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Literature summary 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

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

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.17.4.4 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

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

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.17.4.4 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

EC Number Organism UniProt Comment Textmining
1.17.4.4 Homo sapiens
-
-
-
4.1.1.90 Homo sapiens A7YA96
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.17.4.4 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
-
 ?
4.1.1.90 L-glutamate + CO2 + O2 + vitamin K hydroquinone
-
 Homo sapiens gamma-carboxy L-glutamate + vitamin K epoxide + H2O
-
 ir

Subunits

EC Number Subunits Comment Organism
4.1.1.90 heterodimer
-
 Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.17.4.4 vitamin K epoxide reductase
-
 Homo sapiens
1.17.4.4 VKOR
-
 Homo sapiens
1.17.4.4 VKORC1
-
 Homo sapiens
4.1.1.90 GGCX
-
 Homo sapiens
4.1.1.90 vitamin K carboxylase
-
 Homo sapiens
4.1.1.90 VKC
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
4.1.1.90 vitamin K
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.17.4.4 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
1.17.4.4 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
1.17.4.4 physiological function the enzyme is involved in the vitamin K cycle maintaining vitamin K levels and sustain the blood coagulation cascade Homo sapiens
4.1.1.90 physiological function VKC maintains vitamin K levels and sustains the blood coagulation cascade Homo sapiens