ID CP2C9_HUMAN Reviewed; 490 AA. AC P11712; P11713; Q16756; Q16872; Q5VX92; Q6IRV8; Q8WW80; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 3. DT 27-MAR-2024, entry version 242. DE RecName: Full=Cytochrome P450 2C9 {ECO:0000303|PubMed:8809086}; DE EC=1.14.14.1 {ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:9435160, ECO:0000269|PubMed:9866708}; 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=CYPIIC9; DE AltName: Full=Cholesterol 25-hydroxylase {ECO:0000303|PubMed:3079764}; DE AltName: Full=Cytochrome P-450MP; DE AltName: Full=Cytochrome P450 MP-4; DE AltName: Full=Cytochrome P450 MP-8; DE AltName: Full=Cytochrome P450 PB-1; DE AltName: Full=S-mephenytoin 4-hydroxylase {ECO:0000303|PubMed:3079764}; GN Name=CYP2C9 {ECO:0000303|PubMed:11950794, ECO:0000312|HGNC:HGNC:2623}; GN Synonyms=CYP2C10 {ECO:0000303|PubMed:8215449}; 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] (ISOFORM 1), AND VARIANT CYS-144. RX PubMed=2827463; RA Meehan R.R., Gosden J.R., Rout D., Hastie N.D., Friedberg T., Adesnik M., RA Buckland R., van Heyningen V., Fletcher J.M., Spurr N.K., Sweeney J., RA Wolf C.R.; RT "Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin RT and steroid oxidations that maps to chromosome 10."; RL Am. J. Hum. Genet. 42:26-37(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT CYS-144. RX PubMed=3697070; DOI=10.1093/nar/15.23.10053; RA Kimura S., Pastewka J., Gelboin H.V., Gonzalez F.J.; RT "cDNA and amino acid sequences of two members of the human P450IIC gene RT subfamily."; RL Nucleic Acids Res. 15:10053-10054(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-144; HIS-150; ARG-251; RP GLY-272; LEU-359 AND SER-489. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Mammary gland; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP CYS-144. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-490 (ISOFORM 1). RC TISSUE=Liver; RX PubMed=2963808; DOI=10.1093/oxfordjournals.jbchem.a122145; RA Yasumori T., Kawano S., Nagata K., Shimada M., Yamazoe Y., Kato R.; RT "Nucleotide sequence of a human liver cytochrome P-450 related to the rat RT male specific form."; RL J. Biochem. 102:1075-1082(1987). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-490 (ISOFORM 1), AND VARIANTS CYS-358 AND RP ASP-417. RC TISSUE=Liver; RX PubMed=3032244; DOI=10.1021/bi00378a016; RA Umbenhauer D.R., Martin M.V., Lloyd R.S., Guengerich F.P.; RT "Cloning and sequence determination of a complementary DNA related to human RT liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase."; RL Biochemistry 26:1094-1099(1987). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-490 (ISOFORM 1), AND VARIANTS CYS-358 AND RP ASP-417. RX PubMed=3196692; DOI=10.1021/bi00418a039; RA Ged C., Umbenhauer D.R., Bellew T.M., Bork R.W., Srivastava P.K., RA Shinriki N., Lloyd R.S., Guengerich F.P.; RT "Characterization of cDNAs, mRNAs, and proteins related to human liver RT microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase."; RL Biochemistry 27:6929-6940(1988). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-490 (ISOFORM 1). RX PubMed=1445376; RA Ohgiya S., Komori M., Ohi H., Shiramatsu K., Shinriki N., Kamataki T.; RT "Six-base deletion occurring in messages of human cytochrome P-450 in the RT CYP2C subfamily results in reduction of tolbutamide hydroxylase activity."; RL Biochem. Int. 27:1073-1081(1992). RN [12] RP PROTEIN SEQUENCE OF 1-29, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, AND CHARACTERIZATION. RX PubMed=3079764; DOI=10.1016/s0021-9258(17)36183-5; RA Shimada T., Misono K.S., Guengerich F.P.; RT "Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a RT prototype of genetic polymorphism in oxidative drug metabolism. RT Purification and characterization of two similar forms involved in the RT reaction."; RL J. Biol. Chem. 261:909-921(1986). RN [13] RP PROTEIN SEQUENCE OF 1-25, AND CATALYTIC ACTIVITY. RX PubMed=3243766; DOI=10.1093/oxfordjournals.jbchem.a122582; RA Komori M., Hashizume T., Ohi H., Miura T., Kitada M., Nagashima K., RA Kamataki T.; RT "Cytochrome P-450 in human liver microsomes: high-performance liquid RT chromatographic isolation of three forms and their characterization."; RL J. Biochem. 104:912-916(1988). RN [14] RP PARTIAL PROTEIN SEQUENCE. RX PubMed=1857342; RA Srivastava P.K., Yun C.H., Beaune P.H., Ged C., Guengerich F.P.; RT "Separation of human liver microsomal tolbutamide hydroxylase and (S)- RT mephenytoin 4'-hydroxylase cytochrome P-450 enzymes."; RL Mol. Pharmacol. 40:69-79(1991). RN [15] RP PROTEIN SEQUENCE OF 1-9; 21-157; 169-249; 264-424; 426-476 AND 484-487. RX PubMed=8809086; DOI=10.1006/abbi.1996.0414; RA Haining R.L., Hunter A.P., Veronese M.E., Trager W.F., Rettie A.E.; RT "Allelic variants of human cytochrome P450 2C9: baculovirus-mediated RT expression, purification, structural characterization, substrate RT stereoselectivity, and prochiral selectivity of the wild-type and I359L RT mutant forms."; RL Arch. Biochem. Biophys. 333:447-458(1996). RN [16] RP PROTEIN SEQUENCE OF 1-20. RX PubMed=8215449; DOI=10.1006/abbi.1993.1536; RA Sandhu P., Baba T., Guengerich F.P.; RT "Expression of modified cytochrome P450 2C10 (2C9) in Escherichia coli, RT purification, and reconstitution of catalytic activity."; RL Arch. Biochem. Biophys. 306:443-450(1993). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RC TISSUE=Kidney; RX PubMed=7574697; DOI=10.1006/abbi.1995.1438; RA Zeldin D.C., DuBois R.N., Falck J.R., Capdevila J.H.; RT "Molecular cloning, expression and characterization of an endogenous human RT cytochrome P450 arachidonic acid epoxygenase isoform."; RL Arch. Biochem. Biophys. 