Vitamin K epoxide reductase complex subunit 1

Details

Name
Vitamin K epoxide reductase complex subunit 1
Synonyms
  • 1.17.4.4
  • Vitamin K1 2,3-epoxide reductase subunit 1
  • VKOR
Gene Name
VKORC1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001422|Vitamin K epoxide reductase complex subunit 1
MGSTWGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWG
RGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSVYL
AWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH
Number of residues
163
Molecular Weight
18234.3
Theoretical pI
9.58
GO Classification
Functions
quinone binding / vitamin-K-epoxide reductase (warfarin-sensitive) activity
Processes
blood coagulation / bone development / cellular protein metabolic process / drug metabolic process / peptidyl-glutamic acid carboxylation / post-translational protein modification / vitamin K metabolic process
Components
endoplasmic reticulum membrane / integral component of membrane
General Function
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.
Pfam Domain Function
Transmembrane Regions
9-29 75-95 101-123 127-149
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0016184|Vitamin K epoxide reductase complex subunit 1 (VKORC1)
ATGGGCAGCACCTGGGGGAGCCCTGGCTGGGTGCGGCTCGCTCTTTGCCTGACGGGCTTA
GTGCTCTCGCTCTACGCGCTGCACGTGAAGGCGGCGCGCGCCCGGGACCGGGATTACCGC
GCGCTCTGCGACGTGGGCACCGCCATCAGCTGTTCGCGCGTCTTCTCCTCCAGGTGGGGC
AGGGGTTTCGGGCTGGTGGAGCATGTGCTGGGACAGGACAGCATCCTCAATCAATCCAAC
AGCATATTCGGTTGCATCTTCTACACACTACAGCTATTGTTAGGTTGCCTGCGGACACGC
TGGGCCTCTGTCCTGATGCTGCTGAGCTCCCTGGTGTCTCTCGCTGGTTCTGTCTACCTG
GCCTGGATCCTGTTCTTCGTGCTCTATGATTTCTGCATTGTTTGTATCACCACCTATGCT
ATCAACGTGAGCCTGATGTGGCTCAGTTTCCGGAAGGTCCAAGAACCCCAGGGCAAGGCT
AAGAGGCACTGA
Chromosome Location
16
Locus
16p11.2
External Identifiers
ResourceLink
UniProtKB IDQ9BQB6
UniProtKB Entry NameVKOR1_HUMAN
GenBank Protein ID40217983
GenBank Gene IDAY423044
GenAtlas IDVKORC1
HGNC IDHGNC:23663
General References
  1. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. [PubMed:14765194]
  2. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. [PubMed:14765195]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
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  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
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  7. Goodstadt L, Ponting CP: Vitamin K epoxide reductase: homology, active site and catalytic mechanism. Trends Biochem Sci. 2004 Jun;29(6):289-92. [PubMed:15276181]
  8. Pelz HJ, Rost S, Hunerberg M, Fregin A, Heiberg AC, Baert K, MacNicoll AD, Prescott CV, Walker AS, Oldenburg J, Muller CR: The genetic basis of resistance to anticoagulants in rodents. Genetics. 2005 Aug;170(4):1839-47. Epub 2005 May 6. [PubMed:15879509]
  9. Tie JK, Nicchitta C, von Heijne G, Stafford DW: Membrane topology mapping of vitamin K epoxide reductase by in vitro translation/cotranslocation. J Biol Chem. 2005 Apr 22;280(16):16410-6. Epub 2005 Feb 16. [PubMed:15716279]
  10. Rost S, Fregin A, Hunerberg M, Bevans CG, Muller CR, Oldenburg J: Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin. Thromb Haemost. 2005 Oct;94(4):780-6. [PubMed:16270630]
  11. Schulman S, Wang B, Li W, Rapoport TA: Vitamin K epoxide reductase prefers ER membrane-anchored thioredoxin-like redox partners. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15027-32. doi: 10.1073/pnas.1009972107. Epub 2010 Aug 9. [PubMed:20696932]
  12. Rishavy MA, Usubalieva A, Hallgren KW, Berkner KL: Novel insight into the mechanism of the vitamin K oxidoreductase (VKOR): electron relay through Cys43 and Cys51 reduces VKOR to allow vitamin K reduction and facilitation of vitamin K-dependent protein carboxylation. J Biol Chem. 2011 Mar 4;286(9):7267-78. doi: 10.1074/jbc.M110.172213. Epub 2010 Oct 26. [PubMed:20978134]
  13. Tie JK, Jin DY, Stafford DW: Human vitamin K epoxide reductase and its bacterial homologue have different membrane topologies and reaction mechanisms. J Biol Chem. 2012 Oct 5;287(41):33945-55. doi: 10.1074/jbc.M112.402941. Epub 2012 Aug 24. [PubMed:22923610]
  14. Wu S, Tie JK, Stafford DW, Pedersen LG: Membrane topology for human vitamin K epoxide reductase. J Thromb Haemost. 2014 Jan;12(1):112-4. doi: 10.1111/jth.12450. [PubMed:24406068]
  15. Watzka M, Geisen C, Bevans CG, Sittinger K, Spohn G, Rost S, Seifried E, Muller CR, Oldenburg J: Thirteen novel VKORC1 mutations associated with oral anticoagulant resistance: insights into improved patient diagnosis and treatment. J Thromb Haemost. 2011 Jan;9(1):109-18. doi: 10.1111/j.1538-7836.2010.04095.x. [PubMed:20946155]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00266DicoumarolapprovedyesinhibitorDetails
DB00498Phenindioneapproved, investigationalyesinhibitorDetails
DB00682WarfarinapprovedyesinhibitorDetails
DB00946Phenprocoumonapproved, investigationalyesinhibitorDetails
DB00170Menadioneapproved, nutraceuticalyescofactorDetails
DB01418Acenocoumarolapproved, investigationalyesinhibitorDetails
DB09332KappadioneapprovedunknownsubstrateDetails