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Literature summary extracted from

  • 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 (2013), J. Thromb. Haemost., 11, 1556-1564.
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
1.17.4.4 additional information knockout of endogenous VKOR activity, i.e. VKOR and VKORC1L1 enzymes, in HEK-293 cells by transcription activator-like effector nucleases (TALENs)-mediated genome editing, overview. VKOR knockout cells regained KO reductase activity through VKORC1L1 after culturing for several generations (Figure 3A). In addition, this activity is sensitive to warfarin inhibition as the wild-type cells Homo sapiens
1.17.4.5 L128R the naturally occuring mutant shows significantly increased warfarin resistance, but its enzyme activity is 2fold higher compared to wild-type VKOR Homo sapiens
1.17.4.5 additional information knockout of endogenous VKOR activity, i.e. VKOR and VKORC1L1 enzymes, in HEK-293 cells by transcription activator-like effector nucleases (TALENs)-mediated genome editing, overview Homo sapiens
1.17.4.5 additional information the W59R mutant has lower activity but higher warfarin resistance than the W59L mutant, warfarin resistance evaluation of the naturally occurring VKOR mutants, overview Homo sapiens
1.17.4.5 W59L the naturally occuring mutant shows significantly increased warfarin resistance, but its enzyme activity is 2fold higher compared to wild-type VKOR Homo sapiens
1.17.4.5 W59R the naturally occuring mutant shows significantly increased warfarin resistance, but its enzyme activity is similar to wild-type VKOR Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.17.4.4 warfarin the oral anticoagulant impairs the synthesis of functional clotting factors through inhibition of VKOR and is widely used for prevention and treatment of thrombosis Homo sapiens
1.17.4.5 additional information evaluation of warfarin resistance using TALENs-mediated vitamin K epoxide reductase knockout HEK293 cells, overview 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-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol Homo sapiens
-
 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
 ?
1.17.4.5 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
-
-
-
1.17.4.5 Homo sapiens
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.17.4.4 HEK-293 cell
-
 Homo sapiens
-
1.17.4.5 HEK-293 cell
-
 Homo sapiens
-

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
-
 Homo sapiens 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
-
 ?
1.17.4.5 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
-
 ?

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 VKORC1L1
-
 Homo sapiens
1.17.4.5 vitamin K epoxide reductase
-
 Homo sapiens
1.17.4.5 VKOR
-
 Homo sapiens
1.17.4.5 VKORC1L1
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.17.4.4 additional information conserved loop cysteines in VKOR are not required for active site regeneration after each cycle of oxidation Homo sapiens
1.17.4.5 additional information 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 Homo sapiens