CP2CJ_HUMAN
ID CP2CJ_HUMAN Reviewed; 490 AA.
AC P33261; P33259; Q8WZB1; Q8WZB2; Q9UCD4;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Cytochrome P450 2C19;
DE EC=1.14.14.1 {ECO:0000269|PubMed:18577768};
DE AltName: Full=(R)-limonene 6-monooxygenase;
DE EC=1.14.14.53 {ECO:0000269|PubMed:11950794};
DE AltName: Full=(S)-limonene 6-monooxygenase;
DE EC=1.14.14.51 {ECO:0000269|PubMed:11950794};
DE AltName: Full=(S)-limonene 7-monooxygenase;
DE EC=1.14.14.52 {ECO:0000269|PubMed:11950794};
DE AltName: Full=CYPIIC17;
DE AltName: Full=CYPIIC19;
DE AltName: Full=Cytochrome P450-11A;
DE AltName: Full=Cytochrome P450-254C;
DE AltName: Full=Fenbendazole monooxygenase (4'-hydroxylating) {ECO:0000305};
DE EC=1.14.14.75 {ECO:0000269|PubMed:23959307};
DE AltName: Full=Mephenytoin 4-hydroxylase;
GN Name=CYP2C19;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CYP2C19*1A), AND VARIANT VAL-331.
RC TISSUE=Liver;
RX PubMed=2009263; DOI=10.1021/bi00227a012;
RA Romkes M., Faletto M.B., Blaisdell J.A., Raucy J.L., Goldstein J.A.;
RT "Cloning and expression of complementary DNAs for multiple members of the
RT human cytochrome P450IIC subfamily.";
RL Biochemistry 30:3247-3255(1991).
RN [2]
RP ERRATUM OF PUBMED:2009263, AND SEQUENCE REVISION.
RX PubMed=8095407; DOI=10.1021/bi00056a025;
RA Romkes M., Faletto M.B., Blaisdell J.A., Raucy J.L., Goldstein J.A.;
RL Biochemistry 32:1390-1390(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-19; ASP-92; ALA-122;
RP HIS-144; VAL-331 AND CYS-410.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-160 AND 274-490.
RA de Morais S.M.F., Blaisdell J.A.;
RT "Gene structure, upstream region and allelic variants of cyp2c19, the s-
RT mephenytoin hydroxylase.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 1-16.
RC TISSUE=Liver;
RX PubMed=8215410; DOI=10.1006/abbi.1993.1506;
RA Wrighton S.A., Stevens J.C., Becker G.W., VandenBranden M.;
RT "Isolation and characterization of human liver cytochrome P450 2C19:
RT correlation between 2C19 and S-mephenytoin 4'-hydroxylation.";
RL Arch. Biochem. Biophys. 306:240-245(1993).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=11950794; DOI=10.1124/dmd.30.5.602;
RA Miyazawa M., Shindo M., Shimada T.;
RT "Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl
RT alcohols by CYP2C9 and CYP2C19 in human liver microsomes.";
RL Drug Metab. Dispos. 30:602-607(2002).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=18577768; DOI=10.1194/jlr.m800199-jlr200;
RA Fer M., Corcos L., Dreano Y., Plee-Gautier E., Salaun J.P., Berthou F.,
RA Amet Y.;
RT "Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in
RT humans: CYP4F3B is the prominent player in PUFA metabolism.";
RL J. Lipid Res. 49:2379-2389(2008).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19965576; DOI=10.1194/jlr.m003061;
RA Lucas D., Goulitquer S., Marienhagen J., Fer M., Dreano Y., Schwaneberg U.,
RA Amet Y., Corcos L.;
RT "Stereoselective epoxidation of the last double bond of polyunsaturated
RT fatty acids by human cytochromes P450.";
RL J. Lipid Res. 51:1125-1133(2010).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=20972997; DOI=10.1002/rcm.4760;
RA Mesaros C., Lee S.H., Blair I.A.;
RT "Analysis of epoxyeicosatrienoic acids by chiral liquid
RT chromatography/electron capture atmospheric pressure chemical ionization
RT mass spectrometry using [13C]-analog internal standards.";
RL Rapid Commun. Mass Spectrom. 24:3237-3247(2010).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23959307; DOI=10.1128/aac.00843-13;
RA Wu Z., Lee D., Joo J., Shin J.H., Kang W., Oh S., Lee D.Y., Lee S.J.,
RA Yea S.S., Lee H.S., Lee T., Liu K.H.;
RT "CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of
RT albendazole and fenbendazole in human liver microsomes and recombinant P450
RT assay systems.";
RL Antimicrob. Agents Chemother. 57:5448-5456(2013).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP POLYMORPHISM.
RX PubMed=28378927; DOI=10.1002/cpt.690;
RA Zhou Y., Ingelman-Sundberg M., Lauschke V.M.;
RT "Worldwide Distribution of Cytochrome P450 Alleles: A Meta-analysis of
RT Population-scale Sequencing Projects.";
RL Clin. Pharmacol. Ther. 102:688-700(2017).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) OF 23-489 IN COMPLEX WITH HEME AND
RP SYNTHETIC INHIBITOR, AND COFACTOR.
