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Showing drug card for Warfarin (DB00682)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:54
Primary Accession Number DB00682
Secondary Accession Number
  • APRD00341
Name Warfarin
Drug Type
  • Approved
  • Small Molecule
Description An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [PubChem]
Synonyms
  1. Warfarin sodium
Brand Names
  1. Athrombin
  2. Athrombin-K
  3. Athrombine-K
  4. Brumolin
  5. Co-Rax
  6. Coumadin
  7. Coumafen
  8. Coumafene
  9. Coumaphen
  10. Coumaphene
  11. Coumarins
  12. Coumefene
  13. D-Con
  14. Dethmor
  15. Dethnel
  16. Dicusat E
  17. Frass-Ratron
  18. Jantoven
  19. Kumader
  20. Kumadu
  21. Kumatox
  22. Kypfarin
  23. Latka 42
  24. Mar-Frin
  25. Marevan
  26. Maveran
  27. Panwarfin
  28. Place-Pax
  29. Prothromadin
  30. RAX
  31. Rosex
  32. Sofarin
  33. Solfarin
  34. Sorexa Plus
  35. Temus W
  36. Tintorane
  37. Tox-Hid
  38. Vampirinip II
  39. Vampirinip III
  40. Waran
  41. Warf 42
  42. Warfarat
  43. Warfarin Plus
  44. Warfarin Q
  45. Warfarine
  46. Warficide
  47. Warfilone
  48. Zoocoumarin
Brand Mixtures Not Available
Chemical IUPAC Name 2-hydroxy-3-(3-oxo-1-phenylbutyl)chromen-4-one
Chemical Formula C19H16O4
Chemical Structure Structure
CAS Registry Number 81-81-2
InChI Identifier InChI=1/C19H16O4/c1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22/h2-10,15,22H,11H2,1H3
InChI Key QTXVAVXCBMYBJW-UHFFFAOYAL
KEGG Drug Not Available
KEGG Compound C01541 Link Image
PubChem Compound 6691 Link Image
PubChem Substance 4702 Link Image
ChEBI ID Not Available
PharmGKB ID PA451906 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02244463 Link Image
RxList Link http://www.rxlist.com/cgi/generic/warfarin.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Warfarin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Stahmann, et al., U.S. Pat. 2,427,578 (1947)
Average Molecular Weight 308.3279
Monoisotopic Molecular Weight 308.1049
State Solid
Melting Point 161 oC
Experimental Water Solubility 17 mg/L Source: PhysProp
Predicted Water Solubility 4.77e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3 Source: PhysProp
Predicted LogP 2.55 Calculated using ALOGPS
Experimental LogS -3.89 [ADME Research, USCD]
Predicted LogS -3.81 Calculated using ALOGPS
Experimental Caco2 Permeability -4.68 [ADME Research, USCD]
pKa/Isoelectric Point 5.08
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(=O)C[C@@H](C1=CC=CC=C1)C1=C(O)OC2=CC=CC=C2C1=O
Canonical SMILES CC(=O)CC(C1=CC=CC=C1)C1=C(O)OC2=CC=CC=C2C1=O
Drug Category
  • Anticoagulants
  • Coumarin and Indandione Derivatives
  • Rodenticides
ATC Codes
AHFS Codes
  • 20:12.04.08
Indication For the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis.
Pharmacology Warfarin, a coumarin anticoagulant, is a racemic mixture of two active isomers. It is used in the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF).
Mechanism of Action Warfarin inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Absorption Not Available
Toxicity LD50=374 (orally in mice)
Protein Binding 99.5%
Biotransformation Metabolized by hepatic microsomal enzymes.
Half Life 1 week
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions
  • Avoid St.John's Wort.
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Consult your doctor before taking large amounts of Vitamin K (Green leafy vegetables).
  • Limit garlic, ginger, gingko, and horse chestnut.
Pathways
Name SMPDB Link KEGG Link
Warfarin Pathway SMP00268 Link Image
General References
  1. Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. [PubMed Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. [PubMed Link Image]
  5. Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. [PubMed Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 1A2 (CYP1A2)
  2. Cytochrome P450 2C8 (CYP2C8)
  3. Cytochrome P450 2C9 (CYP2C9)
Targets
  1. Prothrombin
  2. Vitamin K epoxide reductase complex subunit 1
  3. Vitamin K epoxide reductase complex subunit 1-like protein 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 1 Gene Name CYP1A2
Enzyme 1 SwissProt ID P05177 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human). 
