BQB6-1; Sequence=Displayed; Name=2; Synonyms=MST134; IsoId=Q9BQB6-2; Sequence=VSP_013363; Name=3; IsoId=Q9BQB6-3; Sequence=VSP_043407; Note=No experimental confirmation available.;
Catalytic Activity2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol = 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl- 1,4-naphthoquinone + 1,4-dithiothreitol. {ECO
DiseaseCombined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2) [MIM
DiseaseCoumarin resistance (CMRES) [MIM
DomainThe number of transmembrane domains and the membrane topology are controversial; supporting evidence is available both for models with three transmembrane domains (PubMed:15716279 and PubMed:22923610) and four transmembrane domains (PubMed:20696932 and PubMed:20978134). According to PubMed:15716279 and PubMed:22923610 the N-terminus of the protein is in the endoplasmic reticulum lumen, while the C-terminus is in the cytosol, which is in favor of three transmembrane domains. According to PubMed:20696932, both N-terminus and C-terminus are in the cytosol, indicating the presence of four transmembrane domains. Besides, the 3D-structure of a bacterial ortholog shows four transmembrane domains. Moreover, proteins that reside in the endoplasmic reticulum lumen can catalyze the reduction of the active site cysteines, possibly via Cys-43 and Cys-51 (PubMed:20696932 and PubMed:20978134), but less efficiently than the synthetic compound dithiothreitol (in vitro). Location of Cys- 43 and Cys-51 in the endoplasmic reticulum lumen would be in agreement with four transmembrane domains. Again, these data are controversial, and papers do not agree on the effects of mutating Cys-43 and Cys-51, probably because of differences in the assay systems.
Enzyme RegulationInhibited by warfarin (coumadin). {ECO
FunctionInvolved 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. {ECO
MiscellaneousThe location of two cysteine active-site residues within a proposed transmembrane is consistent both with the known hydrophobic environment of the thiol redox site of the enzyme and with the lipophilicity of vitamin K and warfarin (coumadin).
Sequence CautionSequence=AAQ88821.1; Type=Erroneous initiation; Evidence= ;
SimilarityBelongs to the VKOR family.
Subcellular LocationEndoplasmic reticulum membrane {ECO
Tissue SpecificityExpressed at highest levels in fetal and adult liver, followed by fetal heart, kidney, and lung, adult heart, and pancreas.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/vkorc1/";