CP2C9_HUMAN
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 03-AUG-2022, entry version 233.
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 CYP2C9*2 CYS-144 AND CYP2C9*3 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 CYP2C9*2 CYS-144; CYS-358; CYP2C9*3 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 CYP2C9*4 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 CYP2C9*5 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 CYP2C9*11 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 [NADPH--
CC hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131975; Evidence={ECO:0000269|PubMed: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 [NADPH--
CC hemoprotein reductase] = (8S,9R)-epoxy-(5Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49928, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI: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 [NADPH--
CC hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131970; Evidence={ECO:0000269|PubMed: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 [NADPH--
CC hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131969; Evidence={ECO:0000269|PubMed: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 [NADPH--
CC hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131965; Evidence={ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed: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 [NADPH--
CC hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI: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 [NADPH--
CC hemoprotein reductase] = 8,9-epoxy-(5Z,11Z,14Z,17Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:52168, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC 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 [NADPH--
CC 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 [NADPH--
CC 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 [NADPH--
CC hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76634; Evidence={ECO:0000269|PubMed: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 [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:28744,
CC 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 [NADPH--
CC 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 [NADPH--
CC 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 [NADPH--
CC 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 [NADPH--
CC hemoprotein reductase] = 10-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:52296, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI: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] = 9(R)-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 [NADPH--
CC hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:39759, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76627; Evidence={ECO:0000269|PubMed: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 [NADPH--
CC 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 [NADPH--
CC hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:51472, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI: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 [NADPH--
CC hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:51480, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI: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 [NADPH--
CC hemoprotein reductase] = 13-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:52292, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI: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=210.30 pmol/min/pmol enzyme with losartan as substrate
CC {ECO:0000269|PubMed:25994031};
CC Vmax=29.1 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate (epoxidation) {ECO:0000269|PubMed:15766564};
CC Vmax=29.2 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate (epoxidation) {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; DB06736; Aceclofenac.
DR DrugBank; DB01418; Acenocoumarol.
DR DrugBank; DB00414; Acetohexamide.
DR DrugBank; DB14033; Acetyl sulfisoxazole.
DR DrugBank; DB00945; Acetylsalicylic acid.
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; DB01101; Capecitabine.
DR DrugBank; DB08502; Capravirine.
DR DrugBank; DB00564; Carbamazepine.
DR DrugBank; DB13406; Carbutamide.
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; 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; 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; 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; 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; 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; 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; DB00231; Temazepam.
DR DrugBank; DB00444; Teniposide.
DR DrugBank; DB00469; Tenoxicam.
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; DB00661; Verapamil.
DR DrugBank; DB06652; Vicriviroc.
DR DrugBank; DB01080; Vigabatrin.
DR DrugBank; DB08828; Vismodegib.
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; P11712; -.
DR PeptideAtlas; P11712; -.
DR PRIDE; P11712; -.
DR ProteomicsDB; 52801; -. [P11712-1]
DR Antibodypedia; 4244; 309 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 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 Orphanet; 413681; Prediction of toxicity or dose selection of oral antidiabetic drugs.
DR Orphanet; 413674; Prediction of toxicity or dose selection of vitamin K antagonists.
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; SVPPVYQ; -.
DR PhylomeDB; P11712; -.
DR TreeFam; TF352043; -.
DR BioCyc; MetaCyc:HS06458-MON; -.
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 1031 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 tissues.
DR ExpressionAtlas; P11712; baseline and differential.
DR Genevisible; P11712; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
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:cellular 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:0006082; P:organic acid metabolic process; IBA:GO_Central.
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 Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 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