RX PubMed=23118231; DOI=10.1074/jbc.m112.424895;
RA Reynald R.L., Sansen S., Stout C.D., Johnson E.F.;
RT "Structural characterization of human cytochrome P450 2C19: active site
RT differences between P450s 2C8, 2C9, and 2C19.";
RL J. Biol. Chem. 287:44581-44591(2012).
RN [15]
RP INVOLVEMENT IN POOR DRUG METABOLISM, AND IDENTIFICATION OF ALLELE
RP CYP2C19*2A.
RX PubMed=8195181; DOI=10.1016/s0021-9258(17)40694-6;
RA de Morais S.M.F., Wilkinson G.R., Blaisdell J., Nakamura K., Meyer U.A.,
RA Goldstein J.A.;
RT "The major genetic defect responsible for the polymorphism of S-mephenytoin
RT metabolism in humans.";
RL J. Biol. Chem. 269:15419-15422(1994).
RN [16]
RP INVOLVEMENT IN POOR DRUG METABOLISM, AND IDENTIFICATION OF ALLELE
RP CYP2C19*3A.
RX PubMed=7969038;
RA De Morais S.M.F., Wilkinson G.R., Blaisdell J., Meyer U.A., Nakamura K.,
RA Goldstein J.A.;
RT "Identification of a new genetic defect responsible for the polymorphism of
RT (S)-mephenytoin metabolism in Japanese.";
RL Mol. Pharmacol. 46:594-598(1994).
RN [17]
RP VARIANT TRP-433.
RX PubMed=9103550;
RA Xiao Z.S., Goldstein J.A., Xie H.G., Blaisdell J., Wang W., Jiang C.H.,
RA Yan F.X., He N., Huang S.L., Xu Z.H., Zhou H.H.;
RT "Differences in the incidence of the CYP2C19 polymorphism affecting the S-
RT mephenytoin phenotype in Chinese Han and Bai populations and identification
RT of a new rare CYP2C19 mutant allele.";
RL J. Pharmacol. Exp. Ther. 281:604-609(1997).
RN [18]
RP VARIANTS ASP-92 AND GLN-132.
RX PubMed=9732415;
RA Ibeanu G.C., Goldstein J.A., Meyer U.A., Benhamou S., Bouchardy C.,
RA Dayer P., Ghanayem B.I., Blaisdell J.;
RT "Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in
RT a Caucasian poor metabolizer of mephenytoin.";
RL J. Pharmacol. Exp. Ther. 286:1490-1495(1998).
RN [19]
RP VARIANT TRP-433.
RX PubMed=10022751; DOI=10.1097/00008571-199804000-00006;
RA Ibeanu G.C., Blaisdell J., Ghanayem B.I., Beyeler C., Benhamou S.,
RA Bouchardy C., Wilkinson G.R., Dayer P., Daly A.K., Goldstein J.A.;
RT "An additional defective allele, CYP2C19*5, contributes to the S-
RT mephenytoin poor metabolizer phenotype in Caucasians.";
RL Pharmacogenetics 8:129-135(1998).
RN [20]
RP VARIANT ARG-120.
RX PubMed=10411572;
RA Ibeanu G.C., Blaisdell J., Ferguson R.J., Ghanayem B.I., Brosen K.,
RA Benhamou S., Bouchardy C., Wilkinson G.R., Dayer P., Goldstein J.A.;
RT "A novel transversion in the intron 5 donor splice junction of CYP2C19 and
RT a sequence polymorphism in exon 3 contribute to the poor metabolizer
RT phenotype for the anticonvulsant drug S-mephenytoin.";
RL J. Pharmacol. Exp. Ther. 290:635-640(1999).
RN [21]
RP VARIANTS PRO-17; LEU-19; HIS-144; HIS-150; LEU-227 AND CYS-410.
RX PubMed=12464799; DOI=10.1097/00008571-200212000-00004;
RA Blaisdell J., Mohrenweiser H., Jackson J., Ferguson S., Coulter S.,
RA Chanas B., Xi T., Ghanayem B., Goldstein J.A.;
RT "Identification and functional characterization of new potentially
RT defective alleles of human CYP2C19.";
RL Pharmacogenetics 12:703-711(2002).
RN [22]
RP VARIANT CYS-442.
RX PubMed=15499191; DOI=10.2133/dmpk.19.236;
RA Morita J., Kobayashi K., Wanibuchi A., Kimura M., Irie S., Ishizaki T.,
RA Chiba K.;
RT "A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a
RT Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation.";
RL Drug Metab. Pharmacokinet. 19:236-238(2004).
RN [23]
RP VARIANTS THR-74; HIS-144 AND LEU-168.
RX PubMed=15469410; DOI=10.1517/14622416.5.7.895;
RA Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q.,
RA McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
RT "Genetic variation in eleven phase I drug metabolism genes in an ethnically
RT diverse population.";
RL Pharmacogenomics 5:895-931(2004).
