Cytochrome P450 2C19

NameCytochrome P450 2C19
Synonyms
  • (R)-limonene 6-monooxygenase
  • (S)-limonene 6-monooxygenase
  • (S)-limonene 7-monooxygenase
  • 1.14.13.-
  • CYPIIC17
  • CYPIIC19
  • Cytochrome P450-11A
  • Cytochrome P450-254C
  • Mephenytoin 4-hydroxylase
Gene NameCYP2C19
OrganismHuman
Amino acid sequence
>lcl|BSEQ0020694|Cytochrome P450 2C19
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI
YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM
ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID
LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK
KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP
PFYQLCFIPV
Number of residues490
Molecular Weight55930.545
Theoretical pI7.42
GO Classification
Functions
  • heme binding
  • monooxygenase activity
  • oxygen binding
  • arachidonic acid epoxygenase activity
  • steroid hydroxylase activity
  • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
  • (R)-limonene 6-monooxygenase activity
  • enzyme binding
  • (S)-limonene 6-monooxygenase activity
  • (S)-limonene 7-monooxygenase activity
  • oxidoreductase activity
  • iron ion binding
Processes
  • heterocycle metabolic process
  • monoterpenoid metabolic process
  • omega-hydroxylase P450 pathway
  • small molecule metabolic process
  • oxidation-reduction process
  • steroid metabolic process
  • xenobiotic metabolic process
  • arachidonic acid metabolic process
  • drug metabolic process
  • epoxygenase P450 pathway
  • exogenous drug catabolic process
Components
  • cytoplasm
  • endoplasmic reticulum membrane
  • intracellular membrane-bounded organelle
General FunctionSteroid hydroxylase activity
Specific FunctionResponsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID181344
UniProtKB IDP33261
UniProtKB Entry NameCP2CJ_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0020695|Cytochrome P450 2C19 (CYP2C19)
ATGGATCCTTTTGTGGTCCTTGTGCTCTGTCTCTCATGTTTGCTTCTCCTTTCAATCTGG
AGACAGAGCTCTGGGAGAGGAAAACTCCCTCCTGGCCCCACTCCTCTCCCAGTGATTGGA
AATATCCTACAGATAGATATTAAGGATGTCAGCAAATCCTTAACCAATCTCTCAAAAATC
TATGGCCCTGTGTTCACTCTGTATTTTGGCCTGGAACGCATGGTGGTGCTGCATGGATAT
GAAGTGGTGAAGGAAGCCCTGATTGATCTTGGAGAGGAGTTTTCTGGAAGAGGCCATTTC
CCACTGGCTGAAAGAGCTAACAGAGGATTTGGAATCGTTTTCAGCAATGGAAAGAGATGG
AAGGAGATCCGGCGTTTCTCCCTCATGACGCTGCGGAATTTTGGGATGGGGAAGAGGAGC
ATTGAGGACCGTGTTCAAGAGGAAGCCCGCTGCCTTGTGGAGGAGTTGAGAAAAACCAAG
GCTTCACCCTGTGATCCCACTTTCATCCTGGGCTGTGCTCCCTGCAATGTGATCTGCTCC
ATTATTTTCCAGAAACGTTTCGATTATAAAGATCAGCAATTTCTTAACTTGATGGAAAAA
TTGAATGAAAACATCAGGATTGTAAGCACCCCCTGGATCCAGATATGCAATAATTTTCCC
ACTATCATTGATTATTTCCCGGGAACCCATAACAAATTACTTAAAAACCTTGCTTTTATG
GAAAGTGATATTTTGGAGAAAGTAAAAGAACACCAAGAATCGATGGACATCAACAACCCT
CGGGACTTTATTGATTGCTTCCTGATCAAAATGGAGAAGGAAAAGCAAAACCAACAGTCT
GAATTCACTATTGAAAACTTGGTAATCACTGCAGCTGACTTACTTGGAGCTGGGACAGAG
ACAACAAGCACAACCCTGAGATATGCTCTCCTTCTCCTGCTGAAGCACCCAGAGGTCACA
GCTAAAGTCCAGGAAGAGATTGAACGTGTCATTGGCAGAAACCGGAGCCCCTGCATGCAG
GACAGGGGCCACATGCCCTACACAGATGCTGTGGTGCACGAGGTCCAGAGATACATCGAC
CTCATCCCCACCAGCCTGCCCCATGCAGTGACCTGTGACGTTAAATTCAGAAACTACCTC
ATTCCCAAGGGCACAACCATATTAACTTCCCTCACTTCTGTGCTACATGACAACAAAGAA
TTTCCCAACCCAGAGATGTTTGACCCTCGTCACTTTCTGGATGAAGGTGGAAATTTTAAG
AAAAGTAACTACTTCATGCCTTTCTCAGCAGGAAAACGGATTTGTGTGGGAGAGGGCCTG
GCCCGCATGGAGCTGTTTTTATTCCTGACCTTCATTTTACAGAACTTTAACCTGAAATCT