322:76-86(1995). RN [18] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9866708; DOI=10.1006/abio.1998.2897; RA Bylund J., Ericsson J., Oliw E.H.; RT "Analysis of cytochrome P450 metabolites of arachidonic and linoleic acids RT by liquid chromatography-mass spectrometry with ion trap MS."; RL Anal. Biochem. 265:55-68(1998). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=9435160; RA Bylund J., Kunz T., Valmsen K., Oliw E.H.; RT "Cytochromes P450 with bisallylic hydroxylation activity on arachidonic and RT linoleic acids studied with human recombinant enzymes and with human and RT rat liver microsomes."; RL J. Pharmacol. Exp. Ther. 284:51-60(1998). RN [20] 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 [21] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=12865317; DOI=10.1210/en.2003-0192; RA Lee A.J., Cai M.X., Thomas P.E., Conney A.H., Zhu B.T.; RT "Characterization of the oxidative metabolites of 17beta-estradiol and RT estrone formed by 15 selectively expressed human cytochrome p450 RT isoforms."; RL Endocrinology 144:3382-3398(2003). RN [22] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY. RX PubMed=15766564; DOI=10.1016/j.bbrc.2005.02.103; RA Barbosa-Sicard E., Markovic M., Honeck H., Christ B., Muller D.N., RA Schunck W.H.; RT "Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C RT subfamily."; RL Biochem. Biophys. Res. Commun. 329:1275-1281(2005). RN [23] 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 [24] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND PATHWAY. RX PubMed=21576599; DOI=10.1194/jlr.m014084; RA Honda A., Miyazaki T., Ikegami T., Iwamoto J., Maeda T., Hirayama T., RA Saito Y., Teramoto T., Matsuzaki Y.; RT "Cholesterol 25-hydroxylation activity of CYP3A."; RL J. Lipid Res. 52:1509-1516(2011). RN [25] 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 [26] RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 30-490. RX PubMed=12861225; DOI=10.1038/nature01862; RA Williams P.A., Cosme J., Ward A., Angove H.C., Matak-Vinkovic D., Jhoti H.; RT "Crystal structure of human cytochrome P450 2C9 with bound warfarin."; RL Nature 424:464-468(2003). RN [27] RP VARIANTS CYS-144 AND LEU-359. RX PubMed=8946475; DOI=10.1097/00008571-199610000-00007; RA Stubbins M.J., Harries L.W., Smith G., Tarbit M.H., Wolf C.R.; RT "Genetic analysis of the human cytochrome P450 CYP2C9 locus."; RL Pharmacogenetics 6:429-439(1996). RN [28] RP VARIANTS CYS-144; CYS-358; LEU-359 AND ASP-417. RX PubMed=9110362; DOI=10.1097/00008571-199702000-00007; RA Bhasker C.R., Miners J.O., Coulter S., Birkett D.J.; RT "Allelic and functional variability of cytochrome P4502C9."; RL Pharmacogenetics 7:51-58(1997). RN [29] RP VARIANT THR-359. RX PubMed=10739176; DOI=10.1097/00008571-200002000-00011; RA Imai J., Ieiri I., Mamiya K., Miyahara S., Furuumi H., Nanba E., Yamane M., RA Fukumaki Y., Ninomiya H., Tashiro N., Otsubo K., Higuchi S.; RT "Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic RT patients: genetic analysis of the CYP2C9 locus."; RL Pharmacogenetics 10:85-89(2000). RN [30] RP VARIANT GLU-360. RX PubMed=11455026; DOI=10.1124/mol.60.2.382; RA Dickmann L.J., Rettie A.E., Kneller M.B., Kim R.B., Wood A.J., Stein C.M., RA Wilkinson G.R., Schwarz U.I.; RT "Identification and functional characterization of a new CYP2C9 variant RT (CYP2C9*5) expressed among African Americans."; RL Mol. Pharmacol. 60:382-387(2001). RN [31] RP VARIANT TRP-335. RX PubMed=11926893; DOI=10.1001/jama.287.13.1690; RA Higashi M.K., Veenstra D.L., Kondo L.M., Wittkowsky A.K., RA Srinouanprachanh S.L., Farin F.M., Rettie A.E.; RT "Association between CYP2C9 genetic variants and anticoagulation-related RT outcomes during warfarin therapy."; RL JAMA 287:1690-1698(2002). RN [32] RP VARIANTS CYS-144; HIS-150; ARG-251; TRP-335; LEU-359; GLU-360 AND PRO-413. 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 [33] RP VARIANT LEU-125. RX PubMed=21451434; DOI=10.1097/fpc.0b013e328344c340; RA Ciccacci C., Falconi M., Paolillo N., Oteri F., Forte V., Novelli G., RA Desideri A., Borgiani P.; RT "Characterization of a novel CYP2C9 gene mutation and structural RT bioinformatic protein analysis in a warfarin hypersensitive patient."; RL Pharmacogenet. Genomics 21:344-346(2011). RN [34] RP VARIANT HIS-204. RX PubMed=23582453; DOI=10.1016/j.thromres.2013.03.019; RA Nahar R., Dube D., Parakh R., Deb R., Saxena R., Singh T.P., Verma I.C.; RT "Implication of novel CYP2C9*57 (p.Asn204His) variant in coumarin RT hypersensitivity."; RL Thromb. Res. 131:535-539(2013). RN [35] RP VARIANT HIS-125. RX PubMed=24956244; DOI=10.2217/pgs.14.47; RA Lee Y.M., Eggen J., Soni V., Drozda K., Nutescu E.A., Cavallari L.H.; RT "Warfarin dose requirements in a patient with the CYP2C9*14 allele."; RL Pharmacogenomics 15:909-914(2014). RN [36] RP VARIANT PHE-434, CHARACTERIZATION OF VARIANT PHE-434, BIOPHYSICOCHEMICAL RP PROPERTIES, AND FUNCTION. RX PubMed=25994031; DOI=10.1124/dmd.115.063412; RA Dai D.P., Wang S.H., Li C.B., Geng P.W., Cai J., Wang H., Hu G.X., RA Cai J.P.; RT "Identification and Functional Assessment of a New CYP2C9 Allelic Variant RT CYP2C9*59."; RL Drug Metab. Dispos. 