RN [24]
RP VARIANTS GLY-51; PRO-161 AND HIS-329.
RX PubMed=16141610; DOI=10.2133/dmpk.20.300;
RA Fukushima-Uesaka H., Saito Y., Maekawa K., Ozawa S., Hasegawa R., Kajio H.,
RA Kuzuya N., Yasuda K., Kawamoto M., Kamatani N., Suzuki K., Yanagawa T.,
RA Tohkin M., Sawada J.;
RT "Genetic variations and haplotypes of CYP2C19 in a Japanese population.";
RL Drug Metab. Pharmacokinet. 20:300-307(2005).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576,
CC PubMed:20972997). Mechanistically, uses molecular oxygen inserting one
CC oxygen atom into a substrate, and reducing the second into a water
CC molecule, with two electrons provided by NADPH via cytochrome P450
CC reductase (NADPH--hemoprotein reductase) (PubMed:18577768,
CC PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of
CC carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1
CC position (PubMed:18577768). Catalyzes the epoxidation of double bonds
CC of PUFA (PubMed:20972997, PubMed:19965576). Also metabolizes plant
CC monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to
CC produce carveol and perillyl alcohol (PubMed:11950794). Responsible for
CC the metabolism of a number of therapeutic agents such as the
CC anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain
CC barbiturates, diazepam, propranolol, citalopram and imipramine.
CC Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
CC {ECO:0000269|PubMed:11950794, ECO:0000269|PubMed:18577768,
CC ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20972997,
CC ECO:0000269|PubMed:23959307}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:50076,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:78043, ChEBI:CHEBI:132024;
CC Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50077;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76627; Evidence={ECO:0000269|PubMed:10411572,
CC ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39787, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76636; Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39788;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = 21-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50088, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:132025; Evidence={ECO:0000269|PubMed:18577768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50089;
CC Evidence={ECO:0000305|PubMed:18577768};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131975; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131970; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131969; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131965; Evidence={ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861;
CC Evidence={ECO:0000305|PubMed:19965576, ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76634; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-
CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:136410; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)-
CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:52124, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:136411; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52125;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4R)-limonene + O2 + reduced [NADPH--hemoprotein reductase] =
CC (1R,5S)-carveol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:18957, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15382, ChEBI:CHEBI:15388, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.53;
CC Evidence={ECO:0000269|PubMed:11950794};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4S)-limonene + O2 + reduced [NADPH--hemoprotein reductase] =
CC (1S,5R)-carveol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17945, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15383, ChEBI:CHEBI:15389, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.51;
CC Evidence={ECO:0000269|PubMed:11950794};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4S)-limonene + O2 + reduced [NADPH--hemoprotein reductase] =
CC (4S)-perillyl alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:23432, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:10782, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15383, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.52;
CC Evidence={ECO:0000269|PubMed:11950794};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fenbendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC 4'-hydroxyfenbendazole + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:56292, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77092,
CC ChEBI:CHEBI:140184; EC=1.14.14.75;
CC Evidence={ECO:0000269|PubMed:23959307};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:23118231};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:18577768, ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed:20972997}.
CC -!- PATHWAY: Terpene metabolism; (4R)-limonene degradation.
CC {ECO:0000269|PubMed:11950794}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- INDUCTION: P450 can be induced to high levels in liver and other
CC tissues by various foreign compounds, including drugs, pesticides, and
CC carcinogens.
CC -!- POLYMORPHISM: Genetic variation in CYP2C19 is responsible for poor drug
CC metabolism [MIM:609535]. Individuals can be characterized as either
CC extensive metabolizers (EM) or poor metabolizers (PM). The PM phenotype
CC is inherited in an autosomal recessive manner, with the EM phenotype
CC comprising both homozygous dominant and heterozygote genotypes. There
CC are marked interracial differences in the frequency of this
CC polymorphism. Poor metabolizers represent 2-5% of Caucasians, 13-23% of
CC Asian populations, and as many as 38-79% of individuals of some of the
CC islands of Polynesia and Micronesia. At least 38 different alleles are
CC known including CYP2C19*1A, CYP2C19*1B, CYP2C19*1C, CYP2C19*2A
CC (CYP2C19m1 or CYP2C19m1A), CYP2C19*2B (CYP2C19m1B), CYP2C19*2C
CC (CYP2C19*21), CYP2C19*3A (CYP2C19m2), CYP2C19*3B (CYP2C19*20),
CC CYP2C19*4 (CYP2C19m3), CYP2C19*5A (CYP2C19m4), CYP2C19*5B, CYP2C19*6,
CC CYP2C19*7, CYP2C19*8, CYP2C19*9, CYP2C19*10, CYP2C19*11 CYP2C19*12,
CC CYP2C19*13, CYP2C19*14 CYP2C19*15, CYP2C19*16, CYP2C19*18 and
CC CYP2C19*19. Defective CYP2C19*2 and CYP2C19*3 alleles are characterized
CC by a splice mutation and a stop codon, respectively, and account for
CC most of the PM alleles. The sequence shown is that of allele
CC CYP2C19*1A. {ECO:0000269|PubMed:28378927}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- CAUTION: P450-254C was originally listed as a separate gene (CYP2C17).