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2C8 (CYP2C8)
Enzyme 2 Gene Name CYP2C8
Enzyme 2 SwissProt ID P10632 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P10632|CP2C8_HUMAN Cytochrome P450 2C8 (EC 1.14.14.1) 
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKV
YGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRW
KEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICS
VVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALT
RSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTE
TTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSD
LVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFK
KSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLP
PSYQICFIPV
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 3 Gene Name CYP2C9
Enzyme 3 SwissProt ID P11712 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Drug Target 1 [top]
Target 1 ID 54
Target 1 Name Prothrombin
Target 1 Synonyms
  1. Activated Factor II [IIa]
  2. Coagulation factor II
  3. EC 3.4.21.5
  4. Prothrombin precursor
  5. Thrombin
Target 1 Gene Name F2
Target 1 Protein Sequence >Prothrombin precursor 
MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLEREC
VEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHV
NITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQE
CSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASA
QAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETG
DGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYI
DGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTEN
DLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHP
VCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDST
RIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKY
GFYTHVFRLKKWIQKVIDQFGE
Target 1 Number of Residues 632
Target 1 Molecular Weight 70037
Target 1 Theoretical pI 5.70
Target 1 GO Classification
Function
thrombin activity
binding
ion binding
cation binding
calcium ion binding
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
serine-type endopeptidase activity
Process
organismal physiological process
regulation of body fluids
hemostasis
blood coagulation
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
extracellular region
Target 1 General Function Involved in blood clotting cascade
Target 1 Specific Function Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C
Target 1 Pathways Not Available
Target 1 Reactions
  • Selective cleavage of Arg!Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B INHIBITOR Benzamidine; D-Phe-Pro-Arg-CH2Cl; Nalpha-(2-naphthyl-sulfonyl-glycyl)-D-p-amidinopheyl-alanylpiperadin e; Argatroban
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-24
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 339641 Link Image
Target 1 UniProtKB/Swiss-Prot ID P00734 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name THRB_HUMAN Link Image
Target 1 PDB ID 1HAG Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Secreted protein
  • extracellular space
Target 1 Gene Sequence >1869 bp 
ATGGCGCACGTCCGAGGCTTGCAGCTGCCTGGCTGCCTGGCCCTGGCTGCCCTGTGTAGC
CTTGTGCACAGCCAGCATGTGTTCCTGGCTCCTCAGCAAGCACGGTCGCTGCTCCAGCGG
GTCCGGCGAGCCAACACCTTCTTGGAGGAGGTGCGCAAGGGCAACCTAGAGCGAGAGTGC
GTGGAGGAGACGTGCAGCTACGAGGAGGCCTTCGAGGCTCTGGAGTCCTCCACGGCTACG
GATGTGTTCTGGGCCAAGTACACAGCTTGTGAGACAGCGAGGACGCCTCGAGATAAGCTT
GCTGCATGTCTGGAAGGTAACTGTGCTGAGGGTCTGGGTACGAACTACCGAGGGCATGTG
AACATCACCCGGTCAGGCATTGAGTGCCAGCTATGGAGGAGTCGCTACCCACATAAGCCT
GAAATCAACTCCACTACCCATCCTGGGGCCGACCTACAGGAGAATTTCTGCCGCAACCCC
GACAGCAGCACCACGGGACCCTGGTGCTACACTACAGACCCCACCGTGAGGAGGCAGGAA