43:1246-1249(2015). CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of CC various endogenous substrates, including fatty acids and steroids CC (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, CC PubMed:15766564, PubMed:19965576, PubMed:21576599). Mechanistically, CC uses molecular oxygen inserting one oxygen atom into a substrate, and CC reducing the second into a water molecule, with two electrons provided CC by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) CC (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, CC PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the CC epoxidation of double bonds of polyunsaturated fatty acids (PUFA) CC (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). CC Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes CC cholesterol toward 25-hydroxycholesterol, a physiological regulator of CC cellular cholesterol homeostasis (PubMed:21576599). Exhibits low CC catalytic activity for the formation of catechol estrogens from 17beta- CC estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 CC (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation CC with double-bond migration of polyunsaturated fatty acids (PUFA) CC (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes CC such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol CC and perillyl alcohol (PubMed:11950794). Contributes to the wide CC pharmacokinetics variability of the metabolism of drugs such as S- CC warfarin, diclofenac, phenytoin, tolbutamide and losartan CC (PubMed:25994031). {ECO:0000269|PubMed:11950794, CC ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:15766564, CC ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:21576599, CC ECO:0000269|PubMed:25994031, ECO:0000269|PubMed:7574697, CC ECO:0000269|PubMed:9435160, ECO:0000269|PubMed:9866708}. 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:12865317, ECO:0000269|PubMed:21576599, CC ECO:0000269|PubMed:9435160, ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; CC Evidence={ECO:0000305|PubMed:12865317, ECO:0000305|PubMed:21576599, CC ECO:0000305|PubMed:9435160, ECO:0000305|PubMed:9866708}; 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:7574697}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885; CC Evidence={ECO:0000305|PubMed:7574697}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (8S,9R)-epoxy-(5Z,11Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49928, 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:131974; Evidence={ECO:0000269|PubMed:7574697}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49929; CC Evidence={ECO:0000305|PubMed:7574697}; 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:7574697}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881; CC Evidence={ECO:0000305|PubMed:7574697}; 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:7574697}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877; CC Evidence={ECO:0000305|PubMed:7574697}; 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:7574697}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; CC Evidence={ECO:0000305|PubMed:19965576, ECO:0000305|PubMed:7574697}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49856, 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:131964; Evidence={ECO:0000269|PubMed:19965576, CC ECO:0000269|PubMed:7574697}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; CC Evidence={ECO:0000305|PubMed:19965576, ECO:0000305|PubMed:7574697}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 8,9-epoxy-(5Z,11Z,14Z,17Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52168, 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:136439; Evidence={ECO:0000269|PubMed:15766564}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52169; CC Evidence={ECO:0000305|PubMed:15766564}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z,17Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52172, 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:136441; Evidence={ECO:0000269|PubMed:15766564}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52173; CC Evidence={ECO:0000305|PubMed:15766564}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z,17Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52176, 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:136443; Evidence={ECO:0000269|PubMed:15766564}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52177; CC Evidence={ECO:0000305|PubMed:15766564}; 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:15766564, CC ECO:0000269|PubMed:19965576}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; CC Evidence={ECO:0000305|PubMed:15766564, ECO:0000305|PubMed:19965576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cholesterol + O2 + reduced [NADPH--hemoprotein reductase] = CC 25-hydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:50256, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16113, ChEBI:CHEBI:42977, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:21576599}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50257; CC Evidence={ECO:0000305|PubMed:21576599}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] CC = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, CC ChEBI:CHEBI:28744, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC Evidence={ECO:0000269|PubMed:12865317}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; CC Evidence={ECO:0000305|PubMed:12865317}; CC -!- CATALYTIC ACTIVITY: CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2- CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:12865317}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; CC Evidence={ECO:0000305|PubMed:12865317}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (11R)-hydroxy-(5Z,8Z,12E,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52492, 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:78836; Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52493; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (12R)-hydroxy-(5Z,8Z,10E,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52300, 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:83343; Evidence={ECO:0000269|PubMed:9435160, CC ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52301; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (15R)-hydroxy-(5Z,8Z,11Z,13E)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52496, 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:78837; Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52497; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 10-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52296, 