CC Resequencing demonstrated that it is not a separate gene, but a
CC chimera. The 5'-portion corresponds to a partial 2C18 clone, and the
CC 3'-portion corresponds to a partial 2C19 clone. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP2C19 alleles;
CC URL="https://www.pharmvar.org/gene/CYP2C19";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cyp2c19/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M61854; AAB59426.1; -; mRNA.
DR EMBL; M61858; AAA52145.1; ALT_SEQ; mRNA.
DR EMBL; L07093; AAA36660.1; ALT_SEQ; mRNA.
DR EMBL; AY796203; AAV41877.1; -; Genomic_DNA.
DR EMBL; AL583836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133513; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L39098; AAL31347.1; -; Genomic_DNA.
DR EMBL; L39097; AAL31347.1; JOINED; Genomic_DNA.
DR EMBL; L39102; AAL31348.1; -; Genomic_DNA.
DR EMBL; L39099; AAL31348.1; JOINED; Genomic_DNA.
DR EMBL; L39100; AAL31348.1; JOINED; Genomic_DNA.
DR EMBL; L39101; AAL31348.1; JOINED; Genomic_DNA.
DR EMBL; L31506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L31507; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L32982; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L32983; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS7436.1; -.
DR PIR; F38462; F38462.
DR PIR; G38462; G38462.
DR PIR; I52418; I52418.
DR RefSeq; NP_000760.1; NM_000769.2.
DR PDB; 4GQS; X-ray; 2.87 A; A/B/C/D=23-489.
DR PDBsum; 4GQS; -.
DR AlphaFoldDB; P33261; -.
DR BioGRID; 107935; 4.
DR IntAct; P33261; 1.
DR STRING; 9606.ENSP00000360372; -.
DR BindingDB; P33261; -.
DR ChEMBL; CHEMBL3622; -.
DR DrugBank; DB08496; (R)-warfarin.
DR DrugBank; DB14055; (S)-Warfarin.
DR DrugBank; DB05812; Abiraterone.
DR DrugBank; DB01418; Acenocoumarol.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB00546; Adinazolam.
DR DrugBank; DB00518; Albendazole.
DR DrugBank; DB00918; Almotriptan.
DR DrugBank; DB12015; Alpelisib.
DR DrugBank; DB06403; Ambrisentan.
DR DrugBank; DB00357; Aminoglutethimide.
DR DrugBank; DB01424; Aminophenazone.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00701; Amprenavir.
DR DrugBank; DB01435; Antipyrine.
DR DrugBank; DB11901; Apalutamide.
DR DrugBank; DB06605; Apixaban.
DR DrugBank; DB00673; Aprepitant.
DR DrugBank; DB01274; Arformoterol.
DR DrugBank; DB06413; Armodafinil.
DR DrugBank; DB06697; Artemether.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB12597; Asciminib.
DR DrugBank; DB11586; Asunaprevir.
DR DrugBank; DB00289; Atomoxetine.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB06442; Avasimibe.
DR DrugBank; DB06626; Axitinib.
DR DrugBank; DB00972; Azelastine.
DR DrugBank; DB01483; Barbital.
DR DrugBank; DB16703; Belumosudil.
DR DrugBank; DB15463; Belzutifan.
DR DrugBank; DB12319; Benzbromarone.
DR DrugBank; DB01086; Benzocaine.
DR DrugBank; DB00443; Betamethasone.
DR DrugBank; DB01128; Bicalutamide.
DR DrugBank; DB11967; Binimetinib.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB00188; Bortezomib.
DR DrugBank; DB12151; Brincidofovir.
DR DrugBank; DB05541; Brivaracetam.
DR DrugBank; DB01558; Bromazepam.
DR DrugBank; DB01222; Budesonide.
DR DrugBank; DB00297; Bupivacaine.
DR DrugBank; DB00921; Buprenorphine.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB08502; Capravirine.
DR DrugBank; DB00564; Carbamazepine.
DR DrugBank; DB00395; Carisoprodol.
DR DrugBank; DB14984; Casimersen.
DR DrugBank; DB06119; Cenobamate.
DR DrugBank; DB00446; Chloramphenicol.
DR DrugBank; DB00672; Chlorpropamide.
DR DrugBank; DB01166; Cilostazol.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB00604; Cisapride.
DR DrugBank; DB00215; Citalopram.
DR DrugBank; DB12499; Clascoterone.
DR DrugBank; DB04920; Clevidipine.
DR DrugBank; DB14025; Clinafloxacin.
DR DrugBank; DB00349; Clobazam.
DR DrugBank; DB06470; Clomethiazole.
DR DrugBank; DB01242; Clomipramine.
DR DrugBank; DB00758; Clopidogrel.
DR DrugBank; DB01559; Clotiazepam.
DR DrugBank; DB00363; Clozapine.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB00531; Cyclophosphamide.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB08912; Dabrafenib.
