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
    (R)-limonene 6-monooxygenase activity
heme binding
(S)-limonene 6-monooxygenase activity
monooxygenase activity
(S)-limonene 7-monooxygenase activity
oxygen binding
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
enzyme binding
arachidonic acid epoxygenase activity
oxidoreductase activity
steroid hydroxylase activity
iron ion binding
Processes
    steroid metabolic process
xenobiotic metabolic process
arachidonic acid metabolic process
drug metabolic process
epoxygenase P450 pathway
exogenous drug catabolic process
heterocycle metabolic process
monoterpenoid metabolic process
small molecule metabolic process
omega-hydroxylase P450 pathway
oxidation-reduction 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.
Transmembrane Regions
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 IDNone
GenAtlas ID
HGNC IDHGNC:2621
Chromosome Location10
Locus10q24.1-q24.3
References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]

Related FRC

FRCD ID Name Exact Mass Structure




F05434



Profenofos


373.626




F05445



Thiram


240.416




F05447



Triadimenol


295.767




F05451



Triticonazole


317.817




F05493



Ethinyl Estradiol


296.41




F05511



Pentadecane


212.421




F05513



Simvastatin


418.574




F05557



Hexylresorcinol


194.274




F05558



2(3H)-Benzothiazolethione


334.488




F05561



1-Hexadecanol


242.447




F03288



Benzidine


184.242




F05032



Bifenazate


300.358




F05078



Flusilazole


315.399




F05121



Phosalone


367.799




F05123



Prochloraz


376.662




F05446



Triadimefon


293.751




F06003



Triflumizole


345.75




F05503



N-Decane


142.286




F05507



Isoniazid


137.142




F05571



Ethoxyquin


217.312




F03283



Chlordane


409.758




F03315



Methoxychlor


345.644




F03312



Diazinon


304.35




F03343



Ethion


384.5




F03378



Guthion


317.318




F03381



Chlordecone


490.609




F03387



Parathion


291.258




F03386



Dicofol


370.475




F03440



Phorate


260.4




F03442



Dimethoate


229.3




F02629



Mercuric chloride


271.492




F03757



Chlorbenzylate


325.185




F03774



Bisphenol A


228.291




F03879



Ethanol


46.07




F03892



Rotenone


394.423




F03900



Alachlor


269.769




F03901



Acetochlor


269.769




F03996



Fenoxycarb


301.342




F04032



Thiobencarb


257.776




F04040



Allethrin


302.414




F04043



Resmethrin


338.447




F04044



Tetramethrin


331.412




F04047



Cyfluthrin


434.288




F04050



Cypermethrin


416.298




F04084



Butachlor


311.85




F04086



Metolachlor


283.796




F04158



Hydroxytriphenylstannane


367.035




F04380



Fenpropathrin


349.43




F04743



Clotrimazole


344.842




F04749



Anidulafungin


1140.254




F04783



Sertraline


306.2




F04846



Fenthion


278.321




F05024



Acibenzolar-S-Methyl


210.269




F05026



Ametryn


227.33




F05680



Amitraz


293.414




F05028



Azamethiphos


324.672




F05031



Bensulide


397.503




F05051



Cyprodinil


225.295




F11967



Cyhalofop-butyl


357.381




F05058



Difenoconazole


406.263




F05095



Malathion


330.35




F05065



Fenamidone


311.403




F05064



Etoxazole


359.417




F05066



Fenamiphos


303.36




F05067



Fenhexamid


302.195




F05068



Fenitrothion


277.24




F05072



Flufenacet


363.331




F05089



Indoxacarb


527.837




F05091



Iprodione


330.165




F05081



Fosthiazate


283.341




F05085



Enilconazole


297.179




F05092



Isoxaben


332.4




F05094



Lactofen


461.774




F05112



Napropamide


271.36




F05103



Methidathion


302.318




F05104



Methoxyfenozide


368.477




F05111



Myclobutanil


288.779




F05114



Norflurazon


303.669




F05125



Propargite


350.473




F05127



Propiconazole


342.22




F05130



Pyraclostrobin


387.82




F05143



Tetraconazole


372.145




F05146



Thiazopyr


396.376




F06000



Tralkoxydim


329.44




F05151



Triclosan


289.536




F05154



Vinclozolin


286.108




F05179



Butylparaben


194.23




F05296



Androstenedione


286.4




F05298



Progesterone


314.469




F05319



17-Hydroxyprogesterone


330.468




F06104



Acetamiprid


222.676




F11483



Clodinafop-propargyl


349.742




F05400



Coumaphos


362.761




F05401



Cyazofamid


324.783




F05403



Cyproconazole


291.779




F05405



Diazoxon


288.284




F05413



Ethofumesate


286.342




F05416



Fenarimol


331.196




F05417



Fenbuconazole


336.823




F05422



Hexaconazole


314.21




F05425



Isazofos


313.737




F05427



Maneb


265.284




F05429



Oryzalin


346.358