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:133345; Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52297; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoate + O2 + reduced [NADPH--hemoprotein CC reductase] = (13R)-hydroxy-(9Z,11E)-octadecadienoate + H(+) + H2O + CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52500, CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30245, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136655; CC Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52501; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoate + O2 + reduced [NADPH--hemoprotein CC reductase] = (9R)-hydroxy-(10E,12Z)-octadecadienoate + H(+) + H2O + CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52504, CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30245, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77895; CC Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52505; CC Evidence={ECO:0000305|PubMed:9866708}; 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:9435160, CC ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39760; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 13(S)-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52508, 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:136654; Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52509; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:51472, 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:84024; Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51473; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:51480, 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:76625; Evidence={ECO:0000269|PubMed:9866708}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51481; CC Evidence={ECO:0000305|PubMed:9866708}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = 13-hydroxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52292, 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:136524; Evidence={ECO:0000269|PubMed:9435160}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52293; CC Evidence={ECO:0000305|PubMed:9435160}; 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 -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=12.2 uM for (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate (epoxygenation) CC {ECO:0000269|PubMed:15766564}; CC KM=14.3 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (epoxygenation) CC {ECO:0000269|PubMed:15766564}; CC KM=1.25 mM for S-mephenytoin {ECO:0000269|PubMed:3079764}; CC KM=46.24 uM for tolbutamide {ECO:0000269|PubMed:25994031}; CC KM=4.73 uM for diclofenac {ECO:0000269|PubMed:25994031}; CC KM=1.58 uM for losartan {ECO:0000269|PubMed:25994031}; CC Vmax=210.3 pmol/min/pmol enzyme with losartan as substrate CC {ECO:0000269|PubMed:25994031}; CC Vmax=29.1 nmol/min/nmol enzyme toward CC (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate (epoxidation) CC {ECO:0000269|PubMed:15766564}; CC Vmax=29.2 nmol/min/nmol enzyme toward CC (5Z,8Z,11Z,14Z)-eicosatetraenoate (epoxidation) CC {ECO:0000269|PubMed:15766564}; CC Vmax=9.22 pmol/min/pmol enzyme with tolbutamide as substrate CC {ECO:0000269|PubMed:25994031}; CC Vmax=17.16 pmol/min/pmol enzyme with diclofenac as substrate CC {ECO:0000269|PubMed:25994031}; CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism. CC {ECO:0000269|PubMed:15766564, ECO:0000269|PubMed:19965576, CC ECO:0000269|PubMed:7574697, ECO:0000269|PubMed:9435160}. CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism. CC {ECO:0000269|PubMed:21576599}. CC -!- PATHWAY: Terpene metabolism; (4R)-limonene degradation. CC {ECO:0000269|PubMed:11950794}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral CC membrane protein. Microsome membrane {ECO:0000269|PubMed:21576599}; CC Peripheral membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11712-1; Sequence=Displayed; CC Name=2; CC IsoId=P11712-2; Sequence=VSP_055573, VSP_055574; CC -!- INDUCTION: By rifampicin. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium; CC Note=CYP2C9 alleles; CC URL="https://www.pharmvar.org/gene/CYP2C9"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cyp2c9/"; 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; AY341248; AAP88931.1; -; Genomic_DNA. DR EMBL; AY702706; AAT94065.1; -; Genomic_DNA. DR EMBL; AK289420; BAF82109.1; -; mRNA. DR EMBL; AL359672; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW50019.1; -; Genomic_DNA. DR EMBL; CH471066; EAW50020.1; -; Genomic_DNA. DR EMBL; BC020754; AAH20754.1; -; mRNA. DR EMBL; BC070317; AAH70317.1; -; mRNA. DR EMBL; BC125054; AAI25055.1; -; mRNA. DR EMBL; D00173; BAA00123.1; -; mRNA. DR EMBL; M15331; AAA52157.1; -; mRNA. DR EMBL; M21939; AAA52158.1; -; mRNA. DR EMBL; M21940; AAA52159.1; -; mRNA. DR EMBL; S46963; AAB23864.2; ALT_SEQ; mRNA. DR CCDS; CCDS7437.1; -. [P11712-1] DR PIR; B38462; B38462. DR PIR; D28951; D28951. DR RefSeq; NP_000762.2; NM_000771.3. [P11712-1] DR RefSeq; XP_016871247.1; XM_017015758.1. DR PDB; 1OG2; X-ray; 2.60 A; A/B=30-490. DR PDB; 1OG5; X-ray; 2.55 A; A/B=30-490. DR PDB; 1R9O; X-ray; 2.00 A; A=18-490. DR PDB; 4NZ2; X-ray; 2.45 A; A/B=30-490. DR PDB; 5A5I; X-ray; 2.00 A; A=23-489. DR PDB; 5A5J; X-ray; 2.90 A; A=23-489. DR PDB; 5K7K; X-ray; 2.30 A; A=23-489. DR PDB; 5W0C; X-ray; 2.00 A; A=18-489. DR PDB; 5X23; X-ray; 2.00 A; A=19-490. DR PDB; 5X24; X-ray; 2.48 A; A=19-490. DR PDB; 5XXI; X-ray; 2.30 A; A=28-489. DR PDB; 6VLT; X-ray; 3.12 A; A/B/C/D/E/F/G/H=19-490. DR PDB; 7RL2; X-ray; 2.23 A; A=24-490. DR PDBsum; 1OG2; -. DR PDBsum; 1OG5; -. DR PDBsum; 1R9O; -. DR PDBsum; 4NZ2; -. DR PDBsum; 5A5I; -. DR PDBsum; 5A5J; -. DR PDBsum; 5K7K; -. DR PDBsum; 5W0C; -. DR PDBsum; 5X23; -. DR PDBsum; 5X24; -. DR PDBsum; 5XXI; -. DR PDBsum; 6VLT; -. DR PDBsum; 7RL2; -. DR AlphaFoldDB; P11712; -. DR SMR; P11712; -. DR BioGRID; 107937; 104. DR IntAct; P11712; 12. DR STRING; 9606.ENSP00000260682; -. DR BindingDB; P11712; -. DR ChEMBL; CHEMBL3397; -. DR DrugBank; DB08496; (R)-warfarin. DR DrugBank; DB14055; (S)-Warfarin. DR DrugBank; DB12001; Abemaciclib. DR DrugBank; DB05812; Abiraterone. DR DrugBank; DB14973; Abrocitinib. DR DrugBank; DB06736; Aceclofenac. DR DrugBank; DB01418; Acenocoumarol. DR DrugBank; DB00414; Acetohexamide. DR DrugBank; DB14033; Acetyl sulfisoxazole. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB15568; Adagrasib. DR DrugBank; DB06594; Agomelatine. DR DrugBank; DB00969; Alosetron. DR DrugBank; DB12015; Alpelisib. DR DrugBank; DB00404; Alprazolam. DR DrugBank; DB01424; Aminophenazone. DR DrugBank; DB01118; Amiodarone. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00613; Amodiaquine. DR DrugBank; DB00701; Amprenavir. DR DrugBank; DB01217; Anastrozole. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB11901; Apalutamide. DR DrugBank; DB06605; Apixaban. DR DrugBank; DB00673; Aprepitant. DR DrugBank; DB04557; Arachidonic Acid. DR DrugBank; DB01274; Arformoterol. DR DrugBank; DB06413; Armodafinil. DR DrugBank; DB06697; Artemether. DR DrugBank; DB12597; Asciminib. DR DrugBank; DB11586; Asunaprevir. DR DrugBank; DB01072; Atazanavir. DR DrugBank; DB01076; Atorvastatin. DR DrugBank; DB01117; Atovaquone. DR DrugBank; DB15011; Avacopan. DR DrugBank; DB06237; Avanafil. DR DrugBank; DB15233; Avapritinib. DR DrugBank; DB06442; Avasimibe. DR DrugBank; DB11995; Avatrombopag. DR DrugBank; DB00972; Azelastine. DR DrugBank; DB08822; Azilsartan medoxomil. DR DrugBank; DB05015; Belinostat. DR DrugBank; DB12319; Benzbromarone. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB01128; Bicalutamide. DR DrugBank; DB13746; Bioallethrin. DR DrugBank; DB13975; Black cohosh. DR DrugBank; DB00188; Bortezomib. DR DrugBank; DB00559; Bosentan. DR DrugBank; DB12151; Brincidofovir. DR DrugBank; DB05541; Brivaracetam. DR DrugBank; DB01222; Budesonide. DR DrugBank; DB00921; Buprenorphine. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB08875; Cabozantinib. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB13919; Candesartan. DR DrugBank; DB00796; Candesartan cilexetil. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB14737; Cannabinol. DR DrugBank; DB01101; Capecitabine. DR DrugBank; DB08502; Capravirine. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB13406; Carbutamide. DR DrugBank; DB06016; Cariprazine. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB14984; Casimersen. DR DrugBank; DB00482; Celecoxib. DR DrugBank; DB09063; Ceritinib. DR DrugBank; DB00439; Cerivastatin. DR DrugBank; DB00672; Chlorpropamide. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB00568; Cinnarizine. DR DrugBank; DB00604; Cisapride. DR DrugBank; DB00515; Cisplatin. DR DrugBank; DB12499; Clascoterone. DR DrugBank; DB04920; Clevidipine. DR DrugBank; DB14025; Clinafloxacin. DR DrugBank; DB00758; Clopidogrel. DR DrugBank; DB00257; Clotrimazole. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB04665; Coumarin. DR DrugBank; DB05219; Crisaborole. DR DrugBank; DB11672; Curcumin. DR DrugBank; DB14635; Curcumin sulfate. DR DrugBank; DB01176; Cyclizine. DR DrugBank; DB00531; Cyclophosphamide. DR DrugBank; DB08912; Dabrafenib. DR DrugBank; DB11963; Dacomitinib. DR DrugBank; DB06292; Dapagliflozin. DR DrugBank; DB00250; Dapsone. DR DrugBank; DB11943; Delafloxacin. DR DrugBank; DB00705; Delavirdine. DR DrugBank; DB00304; Desogestrel. DR DrugBank; DB09213; Dexibuprofen. DR DrugBank; DB04856; Dexloxiglumide. DR DrugBank; DB00514; Dextromethorphan. DR DrugBank; DB11994; Diacerein. DR DrugBank; DB00829; Diazepam. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB00266; Dicoumarol. DR DrugBank; DB00255; Diethylstilbestrol. DR DrugBank; DB08995; Diosmin. DR DrugBank; DB01075; Diphenhydramine. DR DrugBank; DB03756; Doconexent. DR DrugBank; DB00757; Dolasetron. DR DrugBank; DB00843; Donepezil. DR DrugBank; DB00869; Dorzolamide. DR DrugBank; DB09167; Dosulepin. 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; DB08899; Enzalutamide. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB12147; Erdafitinib. DR DrugBank; DB11823; Esketamine. 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; DB00655; Estrone. DR DrugBank; DB04574; Estrone sulfate. DR DrugBank; DB00330; Ethambutol. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB00977; Ethinylestradiol. DR DrugBank; DB00749; Etodolac. DR DrugBank; DB01628; Etoricoxib. DR DrugBank; DB06414; Etravirine. DR DrugBank; DB04854; Febuxostat. DR DrugBank; DB00949; Felbamate. DR DrugBank; DB01023; Felodipine. DR DrugBank; DB00574; Fenfluramine. DR DrugBank; DB01039; Fenofibrate. DR DrugBank; DB03317; Ferroheme C. DR DrugBank; DB01195; Flecainide. DR DrugBank; DB00322; Floxuridine. DR DrugBank; DB00196; Fluconazole. DR DrugBank; DB13136; Fluindione. DR DrugBank; DB04841; Flunarizine. DR DrugBank; DB01544; Flunitrazepam. DR DrugBank; DB00544; Fluorouracil. DR DrugBank; DB00472; Fluoxetine. DR DrugBank; DB00712; Flurbiprofen. DR DrugBank; DB01095; Fluvastatin. DR DrugBank; DB00176; Fluvoxamine. DR DrugBank; DB00983; Formoterol. DR DrugBank; DB06717; Fosaprepitant. DR DrugBank; DB01320; Fosphenytoin. DR DrugBank; DB15149; Futibatinib. DR DrugBank; DB00317; Gefitinib. DR DrugBank; DB01241; Gemfibrozil. DR DrugBank; DB01645; Genistein. DR DrugBank; DB01381; Ginkgo biloba. DR DrugBank; DB08962; Glibornuride. DR DrugBank; DB01120; Gliclazide. DR DrugBank; DB00222; Glimepiride. DR DrugBank; DB01067; Glipizide. DR DrugBank; DB01251; Gliquidone. DR DrugBank; DB01289; Glisoxepide. DR DrugBank; DB01016; Glyburide. DR DrugBank; DB00986; Glycopyrronium. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB01159; Halothane. DR DrugBank; DB01355; Hexobarbital. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB00327; Hydromorphone. DR DrugBank; DB01050; Ibuprofen. DR DrugBank; DB01177; Idarubicin. DR DrugBank; DB01181; Ifosfamide. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB06370; Indisulam. DR DrugBank; DB00328; Indomethacin. DR DrugBank; DB04818; Iproniazid. DR DrugBank; DB01029; Irbesartan. DR DrugBank; DB11633; Isavuconazole. DR DrugBank; DB00951; Isoniazid. DR DrugBank; DB11757; Istradefylline. DR DrugBank; DB14568; Ivosidenib. DR DrugBank; DB09570; Ixazomib. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB06738; Ketobemidone. DR DrugBank; DB01026; Ketoconazole. DR DrugBank; DB01009; Ketoprofen. DR DrugBank; DB00465; Ketorolac. DR DrugBank; DB06218; Lacosamide. DR DrugBank; DB00448; Lansoprazole. DR DrugBank; DB01097; Leflunomide. DR DrugBank; DB09078; Lenvatinib. DR DrugBank; DB11560; Lesinurad. DR DrugBank; DB12070; Letermovir. DR DrugBank; DB01137; Levofloxacin. DR DrugBank; DB04725; Licofelone. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB11611; Lifitegrast. DR DrugBank; DB17083; Linzagolix. DR DrugBank; DB09198; Lobeglitazone. DR DrugBank; DB06448; Lonafarnib. DR DrugBank; DB01601; Lopinavir. DR DrugBank; DB00455; Loratadine. DR DrugBank; DB06725; Lornoxicam. DR DrugBank; DB00678; Losartan. 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; DB00603; Medroxyprogesterone acetate. DR DrugBank; DB00784; Mefenamic acid. DR DrugBank; DB01065; Melatonin. DR DrugBank; DB00814; Meloxicam. DR DrugBank; DB00170; Menadione. DR DrugBank; DB00532; Mephenytoin. DR DrugBank; DB01357; Mestranol. DR DrugBank; DB13675; Metahexamide. DR DrugBank; DB00333; Methadone. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB09241; Methylene blue. DR DrugBank; DB00959; Methylprednisolone. DR DrugBank; DB00916; Metronidazole. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB06595; Midostaurin. DR DrugBank; DB00834; Mifepristone. DR DrugBank; DB16236; Mitapivat. DR DrugBank; DB01171; Moclobemide. DR DrugBank; DB00745; Modafinil. DR DrugBank; DB00471; Montelukast. DR DrugBank; DB00486; Nabilone. DR DrugBank; DB14011; Nabiximols. DR DrugBank; DB00461; Nabumetone. DR DrugBank; DB00788; Naproxen. DR DrugBank; DB00731; Nateglinide. DR DrugBank; DB00220; Nelfinavir. DR DrugBank; DB09048; Netupitant. DR DrugBank; DB00238; Nevirapine. DR DrugBank; DB00622; Nicardipine. DR DrugBank; DB06803; Niclosamide. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB01115; Nifedipine. DR DrugBank; DB04868; Nilotinib. DR DrugBank; DB00957; Norgestimate. DR DrugBank; DB06174; Noscapine. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB14881; Oliceridine. DR DrugBank; DB09080; Olodaterol. DR DrugBank; DB16267; Olutasidenib. DR DrugBank; DB00338; Omeprazole. DR DrugBank; DB00904; Ondansetron. DR DrugBank; DB11632; Opicapone. DR DrugBank; DB04911; Oritavancin. DR DrugBank; DB04938; Ospemifene. DR DrugBank; DB00621; Oxandrolone. DR DrugBank; DB00617; Paramethadione. DR DrugBank; DB08439; Parecoxib. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB00022; Peginterferon alfa-2b. DR DrugBank; DB00850; Perphenazine. DR DrugBank; DB12978; Pexidartinib. DR DrugBank; DB03783; Phenacetin. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00946; Phenprocoumon. DR DrugBank; DB00812; Phenylbutazone. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB13941; Piperaquine. DR DrugBank; DB04951; Pirfenidone. DR DrugBank; DB00554; Piroxicam. DR DrugBank; DB08860; Pitavastatin. DR DrugBank; DB15822; Pralsetinib. DR DrugBank; DB01411; Pranlukast. DR DrugBank; DB06209; Prasugrel. DR DrugBank; DB14631; Prednisolone phosphate. DR DrugBank; DB00635; Prednisone. DR DrugBank; DB00794; Primidone. DR DrugBank; DB01032; Probenecid. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB01131; Proguanil. DR DrugBank; DB00420; Promazine. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB09288; Propacetamol. DR DrugBank; DB00818; Propofol. DR DrugBank; DB01589; Quazepam. DR DrugBank; DB04216; Quercetin. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB00468; Quinine. DR DrugBank; DB01129; Rabeprazole. DR DrugBank; DB00980; Ramelteon. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB02709; Resveratrol. DR DrugBank; DB13174; Rhein. DR DrugBank; DB00615; Rifabutin. DR DrugBank; DB01045; Rifampicin. DR DrugBank; DB11753; Rifamycin. DR DrugBank; DB01201; Rifapentine. DR DrugBank; DB08864; Rilpivirine. DR DrugBank; DB12457; Rimegepant. DR DrugBank; DB00503; Ritonavir. DR DrugBank; DB00533; Rofecoxib. DR DrugBank; DB00412; Rosiglitazone. DR DrugBank; DB01098; Rosuvastatin. DR DrugBank; DB12332; Rucaparib. DR DrugBank; DB11614; Rupatadine. DR DrugBank; DB08877; Ruxolitinib. DR DrugBank; DB00936; Salicylic acid. 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; DB12371; Siponimod. DR DrugBank; DB06268; Sitaxentan. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB15569; Sotorasib. DR DrugBank; DB09118; Stiripentol. DR DrugBank; DB06820; Sulconazole. DR DrugBank; DB00359; Sulfadiazine. DR DrugBank; DB06150; Sulfadimethoxine. DR DrugBank; DB00576; Sulfamethizole. DR DrugBank; DB01015; Sulfamethoxazole. DR DrugBank; DB08798; Sulfamoxole. DR DrugBank; DB06729; Sulfaphenazole. DR DrugBank; DB00891; Sulfapyridine. DR DrugBank; DB01138; Sulfinpyrazone. DR DrugBank; DB00263; Sulfisoxazole. DR DrugBank; DB00870; Suprofen. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB06204; Tapentadol. DR DrugBank; DB06083; Tapinarof. DR DrugBank; DB12095; Telotristat ethyl. DR DrugBank; DB00231; Temazepam. DR DrugBank; DB00444; Teniposide. DR DrugBank; DB00469; Tenoxicam. DR DrugBank; DB15133; Tepotinib. 