DR DrugBank; DB00250; Dapsone.
DR DrugBank; DB00705; Delavirdine.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB05351; Dexlansoprazole.
DR DrugBank; DB13762; Dexrabeprazole.
DR DrugBank; DB00514; Dextromethorphan.
DR DrugBank; DB00829; Diazepam.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB00343; Diltiazem.
DR DrugBank; DB01093; Dimethyl sulfoxide.
DR DrugBank; DB01075; Diphenhydramine.
DR DrugBank; DB09167; Dosulepin.
DR DrugBank; DB05928; Dovitinib.
DR DrugBank; DB00590; Doxazosin.
DR DrugBank; DB01142; Doxepin.
DR DrugBank; DB00476; Duloxetine.
DR DrugBank; DB00625; Efavirenz.
DR DrugBank; DB00216; Eletriptan.
DR DrugBank; DB15444; Elexacaftor.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB11718; Encorafenib.
DR DrugBank; DB00109; Enfuvirtide.
DR DrugBank; DB08899; Enzalutamide.
DR DrugBank; DB01175; Escitalopram.
DR DrugBank; DB11823; Esketamine.
DR DrugBank; DB14575; Eslicarbazepine.
DR DrugBank; DB09119; Eslicarbazepine acetate.
DR DrugBank; DB00736; Esomeprazole.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR DrugBank; DB00330; Ethambutol.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB00977; Ethinylestradiol.
DR DrugBank; DB09166; Etizolam.
DR DrugBank; DB01628; Etoricoxib.
DR DrugBank; DB06414; Etravirine.
DR DrugBank; DB12500; Fedratinib.
DR DrugBank; DB00949; Felbamate.
DR DrugBank; DB00574; Fenfluramine.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB12265; Fexinidazole.
DR DrugBank; DB00196; Fluconazole.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00472; Fluoxetine.
DR DrugBank; DB01095; Fluvastatin.
DR DrugBank; DB00176; Fluvoxamine.
DR DrugBank; DB00983; Formoterol.
DR DrugBank; DB01320; Fosphenytoin.
DR DrugBank; DB00317; Gefitinib.
DR DrugBank; DB01241; Gemfibrozil.
DR DrugBank; DB06730; Gestodene.
DR DrugBank; DB01120; Gliclazide.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB00986; Glycopyrronium.
DR DrugBank; DB01018; Guanfacine.
DR DrugBank; DB00502; Haloperidol.
DR DrugBank; DB01355; Hexobarbital.
DR DrugBank; DB00956; Hydrocodone.
DR DrugBank; DB00741; Hydrocortisone.
DR DrugBank; DB06789; Hydroxyprogesterone caproate.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB09054; Idelalisib.
DR DrugBank; DB01181; Ifosfamide.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB00951; Isoniazid.
DR DrugBank; DB09570; Ixazomib.
DR DrugBank; DB06738; Ketobemidone.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB00598; Labetalol.
DR DrugBank; DB06218; Lacosamide.
DR DrugBank; DB00448; Lansoprazole.
DR DrugBank; DB01259; Lapatinib.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB01006; Letrozole.
DR DrugBank; DB08918; Levomilnacipran.
DR DrugBank; DB09198; Lobeglitazone.
DR DrugBank; DB04948; Lofexidine.
DR DrugBank; DB06448; Lonafarnib.
DR DrugBank; DB16220; Lonapegsomatropin.
DR DrugBank; DB01601; Lopinavir.
DR DrugBank; DB00455; Loratadine.
DR DrugBank; DB04871; Lorcaserin.
DR DrugBank; DB12130; Lorlatinib.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB00227; Lovastatin.
DR DrugBank; DB08933; Luliconazole.
DR DrugBank; DB09280; Lumacaftor.
DR DrugBank; DB01283; Lumiracoxib.
DR DrugBank; DB12474; Lynestrenol.
DR DrugBank; DB08932; Macitentan.
DR DrugBank; DB09238; Manidipine.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB01065; Melatonin.
DR DrugBank; DB01043; Memantine.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB00454; Meperidine.
DR DrugBank; DB00532; Mephenytoin.
DR DrugBank; DB00333; Methadone.
DR DrugBank; DB00763; Methimazole.
DR DrugBank; DB05246; Methsuximide.
DR DrugBank; DB09241; Methylene blue.
DR DrugBank; DB00849; Methylphenobarbital.
DR DrugBank; DB00959; Methylprednisolone.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB06595; Midostaurin.
DR DrugBank; DB01171; Moclobemide.
DR DrugBank; DB00745; Modafinil.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB09049; Naloxegol.
DR DrugBank; DB01183; Naloxone.
DR DrugBank; DB04861; Nebivolol.
DR DrugBank; DB00220; Nelfinavir.
DR DrugBank; DB00622; Nicardipine.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB00665; Nilutamide.
DR DrugBank; DB06712; Nilvadipine.
DR DrugBank; DB00717; Norethisterone.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB14881; Oliceridine.
DR DrugBank; DB00338; Omeprazole.
DR DrugBank; DB11632; Opicapone.
