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Literature summary extracted from

  • Oldenburg, J.; Bevans, C.G.; Mueller, C.R.; Watzka, M.
    Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle (2006), Antioxid. Redox Signal., 8, 347-353.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.17.4.4
-
 Mus musculus
1.17.4.4 gene VKORC1, located on chromosome 1, DNA and amino acid sequenc determination and analysis, expression of wild-type and warfarin-resistant mutant enzymes in HEK-293 cells, expression of the latter alomost completely abolishes the enzyme activity Rattus norvegicus
1.17.4.4 gene VKORC1, located on chromosome 16, DNA and amino acid sequenc determination and analysis, genetic structure, expression in Spodoptera frugiperda Sf9 cells and in Pichia pastoris Homo sapiens
1.17.4.4 gene VKORC1, located on chromosome 7, DNA and amino acid sequenc determination and analysis Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
1.17.4.4 additional information allelic mutations in the orthologous gene can cause warfarin resistance Rattus norvegicus
1.17.4.4 additional information allelic mutations in the orthologous gene of VKORC1 can cause warfarin resistance Mus musculus
1.17.4.4 additional information deficient enzyme mutants cause VKCFD2 disease phenotype Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.17.4.4 phenprocoumon 4-hydroxycoumarin-derived anticoagulation drug, blocks the recycling of vitamin K epoxid inhibiting the two dithiol-dependent steps performed by the enzyme Homo sapiens
1.17.4.4 phenprocoumon
-
 Mus musculus
1.17.4.4 phenprocoumon
-
 Rattus norvegicus
1.17.4.4 warfarin 4-hydroxycoumarin-derived anticoagulation drug, blocks the recycling of vitamin K epoxid inhibiting the two dithiol-dependent steps performed by the enzyme Homo sapiens
1.17.4.4 warfarin
-
 Mus musculus
1.17.4.4 warfarin
-
 Rattus norvegicus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.17.4.4 endoplasmic reticulum membrane membrane topology, overview Mus musculus 5789
-
1.17.4.4 endoplasmic reticulum membrane membrane topology, overview Rattus norvegicus 5789
-
1.17.4.4 endoplasmic reticulum membrane the enzyme possesses 3 or 4 transmembrane alpha-helices and a large cytoplasmic loop, membrane topology, overview Homo sapiens 5789
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.17.4.4 18000
-
 x * 18000 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.17.4.4 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol Mus musculus i.e. vitamin K 2,3-epoxide 2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol i.e. vitamin K ?
1.17.4.4 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol Homo sapiens i.e. vitamin K 2,3-epoxide 2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol i.e. vitamin K ?
1.17.4.4 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol Rattus norvegicus i.e. vitamin K 2,3-epoxide 2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol i.e. vitamin K ?
1.17.4.4 additional information Homo sapiens the VKCFD2 disease, a vitamin K-dependent clotting factor deficiency, is caused by enzyme mutations, VKORC1 is the key component of the vitamin K reductase activity targeted by coumarin-derived drugs in prophylaxis and therapy of thrombosis ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.17.4.4 Homo sapiens
-
 gene VKORC1
-
1.17.4.4 Mus musculus
-
 gene VKORC1
-
1.17.4.4 Rattus norvegicus
-
 gene VKORC1
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.17.4.4 phylloquinone + a protein with a disulfide bond + H2O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues protein structure and catalytic mechanism, the enzyme activity is rate-limiting for the following gamma-carboxylation step Mus musculus
a
1.17.4.4 phylloquinone + a protein with a disulfide bond + H2O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues protein structure and catalytic mechanism, the enzyme activity is rate-limiting for the following gamma-carboxylation step Homo sapiens
a
1.17.4.4 phylloquinone + a protein with a disulfide bond + H2O = 2,3-epoxyphylloquinone + a protein with reduced L-cysteine residues protein structure and catalytic mechanism, the enzyme activity is rate-limiting for the following gamma-carboxylation step Rattus norvegicus
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.17.4.4 heart fetal and adult Homo sapiens
-
1.17.4.4 kidney
-
 Mus musculus
-
1.17.4.4 kidney
-
 Rattus norvegicus
-
1.17.4.4 kidney fetal Homo sapiens
-
1.17.4.4 liver
-
 Mus musculus
-
1.17.4.4 liver
-
 Rattus norvegicus
-
1.17.4.4 liver fetal and adult Homo sapiens
-
1.17.4.4 lung fetal Homo sapiens
-
1.17.4.4 pancreas adult Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.17.4.4 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol i.e. vitamin K 2,3-epoxide Mus musculus 2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol i.e. vitamin K ?
1.17.4.4 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol i.e. vitamin K 2,3-epoxide Homo sapiens 2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol i.e. vitamin K ?
1.17.4.4 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol i.e. vitamin K 2,3-epoxide Rattus norvegicus 2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol i.e. vitamin K ?
1.17.4.4 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol i.e. vitamin K 2,3-epoxide, two dithiol-dependent steps Homo sapiens 2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol i.e. vitamin K ?
1.17.4.4 additional information the VKCFD2 disease, a vitamin K-dependent clotting factor deficiency, is caused by enzyme mutations, VKORC1 is the key component of the vitamin K reductase activity targeted by coumarin-derived drugs in prophylaxis and therapy of thrombosis Homo sapiens ?
-
 ?

Subunits

EC Number Subunits Comment Organism
1.17.4.4 ? x * 18000 Homo sapiens
1.17.4.4 More the enzyme possesses a dicoumarol binding hydrophobic sequence motif TYA, VKOR complex structure, overview Homo sapiens
1.17.4.4 More VKOR complex structure, overview Mus musculus
1.17.4.4 More VKOR complex structure, overview Rattus norvegicus

Synonyms

EC Number Synonyms Comment Organism
1.17.4.4 vitamin K epoxide reductase
-
 Mus musculus
1.17.4.4 vitamin K epoxide reductase
-
 Homo sapiens
1.17.4.4 vitamin K epoxide reductase
-
 Rattus norvegicus
1.17.4.4 vitamin K epoxide reductase complex subunit 1
-
 Mus musculus
1.17.4.4 vitamin K epoxide reductase complex subunit 1
-
 Homo sapiens
1.17.4.4 vitamin K epoxide reductase complex subunit 1
-
 Rattus norvegicus
1.17.4.4 VKOR
-
 Mus musculus
1.17.4.4 VKOR
-
 Homo sapiens
1.17.4.4 VKOR
-
 Rattus norvegicus
1.17.4.4 VKORC1
-
 Mus musculus
1.17.4.4 VKORC1
-
 Homo sapiens
1.17.4.4 VKORC1
-
 Rattus norvegicus

pI Value

EC Number Organism Comment pI Value Maximum pI Value
1.17.4.4 Homo sapiens sequence calculation
-
 10.7