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; DB01154; Thiamylal. DR DrugBank; DB08816; Ticagrelor. DR DrugBank; DB00208; Ticlopidine. DR DrugBank; DB04831; Tienilic acid. DR DrugBank; DB06137; Tirbanibulin. DR DrugBank; DB00839; Tolazamide. DR DrugBank; DB01124; Tolbutamide. DR DrugBank; DB00323; Tolcapone. DR DrugBank; DB01036; Tolterodine. DR DrugBank; DB01685; Topiroxostat. DR DrugBank; DB00214; Torasemide. DR DrugBank; DB05109; Trabectedin. DR DrugBank; DB07615; Tranilast. DR DrugBank; DB00752; Tranylcypromine. DR DrugBank; DB00374; Treprostinil. DR DrugBank; DB00755; Tretinoin. DR DrugBank; DB12245; Triclabendazole. DR DrugBank; DB12808; Trifarotene. DR DrugBank; DB00347; Trimethadione. DR DrugBank; DB00440; Trimethoprim. DR DrugBank; DB00726; Trimipramine. DR DrugBank; DB00197; Troglitazone. DR DrugBank; DB15328; Ubrogepant. DR DrugBank; DB14989; Umbralisib. DR DrugBank; DB13609; Umifenovir. DR DrugBank; DB00580; Valdecoxib. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB00177; Valsartan. DR DrugBank; DB08881; Vemurafenib. DR DrugBank; DB00285; Venlafaxine. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB06652; Vicriviroc. DR DrugBank; DB01080; Vigabatrin. 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; DB04898; Ximelagatran. DR DrugBank; DB00549; Zafirlukast. DR DrugBank; DB06737; Zaltoprofen. DR DrugBank; DB00495; Zidovudine. DR DrugBank; DB00744; Zileuton. DR DrugBank; DB00425; Zolpidem. DR DrugBank; DB01198; Zopiclone. DR DrugBank; DB09120; Zucapsaicin. DR DrugCentral; P11712; -. DR GuidetoPHARMACOLOGY; 1326; -. DR SwissLipids; SLP:000001203; -. DR iPTMnet; P11712; -. DR PhosphoSitePlus; P11712; -. DR BioMuta; CYP2C9; -. DR DMDM; 6686268; -. DR EPD; P11712; -. DR jPOST; P11712; -. DR MassIVE; P11712; -. DR PaxDb; 9606-ENSP00000260682; -. DR PeptideAtlas; P11712; -. DR ProteomicsDB; 52801; -. [P11712-1] DR Antibodypedia; 4244; 365 antibodies from 32 providers. DR DNASU; 1559; -. DR Ensembl; ENST00000260682.8; ENSP00000260682.6; ENSG00000138109.11. [P11712-1] DR Ensembl; ENST00000461906.1; ENSP00000495649.1; ENSG00000138109.11. [P11712-2] DR GeneID; 1559; -. DR KEGG; hsa:1559; -. DR MANE-Select; ENST00000260682.8; ENSP00000260682.6; NM_000771.4; NP_000762.2. DR AGR; HGNC:2623; -. DR CTD; 1559; -. DR DisGeNET; 1559; -. DR GeneCards; CYP2C9; -. DR HGNC; HGNC:2623; CYP2C9. DR HPA; ENSG00000138109; Tissue enriched (liver). DR MalaCards; CYP2C9; -. DR MIM; 601130; gene. DR neXtProt; NX_P11712; -. DR OpenTargets; ENSG00000138109; -. DR PharmGKB; PA126; -. DR VEuPathDB; HostDB:ENSG00000138109; -. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000163209; -. DR HOGENOM; CLU_001570_22_3_1; -. DR InParanoid; P11712; -. DR OMA; HANQWAI; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; P11712; -. DR TreeFam; TF352043; -. DR BioCyc; MetaCyc:HS06458-MONOMER; -. DR BRENDA; 1.14.99.38; 2681. DR PathwayCommons; P11712; -. 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-9027307; Biosynthesis of maresin-like SPMs. DR Reactome; R-HSA-9749641; Aspirin ADME. DR SABIO-RK; P11712; -. DR SignaLink; P11712; -. DR SIGNOR; P11712; -. DR UniPathway; UPA00296; -. DR UniPathway; UPA00383; -. DR UniPathway; UPA00987; -. DR BioGRID-ORCS; 1559; 15 hits in 1110 CRISPR screens. DR ChiTaRS; CYP2C9; human. DR EvolutionaryTrace; P11712; -. DR GeneWiki; CYP2C9; -. DR GenomeRNAi; 1559; -. DR Pharos; P11712; Tchem. DR PRO; PR:P11712; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P11712; Protein. DR Bgee; ENSG00000138109; Expressed in right lobe of liver and 119 other cell types or tissues. DR ExpressionAtlas; P11712; 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:0008405; F:arachidonic acid 11,12-epoxygenase activity; IEA:RHEA. DR GO; GO:0008404; F:arachidonic acid 14,15-epoxygenase activity; IEA:RHEA. DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IDA:UniProtKB. DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC. DR GO; GO:0034875; F:caffeine oxidase activity; IDA:BHF-UCL. DR GO; GO:0020037; F:heme binding; IBA:GO_Central. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB. 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:0008395; F:steroid hydroxylase activity; IMP:BHF-UCL. DR GO; GO:0043603; P:amide metabolic process; IDA:BHF-UCL. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0019373; P:epoxygenase P450 pathway; IDA:UniProtKB. DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB. DR GO; GO:0046456; P:icosanoid biosynthetic process; IDA:UniProtKB. DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome. DR GO; GO:0032787; P:monocarboxylic acid metabolic process; IDA:BHF-UCL. 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:0070989; P:oxidative demethylation; IDA:BHF-UCL. DR GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL. DR GO; GO:0019627; P:urea metabolic process; IDA: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:SF336; CYTOCHROME P450 2C9; 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; P11712; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane; KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase; KW Reference proteome; Steroid metabolism; Sterol metabolism. FT CHAIN 1..490 FT /note="Cytochrome P450 2C9" FT /id="PRO_0000051700" 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 VAR_SEQ 161..162 FT /note="AS -> GG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055573" FT VAR_SEQ 163..490 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055574" FT VARIANT 19 FT /note="L -> I (in allele CYP2C9*7; dbSNP:rs67807361)" FT /id="VAR_018862" FT VARIANT 125 FT /note="R -> H (in allele CYP2C9*35; dbSNP:rs72558189)" FT /evidence="ECO:0000269|PubMed:24956244" FT /id="VAR_075286" FT VARIANT 125 FT /note="R -> L (in allele CYP2C9*14; dbSNP:rs72558189)" FT /evidence="ECO:0000269|PubMed:21451434" FT /id="VAR_075287" FT VARIANT 144 FT /note="R -> C (in allele CYP2C9*2; dbSNP:rs1799853)" FT /evidence="ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2827463, FT