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Information on EC 1.17.4.5 - vitamin-K-epoxide reductase (warfarin-insensitive) and Organism(s) Homo sapiens and UniProt Accession Q8N0U8

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IUBMB Comments
Vitamin K 2,3-epoxide is reduced to 3-hydroxy- (and 2-hydroxy-) vitamin K by 1,4-dithiothreitol, which is oxidized to a disulfide. Not inhibited by warfarin [cf. EC 1.17.4.4, vitamin-K-epoxide reductase (warfarin-sensitive)].
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This record set is specific for:
Homo sapiens
UNIPROT: Q8N0U8
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
vkorl1, vitamin ko reductase, vitamin k 2,3 epoxide reductase, non-vkor, vkor-like1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
vitamin K epoxide reductase-like1
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VKOR-like1
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reductase, vitamin K epoxide (warfarin-insensitive)
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vitamin K 2,3 epoxide reductase
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vitamin K epoxide reductase
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vitamin K epoxide reductase (warfarin-insensitive)
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vitamin KO reductase
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VKOR
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VKORC1L1
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
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oxidation
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reduction
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SYSTEMATIC NAME
IUBMB Comments
3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone:oxidized-dithiothreitol oxidoreductase
Vitamin K 2,3-epoxide is reduced to 3-hydroxy- (and 2-hydroxy-) vitamin K by 1,4-dithiothreitol, which is oxidized to a disulfide. Not inhibited by warfarin [cf. EC 1.17.4.4, vitamin-K-epoxide reductase (warfarin-sensitive)].
CAS REGISTRY NUMBER
COMMENTARY hide
97089-80-0
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
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
show the reaction diagram
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-
-
?
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
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
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
show the reaction diagram
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-
-
?
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
show the reaction diagram
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?
additional information
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
integral membrane protein
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
VKORL1, EC 1.1.4.2, is more highly conserved among vertebrates than its evolutionary relative VKOR, EC 1.1.4.1. The human paralogous proteins are 42-60% identical
metabolism
vitamin K cycle, overview
physiological function
vitamin K dependent oxidative protection is independent of VKOR inhibition by warfarin and GGCX inhibition by 2-chloro-vitamin K1, which indicates that vitamin K plays potential physiological roles outside of the realm of carboxylation. The hVKORL1 turnover rate for vitamin K 2,3-epoxide reductase activity is significantly slower than for hVKOR, EC 1.1.4.1. the physiological role for VKORL1 reduction of vitamin K 2,3-epoxide is minimal
additional information
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conserved loop cysteines in VKOR are not required for active site regeneration after each cycle of oxidation. Missense mutations identified in the VKOR coding region, especially hotspot mutation at position 139, lead to a VKOR molecule more resistant to warfarin inhibition, thus requiring higher therapeutic warfarin doses
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
VKORL_HUMAN
176
2
19836
Swiss-Prot
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
L128R
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the naturally occuring mutant shows significantly increased warfarin resistance, but its enzyme activity is 2fold higher compared to wild-type VKOR
W59L
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the naturally occuring mutant shows significantly increased warfarin resistance, but its enzyme activity is 2fold higher compared to wild-type VKOR
W59R
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the naturally occuring mutant shows significantly increased warfarin resistance, but its enzyme activity is similar to wild-type VKOR
additional information
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
the VKOR-like gene that encodes hVKORL1 that is found on chromosome 7, sequence comparisons
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Van Horn, W.D.
Structural and functional insights into human vitamin K epoxide reductase and vitamin K epoxide reductase-like1
Crit. Rev. Biochem. Mol. Biol.
48
357-372
2013
Homo sapiens (Q8N0U8), Homo sapiens
Manually annotated by BRENDA team
Tie, J.K.; Jin, D.Y.; Tie, K.; Stafford, D.W.
Evaluation of warfarin resistance using TALENs-mediated vitamin K epoxide reductase knockout HEK293 cells
J. Thromb. Haemost.
11
1556-1564
2013
Homo sapiens
Manually annotated by BRENDA team