DR DrugBank; DB04911; Oritavancin.
DR DrugBank; DB11837; Osilodrostat.
DR DrugBank; DB04938; Ospemifene.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB00239; Oxiconazole.
DR DrugBank; DB00935; Oxymetazoline.
DR DrugBank; DB00213; Pantoprazole.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB00738; Pentamidine.
DR DrugBank; DB00312; Pentobarbital.
DR DrugBank; DB00850; Perphenazine.
DR DrugBank; DB03783; Phenacetin.
DR DrugBank; DB00780; Phenelzine.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB13941; Piperaquine.
DR DrugBank; DB01621; Pipotiazine.
DR DrugBank; DB04951; Pirfenidone.
DR DrugBank; DB06209; Prasugrel.
DR DrugBank; DB01058; Praziquantel.
DR DrugBank; DB14631; Prednisolone phosphate.
DR DrugBank; DB00635; Prednisone.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB01131; Proguanil.
DR DrugBank; DB00420; Promazine.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB00571; Propranolol.
DR DrugBank; DB01589; Quazepam.
DR DrugBank; DB04216; Quercetin.
DR DrugBank; DB01224; Quetiapine.
DR DrugBank; DB00468; Quinine.
DR DrugBank; DB01129; Rabeprazole.
DR DrugBank; DB00980; Ramelteon.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB00615; Rifabutin.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB11753; Rifamycin.
DR DrugBank; DB01201; Rifapentine.
DR DrugBank; DB01220; Rifaximin.
DR DrugBank; DB08864; Rilpivirine.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB06176; Romidepsin.
DR DrugBank; DB05271; Rotigotine.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB11614; Rupatadine.
DR DrugBank; DB06654; Safinamide.
DR DrugBank; DB12543; Samidorphan.
DR DrugBank; DB00418; Secobarbital.
DR DrugBank; DB01037; Selegiline.
DR DrugBank; DB11689; Selumetinib.
DR DrugBank; DB06731; Seproxetine.
DR DrugBank; DB06739; Seratrodast.
DR DrugBank; DB01104; Sertraline.
DR DrugBank; DB00203; Sildenafil.
DR DrugBank; DB00641; Simvastatin.
DR DrugBank; DB06268; Sitaxentan.
DR DrugBank; DB15093; Somapacitan.
DR DrugBank; DB00052; Somatotropin.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB01323; St. John's Wort.
DR DrugBank; DB09118; Stiripentol.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB06204; Tapentadol.
DR DrugBank; DB00966; Telmisartan.
DR DrugBank; DB00444; Teniposide.
DR DrugBank; DB00857; Terbinafine.
DR DrugBank; DB00624; Testosterone.
DR DrugBank; DB13943; Testosterone cypionate.
DR DrugBank; DB13944; Testosterone enanthate.
DR DrugBank; DB13946; Testosterone undecanoate.
DR DrugBank; DB01041; Thalidomide.
DR DrugBank; DB00599; Thiopental.
DR DrugBank; DB00679; Thioridazine.
DR DrugBank; DB00208; Ticlopidine.
DR DrugBank; DB00373; Timolol.
DR DrugBank; DB01007; Tioconazole.
DR DrugBank; DB00932; Tipranavir.
DR DrugBank; DB06137; Tirbanibulin.
DR DrugBank; DB08895; Tofacitinib.
DR DrugBank; DB01124; Tolbutamide.
DR DrugBank; DB01036; Tolterodine.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB01685; Topiroxostat.
DR DrugBank; DB05109; Trabectedin.
DR DrugBank; DB00752; Tranylcypromine.
DR DrugBank; DB12245; Triclabendazole.
DR DrugBank; DB00347; Trimethadione.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB15328; Ubrogepant.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB16349; Vicagrel.
DR DrugBank; DB06684; Vilazodone.
DR DrugBank; DB08828; Vismodegib.
DR DrugBank; DB00582; Voriconazole.
DR DrugBank; DB09068; Vortioxetine.
DR DrugBank; DB14975; Voxelotor.
DR DrugBank; DB00682; Warfarin.
DR DrugBank; DB00549; Zafirlukast.
DR DrugBank; DB00425; Zolpidem.
DR DrugBank; DB00909; Zonisamide.
DR DrugBank; DB09120; Zucapsaicin.
DR DrugCentral; P33261; -.
DR GuidetoPHARMACOLOGY; 1328; -.
DR SwissLipids; SLP:000001589; -.
DR iPTMnet; P33261; -.
DR PhosphoSitePlus; P33261; -.
DR BioMuta; CYP2C19; -.
DR DMDM; 60416369; -.
DR jPOST; P33261; -.
DR MassIVE; P33261; -.
DR PaxDb; P33261; -.
DR PeptideAtlas; P33261; -.
DR PRIDE; P33261; -.
DR ProteomicsDB; 54907; -.
DR Antibodypedia; 3077; 238 antibodies from 31 providers.
DR DNASU; 1557; -.
DR Ensembl; ENST00000371321.9; ENSP00000360372.3; ENSG00000165841.11.