ECO:0000269|PubMed:3697070, ECO:0000269|PubMed:8946475, FT ECO:0000269|PubMed:9110362, ECO:0000269|Ref.3" FT /id="VAR_008343" FT VARIANT 150 FT /note="R -> H (in allele CYP2C9*8; dbSNP:rs7900194)" FT /evidence="ECO:0000269|PubMed:15469410, ECO:0000269|Ref.3" FT /id="VAR_018863" FT VARIANT 204 FT /note="N -> H (in allele CYP2C9*57)" FT /evidence="ECO:0000269|PubMed:23582453" FT /id="VAR_075288" FT VARIANT 251 FT /note="H -> R (in allele CYP2C9*9; dbSNP:rs2256871)" FT /evidence="ECO:0000269|PubMed:15469410, ECO:0000269|Ref.3" FT /id="VAR_018864" FT VARIANT 272 FT /note="E -> G (in allele CYP2C9*10; dbSNP:rs9332130)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018865" FT VARIANT 335 FT /note="R -> W (in allele CYP2C9*11; dbSNP:rs28371685)" FT /evidence="ECO:0000269|PubMed:11926893, FT ECO:0000269|PubMed:15469410" FT /id="VAR_018866" FT VARIANT 358 FT /note="Y -> C (in dbSNP:rs1057909)" FT /evidence="ECO:0000269|PubMed:3032244, FT ECO:0000269|PubMed:3196692, ECO:0000269|PubMed:9110362" FT /id="VAR_008344" FT VARIANT 359 FT /note="I -> L (in allele CYP2C9*3; responsible for the FT tolbutamide poor metabolizer phenotype; dbSNP:rs1057910)" FT /evidence="ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:8946475, ECO:0000269|PubMed:9110362, FT ECO:0000269|Ref.3" FT /id="VAR_008345" FT VARIANT 359 FT /note="I -> T (in allele CYP2C9*4; dbSNP:rs56165452)" FT /evidence="ECO:0000269|PubMed:10739176" FT /id="VAR_013515" FT VARIANT 360 FT /note="D -> E (in allele CYP2C9*5; increases the K(m) value FT for substrates tested; dbSNP:rs28371686)" FT /evidence="ECO:0000269|PubMed:11455026, FT ECO:0000269|PubMed:15469410" FT /id="VAR_013516" FT VARIANT 413 FT /note="L -> P (in dbSNP:rs28371687)" FT /evidence="ECO:0000269|PubMed:15469410" FT /id="VAR_024717" FT VARIANT 417 FT /note="G -> D" FT /evidence="ECO:0000269|PubMed:3032244, FT ECO:0000269|PubMed:3196692, ECO:0000269|PubMed:9110362" FT /id="VAR_008346" FT VARIANT 434 FT /note="I -> F (in allele CYP2C9*59; produces warfarin FT hypersensitivity; increases affinity but highly decreases FT enzymatic activity for tolbutamide; no effect on affinity FT but decreases enzymatic activity for diclofenac; decreases FT affinity and highly decreases enzymatic activity for FT losartan)" FT /evidence="ECO:0000269|PubMed:25994031" FT /id="VAR_075289" FT VARIANT 489 FT /note="P -> S (in allele CYP2C9*12; dbSNP:rs9332239)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018867" FT CONFLICT 4 FT /note="L -> I (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 6 FT /note="V -> S (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 14 FT /note="L -> M (in Ref. 11; AAB23864)" FT /evidence="ECO:0000305" FT CONFLICT 175 FT /note="C -> Y (in Ref. 1; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 239 FT /note="F -> L (in Ref. 1; no nucleotide entry)" FT /evidence="ECO:0000305" FT STRAND 33..35 FT /evidence="ECO:0007829|PDB:1R9O" FT TURN 37..39 FT /evidence="ECO:0007829|PDB:5X23" FT HELIX 42..44 FT /evidence="ECO:0007829|PDB:5X23" FT HELIX 47..61 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 63..71 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 73..77 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 80..87 FT /evidence="ECO:0007829|PDB:1R9O" FT TURN 88..94 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:5A5J" FT TURN 105..107 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 111..114 FT /evidence="ECO:0007829|PDB:5A5I" FT HELIX 117..131 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:5X23" FT HELIX 141..157 FT /evidence="ECO:0007829|PDB:1R9O" FT TURN 158..161 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 167..183 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 192..208 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 211..214 FT /evidence="ECO:0007829|PDB:5X23" FT HELIX 216..218 FT /evidence="ECO:0007829|PDB:5X23" FT HELIX 222..224 FT /evidence="ECO:0007829|PDB:5W0C" FT TURN 227..229 FT /evidence="ECO:0007829|PDB:5A5J" FT HELIX 230..253 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 263..274 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 275..277 FT /evidence="ECO:0007829|PDB:5X23" FT HELIX 284..315 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 317..330 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 339..344 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 346..359 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 374..376 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 386..389 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 392..395 FT /evidence="ECO:0007829|PDB:1R9O" FT TURN 398..400 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 401..403 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 409..412 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 415..417 FT /evidence="ECO:0007829|PDB:1OG5" FT HELIX 431..433 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 438..455 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 456..462 FT /evidence="ECO:0007829|PDB:1R9O" FT HELIX 464..466 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 475..477 FT /evidence="ECO:0007829|PDB:1R9O" FT STRAND 485..489 FT /evidence="ECO:0007829|PDB:1R9O" SQ SEQUENCE 490 AA; 55628 MW; 4FDFC395303A4E3E CRC64; MDSLVVLVLC LSCLLLLSLW RQSSGRGKLP PGPTPLPVIG NILQIGIKDI SKSLTNLSKV YGPVFTLYFG LKPIVVLHGY EAVKEALIDL GEEFSGRGIF PLAERANRGF GIVFSNGKKW KEIRRFSLMT LRNFGMGKRS IEDRVQEEAR CLVEELRKTK ASPCDPTFIL GCAPCNVICS IIFHKRFDYK DQQFLNLMEK LNENIKILSS PWIQICNNFS PIIDYFPGTH NKLLKNVAFM KSYILEKVKE HQESMDMNNP QDFIDCFLMK MEKEKHNQPS EFTIESLENT AVDLFGAGTE TTSTTLRYAL LLLLKHPEVT AKVQEEIERV IGRNRSPCMQ DRSHMPYTDA VVHEVQRYID LLPTSLPHAV TCDIKFRNYL IPKGTTILIS LTSVLHDNKE FPNPEMFDPH HFLDEGGNFK KSKYFMPFSA GKRICVGEAL AGMELFLFLT SILQNFNLKS LVDPKNLDTT PVVNGFASVP PFYQLCFIPV //