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 24-JAN-2024, entry version 209. 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 CC [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--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 CC [NADPH--hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--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 SMR; 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; DB14973; Abrocitinib. 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; DB14737; Cannabinol. DR DrugBank; DB08502; Capravirine. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB06016; Cariprazine. 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; DB00470; Dronabinol. 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; DB05087; Ganaxolone. 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; DB14921; Mavacamten. 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; DB16236; Mitapivat. 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; DB16267; Olutasidenib. 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; DB11697; Pacritinib. DR DrugBank; DB05467; Palovarotene. 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; DB02709; Resveratrol. 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; DB12834; Secnidazole. 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; DB06083; Tapinarof. DR DrugBank; DB12020; Tecovirimat. DR DrugBank; DB00966; Telmisartan. DR DrugBank; DB12095; Telotristat ethyl. 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; DB00285; Venlafaxine. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB16349; Vicagrel. DR DrugBank; DB06684; Vilazodone. DR DrugBank; DB08828; Vismodegib. DR DrugBank; DB11739; Vonoprazan. 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; 9606-ENSP00000360372; -. DR PeptideAtlas; P33261; -. DR ProteomicsDB; 54907; -. DR Antibodypedia; 3077; 276 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 AGR; HGNC:2621; -. 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 PharmGKB; PA124; -. DR VEuPathDB; HostDB:ENSG00000165841; -. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000163209; -. DR HOGENOM; CLU_001570_22_3_1; -. DR InParanoid; P33261; -. DR OMA; TPWIQIC; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; P33261; -. DR TreeFam; TF352043; -. DR BioCyc; MetaCyc:HS09293-MONOMER; -. 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 1082 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 cell types or tissues. DR ExpressionAtlas; P33261; baseline and differential. 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: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 CDD; cd20665; CYP2C-like; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24300:SF360; CYTOCHROME P450 2C19; 1. DR PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P33261; HS. 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 //