TGCAGCATCCCTGTCTGTGGCCAGGATCAAGTCACTGTAGCGATGACTCCACGCTCCGAA
GGCTCCAGTGTGAATCTGTCACCTCCATTGGAGCAGTGTGTCCCTGATCGGGGGCAGCAG
TACCAGGGGCGCCTGGCGGTGACCACACATGGGCTCCCCTGCCTGGCCTGGGCCAGCGCA
CAGGCCAAGGCCCTGAGCAAGCACCAGGACTTCAACTCAGCTGTGCAGCTGGTGGAGAAC
TTCTGCCGCAACCCAGACGGGGATGAGGAGGGCGTGTGGTGCTATGTGGCCGGGAAGCCT
GGCGACTTTGGGTACTGCGACCTCAACTATTGTGAGGAGGCCGTGGAGGAGGAGACAGGA
GATGGGCTGGATGAGGACTCAGACAGGGCCATCGAAGGGCGTACCGCCACCAGTGAGTAC
CAGACTTTCTTCAATCCGAGGACCTTTGGCTCGGGAGAGGCAGACTGTGGGCTGCGACCT
CTGTTCGAGAAGAAGTCGCTGGAGGACAAAACCGAAAGAGAGCTCCTGGAATCCTACATC
GACGGGCGCATTGTGGAGGGCTCGGATGCAGAGATCGGCATGTCACCTTGGCAGGTGATG
CTTTTCCGGAAGAGTCCCCAGGAGCTGCTGTGTGGGGCCAGCCTCATCAGTGACCGCTGG
GTCCTCACCGCCGCCCACTGCCTCCTGTACCCGCCCTGGGACAAGAACTTCACCGAGAAT
GACCTTCTGGTGCGCATTGGCAAGCACTCCCGCACAAGGTACGAGCGAAACATTGAAAAG
ATATCCATGTTGGAAAAGATCTACATCCACCCCAGGTACAACTGGCGGGAGAACCTGGAC
CGGGACATTGCCCTGATGAAGCTGAAGAAGCCTGTTGCCTTCAGTGACTACATTCACCCT
GTGTGTCTGCCCGACAGGGAGACGGCAGCCAGCTTGCTCCAGGCTGGATACAAGGGGCGG
GTGACAGGCTGGGGCAACCTGAAGGAGACGTGGACAGCCAACGTTGGTAAGGGGCAGCCC
AGTGTCCTGCAGGTGGTGAACCTGCCCATTGTGGAGCGGCCGGTCTGCAAGGACTCCACC
CGGATCCGCATCACTGACAACATGTTCTGTGCTGGTTACAAGCCTGATGAAGGGAAACGA
GGGGATGCCTGTGAAGGTGACAGTGGGGGACCCTTTGTCATGAAGAGCCCCTTTAACAAC
CGCTGGTATCAAATGGGCATCGTCTCATGGGGTGAAGGCTGTGACCGGGATGGGAAATAT
GGCTTCTACACACATGTGTTCCGCCTGAAGAAGTGGATACAGAAGGTCATTGATCAGTTT
GGAGAGTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID F2 Link Image
Target 1 GenAtlas ID F2 Link Image
Target 1 HGNC ID HGNC:3535 Link Image
Target 1 Chromosome Location 11
Target 1 Locus 11p11-q12
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Guinto ER, Caccia S, Rose T, Futterer K, Waksman G, Di Cera E: Unexpected crucial role of residue 225 in serine proteases. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1852-7. [PubMed Link Image]
  2. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  3. Iwahana H, Yoshimoto K, Shigekiyo T, Shirakami A, Saito S, Itakura M: Detection of a single base substitution of the gene for prothrombin Tokushima. The application of PCR-SSCP for the genetic and molecular analysis of dysprothrombinemia. Int J Hematol. 1992 Feb;55(1):93-100. [PubMed Link Image]
  4. Miyata T, Aruga R, Umeyama H, Bezeaud A, Guillin MC, Iwanaga S: Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity. Biochemistry. 1992 Aug 25;31(33):7457-62. [PubMed Link Image]
  5. Morishita E, Saito M, Kumabashiri I, Asakura H, Matsuda T, Yamaguchi K: Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His). Blood. 1992 Nov 1;80(9):2275-80. [PubMed Link Image]
  6. Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, Roitsch C, Fenton JW 2nd: The structure of a complex of recombinant hirudin and human alpha-thrombin. Science. 1990 Jul 20;249(4966):277-80. [PubMed Link Image]
  7. Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J: The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 1989 Nov;8(11):3467-75. [PubMed Link Image]
  8. Walz DA, Hewett-Emmett D, Seegers WH: Amino acid sequence of human prothrombin fragments 1 and 2. Proc Natl Acad Sci U S A. 1977 May;74(5):1969-72. [PubMed Link Image]
  9. Henriksen RA, Mann KG: Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity. Biochemistry. 1989 Mar 7;28(5):2078-82. [PubMed Link Image]
  10. Degen SJ, Davie EW: Nucleotide sequence of the gene for human prothrombin. Biochemistry. 1987 Sep 22;26(19):6165-77. [PubMed Link Image]
  11. 3242619 Henriksen RA, Mann KG: Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382. Biochemistry. 1988 Dec 27;27(26):9160-5.
