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Literature summary extracted from
- Structural and functional insights into human vitamin K epoxide reductase and vitamin K epoxide reductase-like1 (2013), Crit. Rev. Biochem. Mol. Biol., 48, 357-372.
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 1.17.4.4 | gene Vkor, sequence comparisons | Homo sapiens |
| 1.17.4.5 | the VKOR-like gene that encodes hVKORL1 that is found on chromosome 7, sequence comparisons | Homo sapiens |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 1.17.4.4 | C43A | naturally occuring mutant, active in presence of DTT, which helps to bypass C43 | Homo sapiens |
| 1.17.4.4 | C51A | naturally occuring mutant, active in presence of DTT, which helps to bypass C43 | Homo sapiens |
| 1.17.4.4 | I123N | naturally occuring mutant | Homo sapiens |
| 1.17.4.4 | R58G | naturally occuring mutant | Homo sapiens |
| 1.17.4.4 | W59R/W59C/W59L | naturally occuring mutant | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.17.4.4 | warfarin | hVKOR is directly and irreversibly inhibited by warfarin, hVKOR is the target of a common anticoagulant, warfarin. Tyr139 in hVKOR is part of the warfarin binding site | Homo sapiens |  |
| 1.17.4.4 | warfarin | - |
Mycobacterium tuberculosis | |
| 1.17.4.5 | additional information | non-VKOR, warfarin-sensitive enzyme, while hVKORL is mainly insensitive to inhibition by warfarin, but about 30% of hVKORL1 is inhibited by 0.005 mM warfarin, VKORL1 is warfarin sensitive, but not affect warfarin dosage requirements | Homo sapiens |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.17.4.4 | endoplasmic reticulum membrane | integral membrane protein, topology, overview | Homo sapiens | 5789 | - |
| 1.17.4.5 | endoplasmic reticulum membrane | integral membrane protein | Homo sapiens | 5789 | - |
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 + H2O | Homo sapiens | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
? | |
| 1.17.4.4 | 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | Mycobacterium tuberculosis | - |
2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
? | |
| 1.17.4.4 | additional information | Homo sapiens | the enzyme, driven by the reducing agent DTT, reduces both vitamin K 2,3-epoxide and vitamin K to the activated hydroquinone form | ? | - |
? | |
| 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 | - |
? | |
| 1.17.4.5 | additional information | Homo sapiens | the enzyme, driven by the reducing agent DTT, reduces both vitamin K 2,3-epoxide and vitamin K to the activated hydroquinone form | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.17.4.4 | Homo sapiens | - |
- |
- |
| 1.17.4.4 | Mycobacterium tuberculosis | - |
- |
- |
| 1.17.4.5 | Homo sapiens | Q8N0U8 | - |
- |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.17.4.4 | liver | high expression level | Homo sapiens | - |
| 1.17.4.5 | HEK-293T 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 + H2O | - |
Homo sapiens | 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
? | |
| 1.17.4.4 | 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol + H2O | - |
Mycobacterium tuberculosis | 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol | - |
? | |
| 1.17.4.4 | 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 | Homo sapiens | ? | - |
? | |
| 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 | - |
? | |
| 1.17.4.5 | 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 | Homo sapiens | ? | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.17.4.4 | vitamin K epoxide reductase | - |
Homo sapiens |
| 1.17.4.4 | vitamin K epoxide reductase | - |
Mycobacterium tuberculosis |
| 1.17.4.4 | VKOR | - |
Homo sapiens |
| 1.17.4.4 | VKOR | - |
Mycobacterium tuberculosis |
| 1.17.4.4 | VKOR complex | - |
Homo sapiens |
| 1.17.4.4 | VKOR complex | - |
Mycobacterium tuberculosis |
| 1.17.4.4 | VKORC1 | - |
Homo sapiens |
| 1.17.4.5 | non-VKOR | - |
Homo sapiens |
| 1.17.4.5 | vitamin K epoxide reductase-like1 | - |
Homo sapiens |
| 1.17.4.5 | VKOR-like1 | - |
Homo sapiens |
| 1.17.4.5 | VKORL1 | - |
Homo sapiens |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.17.4.4 | evolution | the enzyme belongs to the thiol-disulfide oxidoreductases. 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% identical with 60% similarity | Homo sapiens |
| 1.17.4.4 | malfunction | warfarin interfers with the vitamin K cycle by inhibiting VKOR thus limiting the available activated hydroquinone cofactor and functionally impeding various blood clotting proteins that are dependent on gamma-carboxyglutamate residues | Homo sapiens |
| 1.17.4.4 | metabolism | vitamin K cycle, overview | Homo sapiens |
| 1.17.4.4 | additional information | structure-function relationship, the CXXC redox center active site (hVKOR Cys132 and Cys135) is located in the final transmembrane helix near the endoplasmic reticulum lumen/periplasmic side of the membrane, overview | Homo sapiens |
| 1.17.4.4 | physiological function | vitamin K dependent oxidative protection is independent of VKOR inhibition by warfarin and GGCX inhibition by 2-chloro-vitamin K1, which indicated that vitamin K plays potential physiological roles outside of the realm of carboxylation. The hVKORL1, EC 11.4.2, turnover rate for vitamin K 2,3-epoxide reductase activity is significantly slower than for hVKOR | Homo sapiens |
| 1.17.4.5 | 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 | Homo sapiens |
| 1.17.4.5 | metabolism | vitamin K cycle, overview | Homo sapiens |
| 1.17.4.5 | 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 | Homo sapiens |
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