CTGATTGACCCAAAGGACCTTGACACAACTCCTGTTGTCAATGGATTTGCTTCTGTCCCG
CCCTTCTATCAGCTGTGCTTCATTCCTGTCTGA
GenBank Gene IDM61854
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:2621
Chromosome Location10
Locus10q24.1-q24.3
References
  1. Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA: Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. Biochemistry. 1991 Apr 2;30(13):3247-55. 2009263
  2. Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA: Cloning and expression of complementary DNAs for multiple members of the human cytochrome PH50IIC subfamily. Biochemistry. 1993 Feb 9;32(5):1390. 8095407
  3. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. 15164054
  4. Wrighton SA, Stevens JC, Becker GW, VandenBranden M: Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation. Arch Biochem Biophys. 1993 Oct;306(1):240-5. 8215410
  5. Miyazawa M, Shindo M, Shimada T: Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes. Drug Metab Dispos. 2002 May;30(5):602-7. 11950794
  6. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  7. Reynald RL, Sansen S, Stout CD, Johnson EF: Structural characterization of human cytochrome P450 2C19: active site differences between P450s 2C8, 2C9, and 2C19. J Biol Chem. 2012 Dec 28;287(53):44581-91. doi: 10.1074/jbc.M112.424895. Epub 2012 Nov 1. 23118231
  8. de Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA: The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem. 1994 Jun 3;269(22):15419-22. 8195181
  9. De Morais SM, Wilkinson GR, Blaisdell J, Meyer UA, Nakamura K, Goldstein JA: Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol. 1994 Oct;46(4):594-8. 7969038
  10. Xiao ZS, Goldstein JA, Xie HG, Blaisdell J, Wang W, Jiang CH, Yan FX, He N, Huang SL, Xu ZH, Zhou HH: Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. J Pharmacol Exp Ther. 1997 Apr;281(1):604-9. 9103550
  11. Ibeanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer P, Ghanayem BI, Blaisdell J: Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther. 1998 Sep;286(3):1490-5. 9732415
  12. Ibeanu GC, Blaisdell J, Ghanayem BI, Beyeler C, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Daly AK, Goldstein JA: An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics. 1998 Apr;8(2):129-35. 10022751
  13. Ibeanu GC, Blaisdell J, Ferguson RJ, Ghanayem BI, Brosen K, Benhamou S, Bouchardy C, Wilkinson GR, Dayer P, Goldstein JA: A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin. J Pharmacol Exp Ther. 1999 Aug;290(2):635-40. 10411572
  14. Blaisdell J, Mohrenweiser H, Jackson J, Ferguson S, Coulter S, Chanas B, Xi T, Ghanayem B, Goldstein JA: Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics. 2002 Dec;12(9):703-11. 12464799
  15. Morita J, Kobayashi K, Wanibuchi A, Kimura M, Irie S, Ishizaki T, Chiba K: A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation. Drug Metab Pharmacokinet. 2004 Jun;19(3):236-8. 15499191
  16. Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP: Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004 Oct;5(7):895-931. 15469410
  17. Fukushima-Uesaka H, Saito Y, Maekawa K, Ozawa S, Hasegawa R, Kajio H, Kuzuya N, Yasuda K, Kawamoto M, Kamatani N, Suzuki K, Yanagawa T, Tohkin M, Sawada J: Genetic variations and haplotypes of CYP2C19 in a Japanese population. Drug Metab Pharmacokinet. 2005 Aug;20(4):300-7. 16141610