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Literature summary for 1.17.4.4 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)

Cloned (Comment) Organism
-
Mus musculus
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
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
gene VKORC1, located on chromosome 7, DNA and amino acid sequenc determination and analysis Mus musculus

Protein Variants

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

Inhibitors

Inhibitors Comment Organism Structure
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
phenprocoumon
-
Mus musculus
phenprocoumon
-
Rattus norvegicus
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
warfarin
-
Mus musculus
warfarin
-
Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
endoplasmic reticulum membrane membrane topology, overview Mus musculus 5789
-
endoplasmic reticulum membrane membrane topology, overview Rattus norvegicus 5789
-
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]

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

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
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 ?
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 ?
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 ?
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

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

Reaction

Reaction Comment Organism Reaction ID
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
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
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

Source Tissue

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

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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 ?
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 ?
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 ?
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 ?
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

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

Synonyms

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

pI Value

Organism Comment pI Value Maximum pI Value
Homo sapiens sequence calculation
-
10.7