  12. 3567158 Miyata T, Morita T, Inomoto T, Kawauchi S, Shirakami A, Iwanaga S: Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima. Biochemistry. 1987 Feb 24;26(4):1117-22.
  13. 3759958 Rabiet MJ, Blashill A, Furie B, Furie BC: Prothrombin fragment 1 X 2 X 3, a major product of prothrombin activation in human plasma. J Biol Chem. 1986 Oct 5;261(28):13210-5.
  14. 3771562 Rabiet MJ, Furie BC, Furie B: Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273. J Biol Chem. 1986 Nov 15;261(32):15045-8.
  15. 3801671 Inomoto T, Shirakami A, Kawauchi S, Shigekiyo T, Saito S, Miyoshi K, Morita T, Iwanaga S: Prothrombin Tokushima: characterization of dysfunctional thrombin derived from a variant of human prothrombin. Blood. 1987 Feb;69(2):565-9.
  16. 6305407 Degen SJ, MacGillivray RT, Davie EW: Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin. Biochemistry. 1983 Apr 26;22(9):2087-97.
  17. 6405779 Board PG, Shaw DC: Determination of the amino acid substitution in human prothrombin type 3 (157 Glu leads to Lys) and the localization of a third thrombin cleavage site. Br J Haematol. 1983 Jun;54(2):245-54.
  18. 7792730 Degen SJ, McDowell SA, Sparks LM, Scharrer I: Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala. Thromb Haemost. 1995 Feb;73(2):203-9.
  19. 7865694 James HL, Kim DJ, Zheng DQ, Girolami A: Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site. Blood Coagul Fibrinolysis. 1994 Oct;5(5):841-4.
  20. 8071320 Rydel TJ, Yin M, Padmanabhan KP, Blankenship DT, Cardin AD, Correa PE, Fenton JW 2nd, Tulinsky A: Crystallographic structure of human gamma-thrombin. J Biol Chem. 1994 Sep 2;269(35):22000-6.
  21. 873923 Butkowski RJ, Elion J, Downing MR, Mann KG: Primary structure of human prethrombin 2 and alpha-thrombin. J Biol Chem. 1977 Jul 25;252(14):4942-57.
  22. 9214615 van de Locht A, Bode W, Huber R, Le Bonniec BF, Stone SR, Esmon CT, Stubbs MT: The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin. EMBO J. 1997 Jun 2;16(11):2977-84.
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 787
Target 2 Name Vitamin K epoxide reductase complex subunit 1
Target 2 Synonyms
  1. EC 1.1.4.1
  2. Vitamin K1 2,3-epoxide reductase subunit 1
Target 2 Gene Name VKORC1
Target 2 Protein Sequence >Vitamin K epoxide reductase complex subunit 1 
MGSTWGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWG
RGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSVYL
AWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH
Target 2 Number of Residues 165
Target 2 Molecular Weight 18235
Target 2 Theoretical pI 9.58
Target 2 GO Classification Not Available
Target 2 General Function Involved in vitamin-K-epoxide reductase (warfarin-sensitive) activity
Target 2 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
Target 2 Pathways
Name SMPDB Link KEGG Link
Biosynthesis of steroids map00100 Link Image
Target 2 Reactions
  • 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
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 9-29
  • 101-123
  • 127-149
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 40217983 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q9BQB6 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name VKOR1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >492 bp 
ATGGGCAGCACCTGGGGGAGCCCTGGCTGGGTGCGGCTCGCTCTTTGCCTGACGGGCTTA
GTGCTCTCGCTCTACGCGCTGCACGTGAAGGCGGCGCGCGCCCGGGACCGGGATTACCGC
GCGCTCTGCGACGTGGGCACCGCCATCAGCTGTTCGCGCGTCTTCTCCTCCAGGTGGGGC
AGGGGTTTCGGGCTGGTGGAGCATGTGCTGGGACAGGACAGCATCCTCAATCAATCCAAC
AGCATATTCGGTTGCATCTTCTACACACTACAGCTATTGTTAGGTTGCCTGCGGACACGC