DR GeneID; 1557; -.
DR KEGG; hsa:1557; -.
DR MANE-Select; ENST00000371321.9; ENSP00000360372.3; NM_000769.4; NP_000760.1.
DR UCSC; uc010qnz.3; human.
DR CTD; 1557; -.
DR DisGeNET; 1557; -.
DR GeneCards; CYP2C19; -.
DR HGNC; HGNC:2621; CYP2C19.
DR HPA; ENSG00000165841; Tissue enriched (liver).
DR MalaCards; CYP2C19; -.
DR MIM; 124020; gene.
DR MIM; 609535; phenotype.
DR neXtProt; NX_P33261; -.
DR OpenTargets; ENSG00000165841; -.
DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia.
DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia.
DR Orphanet; 240935; Prediction of resistance to clopidogrel.
DR Orphanet; 413667; Prediction of toxicity or dose selection of antidepressants or antipsychotics.
DR Orphanet; 240921; Prediction of voriconazole toxicity.
DR PharmGKB; PA124; -.
DR VEuPathDB; HostDB:ENSG00000165841; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000163209; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P33261; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P33261; -.
DR TreeFam; TF352043; -.
DR BioCyc; MetaCyc:HS09293-MON; -.
DR BRENDA; 1.14.14.75; 2681.
DR PathwayCommons; P33261; -.
DR Reactome; R-HSA-211981; Xenobiotics.
DR Reactome; R-HSA-211999; CYP2E1 reactions.
DR Reactome; R-HSA-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
DR Reactome; R-HSA-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR SABIO-RK; P33261; -.
DR SignaLink; P33261; -.
DR UniPathway; UPA00199; -.
DR UniPathway; UPA00987; -.
DR BioGRID-ORCS; 1557; 4 hits in 998 CRISPR screens.
DR GeneWiki; CYP2C19; -.
DR GenomeRNAi; 1557; -.
DR Pharos; P33261; Tchem.
DR PRO; PR:P33261; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P33261; protein.
DR Bgee; ENSG00000165841; Expressed in liver and 35 other tissues.
DR ExpressionAtlas; P33261; baseline and differential.
DR Genevisible; P33261; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0052741; F:(R)-limonene 6-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0018675; F:(S)-limonene 6-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0018676; F:(S)-limonene 7-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0120319; F:long-chain fatty acid omega-1 hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0004497; F:monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL.
DR GO; GO:0016712; F: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; IBA:GO_Central.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0008395; F:steroid hydroxylase activity; IMP:BHF-UCL.
DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
DR GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL.
DR GO; GO:0001676; P:long-chain fatty acid metabolic process; IDA:UniProtKB.
DR GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL.
DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; TAS:Reactome.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL.
DR GO; GO:0042178; P:xenobiotic catabolic process; IDA:BHF-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:BHF-UCL.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum;
KW Fatty acid metabolism; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..490
FT /note="Cytochrome P450 2C19"
FT /id="PRO_0000051708"
FT BINDING 435
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:23118231,
FT ECO:0007744|PDB:4GQS"
FT VARIANT 17
FT /note="L -> P (in allele CYP2C19*14; dbSNP:rs55752064)"
FT /evidence="ECO:0000269|PubMed:12464799"
FT /id="VAR_021268"
FT VARIANT 19
FT /note="I -> L (in allele CYP2C19*15; dbSNP:rs17882687)"
FT /evidence="ECO:0000269|PubMed:12464799, ECO:0000269|Ref.3"
FT /id="VAR_021269"
FT VARIANT 51
FT /note="S -> G (in allele CYP2C19*19; dbSNP:rs1564657013)"
FT /evidence="ECO:0000269|PubMed:16141610"
FT /id="VAR_024083"
FT VARIANT 74
FT /note="M -> T (in dbSNP:rs28399505)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024718"
FT VARIANT 92
FT /note="E -> D (in dbSNP:rs17878459)"
FT /evidence="ECO:0000269|PubMed:9732415, ECO:0000269|Ref.3"
FT /id="VAR_021270"
FT VARIANT 120
FT /note="W -> R (in allele CYP2C19*8; loss of activity;
FT dbSNP:rs41291556)"
FT /evidence="ECO:0000269|PubMed:10411572"
FT /id="VAR_008357"
FT VARIANT 122
FT /note="E -> A (in dbSNP:rs17885179)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021271"
FT VARIANT 132
FT /note="R -> Q (in allele CYP2C19*6; loss of activity;
FT dbSNP:rs72552267)"
FT /evidence="ECO:0000269|PubMed:9732415"
FT /id="VAR_008358"
FT VARIANT 144
FT /note="R -> H (in allele CYP2C19*9; dbSNP:rs17884712)"
