1.17.4.4: vitamin-K-epoxide reductase (warfarin-sensitive)
This is an abbreviated version!
For detailed information about vitamin-K-epoxide reductase (warfarin-sensitive), go to the full flat file.
Word Map on EC 1.17.4.4
-
1.17.4.4
-
cyp2c9
-
anticoagulant
-
dosing
-
pharmacogenetic
-
bleeding
-
cyp4f2
-
thromboembolic
-
k-dependent
-
coagulation
-
acenocoumarol
-
interindividual
-
pharmacogenomics
-
fibrillation
-
gg
-
caucasian
-
prothrombin
-
atrial
-
demographic
-
pharmacodynamics
-
clot
-
valve
-
ethnic
-
thrombosis
-
genotype-guided
-
s-warfarin
-
rodenticides
-
gamma-glutamyl
-
non-genetic
-
phenprocoumon
-
warfarin-treated
-
4-hydroxycoumarins
-
gamma-carboxylase
-
coumadin
-
pharmacogenes
-
medicine
-
pivka-ii
-
slco1b1
-
calumenin
-
amiodarone
-
genotype-based
-
interpatient
-
cyp3a5
-
hypoprothrombinemia
-
undercarboxylated
-
clopidogrel
-
antivitamin
-
gamma-carboxylation
- 1.17.4.4
- cyp2c9
-
anticoagulant
-
dosing
-
pharmacogenetic
-
bleeding
- cyp4f2
-
thromboembolic
-
k-dependent
-
coagulation
-
acenocoumarol
-
interindividual
-
pharmacogenomics
- fibrillation
- gg
-
caucasian
- prothrombin
- atrial
-
demographic
-
pharmacodynamics
- clot
- valve
-
ethnic
- thrombosis
-
genotype-guided
-
s-warfarin
-
rodenticides
-
gamma-glutamyl
-
non-genetic
- phenprocoumon
-
warfarin-treated
- 4-hydroxycoumarins
- gamma-carboxylase
-
coumadin
-
pharmacogenes
- medicine
-
pivka-ii
-
slco1b1
- calumenin
- amiodarone
-
genotype-based
-
interpatient
- cyp3a5
- hypoprothrombinemia
-
undercarboxylated
- clopidogrel
-
antivitamin
-
gamma-carboxylation
Reaction
Synonyms
EC 1.1.4.1, phylloquinone epoxide reductase, reductase, phylloquinone epoxide, vitamin K 2,3-epoxide reductase, vitamin K 2,3-epoxide reductase complex subunit 1, vitamin K 2,3-epoxide reductase complex subunit-1, vitamin K epoxid reductase, vitamin K epoxide reductase, vitamin K epoxide reductase complex subunit 1, vitamin K oxidoreductase, Vitamin K reductase, vitamin K-2,3-epoxide reductase, vitamin K-2,3-epoxide reductase subunit 1, vitamin K-epoxide reductase, vitamin K1 epoxide reductase, vitaminK epoxide reductase, VKOR, VKOR complex, VKORC1, VKORC1 variant 2, VKORC1-like 1, VKORC1L1, VKORC1v2, warfarin sensitive vitamin K 2,3-epoxide reductase, warfarin-sensitive vitamin K1 2,3-epoxide reductase
ECTree
1.17.4.4 vitamin-K-epoxide reductase (warfarin-sensitive)Advanced search results
results (
results (Natural Substrates Products
Natural Substrates Products on EC 1.17.4.4 - vitamin-K-epoxide reductase (warfarin-sensitive)
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
NATURAL SUBSTRATE 
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide
i.e. vitamin K
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide
i.e. vitamin K, an important cofactor for the posttranslational gamma-carboxylation of several blood coagulation factors
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide, the enzyme initiates the vitamin K catalytic cycle, overview
i.e. vitamin K
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide
i.e. vitamin K
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide
i.e. vitamin K
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide
i.e. vitamin K
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
i.e. vitamin K 2,3-epoxide
i.e. vitamin K
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide
i.e. vitamin K
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
i.e. vitamin K 2,3-epoxide, the enzyme is supposed to catalyze the reduction of the epoxide to quinone and of the quinone to vitamin K hydroquinone
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
2-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone + oxidized dithiothreitol
-
-
-
?
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
-
r
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
-
r
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
-
r
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
-
r
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
?, r
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
-
r
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
-
r
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol + H2O
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol
-
-
-
-
r
2,3-epoxyphylloquinone + AH2
phylloquinone + A + ?
-
VKOR reduces vitamin K using membrane-embedded thiols, Cys132 and Cys135, which become oxidized with concomitant VKOR inactivation. VKOR is subsequently reactivated by an unknown redox protein that might act directly on the Cys132-Cys135 residues
-
-
?
2,3-epoxyphylloquinone + AH2
phylloquinone + A + ?
the enzyme catalyzes the reduction of vitamin K 2,3-epoxide to vitamin K1, overview
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
r
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
r
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
r
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
r
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
r
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
r
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
r
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
reduction of vitamin K 2,3-epoxide to vitamin K
-
-
?