TGGGCCTCTGTCCTGATGCTGCTGAGCTCCCTGGTGTCTCTCGCTGGTTCTGTCTACCTG
GCCTGGATCCTGTTCTTCGTGCTCTATGATTTCTGCATTGTTTGTATCACCACCTATGCT
ATCAACGTGAGCCTGATGTGGCTCAGTTTCCGGAAGGTCCAAGAACCCCAGGGCAAGGCT
AAGAGGCACTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID VKORC1 Link Image
Target 2 GenAtlas ID VKORC1 Link Image
Target 2 HGNC ID HGNC:23663 Link Image
Target 2 Chromosome Location 16
Target 2 Locus 16p11.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed Link Image]
Target 2 Drug References
  1. Fukuda T, Tanabe T, Ohno M, Tougou K, Fujio Y, Azuma J, Yamamoto I, Takeda A: Warfarin dose requirement for patients with both VKORC1 3673A/A and CYP2C9*3/*3 genotypes. Clin Pharmacol Ther. 2006 Nov;80(5):553-4. [PubMed Link Image]
  2. Yin T, Miyata T: Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives. Thromb Res. 2007;120(1):1-10. Epub 2006 Dec 11. [PubMed Link Image]
  3. Osman A, Enstrom C, Lindahl TL: Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype. Blood Coagul Fibrinolysis. 2007 Apr;18(3):293-6. [PubMed Link Image]
  4. Zhu Y, Shennan M, Reynolds KK, Johnson NA, Herrnberger MR, Valdes R Jr, Linder MW: Estimation of warfarin maintenance dose based on VKORC1 (-1639 G>A) and CYP2C9 genotypes. Clin Chem. 2007 Jul;53(7):1199-205. Epub 2007 May 17. [PubMed Link Image]
  5. Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, Baird MF, Acton RT: Influence of CYP2C9 and VKORC1 1173C/T Genotype on the Risk of Hemorrhagic Complications in African-American and European-American Patients on Warfarin. Clin Pharmacol Ther. 2007 Jul 25;. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 4081
Target 3 Name Vitamin K epoxide reductase complex subunit 1-like protein 1
Target 3 Synonyms
  1. VKORC1- like protein 1
Target 3 Gene Name VKORC1L1
Target 3 Protein Sequence >Vitamin K epoxide reductase complex subunit 1-like protein 1 
MAAPVLLRVSVPRWERVARYAVCAAGILLSIYAYHVEREKERDPEHRALCDLGPWVKCSA
ALASRWGRGFGLLGSIFGKDGVLNQPNSVFGLIFYILQLLLGMTASAVAALILMTSSIMS
VVGSLYLAYILYFVLKEFCIICIVTYVLNFLLLIINYKRLVYLNEAWKRQLQPKQD
Target 3 Number of Residues 178
Target 3 Molecular Weight 19836
Target 3 Theoretical pI 9.35
Target 3 GO Classification Not Available
Target 3 General Function Not Available
Target 3 Specific Function Not Available
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 17-37
  • 92-112
  • 114-134
  • 135-155
Target 3 Essentiality Non Essential
Target 3 GenBank ID Protein 40217985 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q8N0U8 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name VKORL_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
Target 3 Gene Sequence >531 bp 
ATGGCGGCTCCCGTCCTGCTAAGAGTGTCGGTGCCGCGGTGGGAGCGGGTGGCCCGGTAT
GCAGTGTGCGCTGCCGGAATCCTGCTCTCCATCTACGCCTACCACGTGGAGCGGGAGAAG
GAGCGGGACCCCGAGCACCGGGCCCTCTGCGACCTGGGGCCCTGGGTGAAGTGCTCCGCC
GCCCTTGCCTCCAGATGGGGTCGAGGATTTGGTCTTTTGGGTTCCATTTTTGGAAAGGAT
GGTGTATTAAACCAGCCAAACAGTGTCTTTGGACTTATATTTTATATACTACAGTTATTA
CTTGGCATGACAGCAAGCGCTGTGGCGGCTTTGATCCTCATGACGTCCTCCATCATGTCG
GTCGTGGGGTCCCTGTACCTGGCCTACATTCTGTACTTTGTGCTGAAGGAGTTCTGCATC
ATCTGCATCGTCACGTACGTGCTGAACTTCCTTCTTCTCATTATCAACTACAAACGACTA
GTTTACTTGAACGAGGCCTGGAAGCGGCAGCTGCAACCCAAGCAGGACTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID VKORC1L1 Link Image
Target 3 GenAtlas ID VKORC1L1 Link Image
Target 3 HGNC ID HGNC:21492 Link Image
Target 3 Chromosome Location 7
Target 3 Locus 7q11.21
Target 3 SNPs SNPJam Report Link Image
Target 3 General References Not Available
Target 3 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.