FT /evidence="ECO:0000269|PubMed:12464799,
FT ECO:0000269|PubMed:15469410, ECO:0000269|Ref.3"
FT /id="VAR_021272"
FT VARIANT 150
FT /note="R -> H (in allele CYP2C19*11; dbSNP:rs58973490)"
FT /evidence="ECO:0000269|PubMed:12464799"
FT /id="VAR_021273"
FT VARIANT 161
FT /note="A -> P (in dbSNP:rs181297724)"
FT /evidence="ECO:0000269|PubMed:16141610"
FT /id="VAR_024084"
FT VARIANT 168
FT /note="F -> L (in dbSNP:rs28399510)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024719"
FT VARIANT 227
FT /note="P -> L (in allele CYP2C19*10; dbSNP:rs6413438)"
FT /evidence="ECO:0000269|PubMed:12464799"
FT /id="VAR_020123"
FT VARIANT 329
FT /note="R -> H (in allele CYP2C19*18; dbSNP:rs138142612)"
FT /evidence="ECO:0000269|PubMed:16141610"
FT /id="VAR_024085"
FT VARIANT 331
FT /note="I -> V (in allele CYP2C19*1B, allele CYP2C19*1C,
FT allele CYP2C19*2A, allele CYP2C19*2B, allele CYP2C19*2C,
FT allele CYP2C19*2E, allele CYP2C19*2F, allele CYP2C19*2G,
FT allele CYP2C19*2H, allele CYP2C19*2J, allele CYP2C19*3A,
FT allele CYP2C19*3B, allele CYP2C19*3C, allele CYP2C19*4A,
FT allele CYP2C19*4B, allele CYP2C19*6, allele CYP2C19*9,
FT allele CYP2C19*10, allele CYP2C19*11, allele CYP2C19*12,
FT allele CYP2C19*13, allele CYP2C19*14, allele CYP2C19*15,
FT allele CYP2C19*18, allele CYP2C19*19, allele CYP2C19*22,
FT allele CYP2C19*23, allele CYP2C19*24, allele CYP2C19*25,
FT allele CYP2C19*26, allele CYP2C19*27, allele CYP2C19*28,
FT allele CYP2C19*29, allele CYP2C19*31, allele CYP2C19*32,
FT allele CYP2C19*33 and allele CYP2C19*35; dbSNP:rs3758581)"
FT /evidence="ECO:0000269|PubMed:15469410,
FT ECO:0000269|PubMed:16141610, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.5"
FT /id="VAR_001255"
FT VARIANT 410
FT /note="R -> C (in allele CYP2C19*13; dbSNP:rs17879685)"
FT /evidence="ECO:0000269|PubMed:12464799, ECO:0000269|Ref.3"
FT /id="VAR_021274"
FT VARIANT 433
FT /note="R -> W (in allele CYP2C19*5A and allele CYP2C19*5B;
FT loss of activity; dbSNP:rs56337013)"
FT /evidence="ECO:0000269|PubMed:10022751,
FT ECO:0000269|PubMed:9103550"
FT /id="VAR_008359"
FT VARIANT 442
FT /note="R -> C (in allele CYP2C19*16; lowered catalytic
FT activity; dbSNP:rs192154563)"
FT /evidence="ECO:0000269|PubMed:15499191"
FT /id="VAR_021275"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 50..61
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 80..87
FT /evidence="ECO:0007829|PDB:4GQS"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:4GQS"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 117..130
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 135..139
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 141..158
FT /evidence="ECO:0007829|PDB:4GQS"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:4GQS"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 169..182
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 192..209
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 211..218
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 228..254
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 263..273
FT /evidence="ECO:0007829|PDB:4GQS"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 284..297
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 300..315
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 317..330
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 339..344
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 346..359
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 391..395
FT /evidence="ECO:0007829|PDB:4GQS"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 409..412
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:4GQS"
FT HELIX 438..455
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 456..462
FT /evidence="ECO:0007829|PDB:4GQS"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:4GQS"
FT STRAND 485..489
FT /evidence="ECO:0007829|PDB:4GQS"
SQ SEQUENCE 490 AA; 55945 MW; B451BFFE9A009465 CRC64;
MDPFVVLVLC LSCLLLLSIW RQSSGRGKLP PGPTPLPVIG NILQIDIKDV SKSLTNLSKI
YGPVFTLYFG LERMVVLHGY EVVKEALIDL GEEFSGRGHF PLAERANRGF GIVFSNGKRW
KEIRRFSLMT LRNFGMGKRS IEDRVQEEAR CLVEELRKTK ASPCDPTFIL GCAPCNVICS
IIFQKRFDYK DQQFLNLMEK LNENIRIVST PWIQICNNFP TIIDYFPGTH NKLLKNLAFM
ESDILEKVKE HQESMDINNP RDFIDCFLIK MEKEKQNQQS EFTIENLVIT AADLLGAGTE
TTSTTLRYAL LLLLKHPEVT AKVQEEIERV IGRNRSPCMQ DRGHMPYTDA VVHEVQRYID
LIPTSLPHAV TCDVKFRNYL IPKGTTILTS LTSVLHDNKE FPNPEMFDPR HFLDEGGNFK
KSNYFMPFSA GKRICVGEGL ARMELFLFLT FILQNFNLKS LIDPKDLDTT PVVNGFASVP
PFYQLCFIPV
