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Literature summary for 1.17.4.4 extracted from

  • Wu, S.; Liu, S.; Davis, C.H.; Stafford, D.W.; Kulman, J.D.; Pedersen, L.G.
    A hetero-dimer model for concerted action of vitamin K carboxylase and vitamin K reductase in vitamin K cycle (2011), J. Theor. Biol., 279, 143-149.
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
D36V naturally occuring mutation, warfarin resistant mutant Homo sapiens
L128R naturally occuring mutation, warfarin resistant mutant Homo sapiens
R58G, naturally occuring mutation, warfarin resistant mutant Homo sapiens
V29L naturally occuring mutation, warfarin resistant mutant Homo sapiens
V45A naturally occuring mutation, warfarin resistant mutant Homo sapiens
V66M naturally occuring mutation, warfarin resistant mutant Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
warfarin non-competitive inhibitor, displacement of the warfarin binding site away from the vitamin K binding site by at least one turn of the transmembrane helix. The fully extended phenyl group of S-warfarin may interact with the phenyl fragment of Tyr139 of VKOR in a stacking configuration. Binding of S-warfarin to VKOR in the presence of vitamin K could modify, i.e. reduce the rate of flip-flop of lipid membrane, ultimately leading to the decrease of the amount of the vitamin K hydroquinone form Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
endoplasmic reticulum membrane
-
Homo sapiens 5789
-
membrane transmembrane protein with 5 transmembrane helices, membrane topology, overview Homo sapiens 16020
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O Homo sapiens
-
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
-
Homo sapiens 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
?

Synonyms

Synonyms Comment Organism
vitamin K epoxide reductase
-
Homo sapiens
VKOR
-
Homo sapiens
VKORC1
-
Homo sapiens

General Information

General Information Comment Organism
metabolism vitamin K carboxylase converts vitamin K, in the vitamin K cycle, to an alkoxide-epoxide form which then reacts with CO2 and glutamate to generate gamma-carboxyglutamic acid. Subsequently, vitamin K epoxide reductase converts the alkoxide-epoxide to a hydroquinone form. By recycling vitamin K, the two integral-membrane proteins maintain vitamin K levels and sustain the blood coagulation cascade. Heterodimeric form of vitamin K carboxylase and vitamin K epoxide reductase may explain the efficient oxidation and reduction of vitamin K during the vitamin K cycle Homo sapiens
additional information possible heterodimeric form of vitamin K carboxylase and vitamin K epoxide reductase during the vitamin K cycle and co-localization on the lumenal side of endoplasmic reticulum membrane, molecular dynamics simulations and modeling, overview Homo sapiens
physiological function the enzyme is involved in the vitamin K cycle maintaining vitamin K levels and sustain the blood coagulation cascade Homo sapiens