2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
-
-
-
r
vitamin K 2,3-epoxide + dithiothreitol
vitamin K + oxidized dithiothreitol
-
-
-
?
vitamin K 2,3-epoxide + dithiothreitol
vitamin K + oxidized dithiothreitol
-
-
-
-
?
vitamin K 2,3-epoxide + dithiothreitol
vitamin K + oxidized dithiothreitol
-
thioredoxin is the possible physiological electron acceptor
-
?
vitamin K 2,3-epoxide + dithiothreitol
vitamin K + oxidized dithiothreitol
-
reaction in metabolic pathway of vitamin K
-
?
vitamin K 2,3-epoxide + dithiothreitol
vitamin K + oxidized dithiothreitol
-
reaction in metabolic pathway of vitamin K
-
?
vitamin K 2,3-epoxide + dithiothreitol
vitamin K + oxidized dithiothreitol
-
thioredoxin is the possible physiological electron acceptor
-
?
vitamin K1 2,3-epoxide + dithiothreitol
vitamin K1 + oxidized dithiothreitol
-
two patients suffering from combined deficiency of vitamin K-dependent clotting factors type 2 possess a R98W substitution at the presumed cytoplasmic end of TM alpha-helix 2. Because the residue is far-removed from the proposed active site its mutation is, therefore assumed to disrupt VKORC1 structure or VKOR complex assembly rather than catalysis
-
-
?
vitamin K1 2,3-epoxide + dithiothreitol
vitamin K1 + oxidized dithiothreitol
VKORC1 contains missense mutations in the two heritable human diseases: combined deficiency of vitamin-K-dependent clotting factors type 2 (VKCFD2, Online Mendelian Inheritance in Man 607473) and resistance to coumarin-type anticoagulant drugs (warfarin resistance, WR, Online Mendelian Inheritance in man 122700)
-
-
?
vitamin K1 2,3-epoxide + dithiothreitol
vitamin K1 + oxidized dithiothreitol
-
vitamin K is an essential cofactor for post-translational gamma-carboxylation of vitamin K-dependent coagulation factors. The modification is carried out by a system of integral proteins of the endoplasmic reticulum membrane where the warfarin sensitive vitamin K 2,3-epoxide reductase (VKOR) produces the reduced hydroquinone form of vitamin K needed by the gamma-carboxylase as the active cofactor. VKOR is the rate-limiting step in the system
-
-
?
additional information
?
-
-
VKOR is a part of the post-translational protein-modification system that produces gamma-carboxylated proteins. The vitamin K-dependent gamma-carboxylation system consists of the vitamin K-dependent gamma-carboxylase, which requires the reduced hydroquinone form of vitamin K1 as a cofactor and the warfarin-sensitive enzyme vitamin K1 2,3-epoxide reductase, VKOR. VKOR and gamma-carboxylase are close enough together in the membrane to operate as a supramolecular assembly of proteins, in which substrates and products are shuttled efficiently from one component to the next. Calumenin is likely to have a regulatory role in controlling the activity of the system
-
-
?
additional information
?
-
-
the enzyme is involved in coagulation factor activity
-
-
?
additional information
?
-
the enzyme is involved in coagulation factor activity
-
-
?
additional information
?
-
-
the enzyme is involved in reduction of vitamin K, which is required by the gamma-glutamyl carboxylase, GGCX, transforming glutamate to gamma carboxyl glutamic acid in a vitamin K-dependent manner, gamma carboxyl glutamic acid is required for activity of proteins involved in coagulation, overview
-
-
?
additional information
?
-
-
the enzyme is involved in regulation of response to oral anticoagulants of European-American warfarin patients
-
-
?
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
-
-
?
additional information
?
-
vitamin K epoxide reductase is the enzyme responsible for the recycling of vitamin K 2,3-epoxide to vitamin K hydroquinone, a cofactor that is essential for the synthesis of several blood coagulation factors
-
-
?
additional information
?
-
-
VKORC1 is the key gene of the vitamin K cycle encoding the molecular target of coumarin-type anticoagulants vitaminK epoxide reductase, VKORC1 recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, which functions as the essential cofactor for gamma-carboxylation of gamma-carboxyl-glutamic acid-domain proteins such as coagulation factors II, VII, IX, and X, proteins C, S, and Z, osteocalcin, matrix Gla protein MGP, and Gas6, gamma-glutamyl carboxylase, GGCX, is the enzyme that accomplishes the carboxylation reaction, VKORC1 represents the rate-limiting step in the reaction
-
-
?
additional information
?
-
-
the enzyme, driven by the reducing agent DTT, reduces both vitamin K 2,3-epoxide and vitamin K to the activated hydroquinone form
-
-
?
additional information
?
-
-
VKOR is a part of the post-translational protein-modification system that produces gamma-carboxylated proteins. The vitamin K-dependent gamma-carboxylation system consists of the vitamin K-dependent gamma-carboxylase, which requires the reduced hydroquinone form of vitamin K1 as a cofactor and the warfarin-sensitive enzyme vitamin K1 2,3-epoxide reductase, VKOR. VKOR and gamma-carboxylase are close enough together in the membrane to operate as a supramolecular assembly of proteins, in which substrates and products are shuttled efficiently from one component to the next. Calumenin is likely to have a regulatory role in controlling the activity of the system
-
-
?
additional information
?
-
-
the reduction is linked to dithiol-dependent oxidative folding of proteins in the ER by protein disulfide isomerase, PDI, oxidative folding of reduced RNase triggers the reduction of vitamin K epoxid and the gamma-carboxylation of the synthetic gamma-carboxylase peptide substrate FLEEL, overview
-
-
?
