ID CP2C8_HUMAN Reviewed; 490 AA. AC P10632; A8K9N8; B0AZN2; B7Z1F6; Q5VX93; Q8WWB1; Q9UCZ9; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 2. DT 27-MAR-2024, entry version 234. DE RecName: Full=Cytochrome P450 2C8 {ECO:0000303|PubMed:26427316}; DE EC=1.14.14.1 {ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:14559847}; DE AltName: Full=CYPIIC8; DE AltName: Full=Cytochrome P450 IIC2; DE AltName: Full=Cytochrome P450 MP-12; DE AltName: Full=Cytochrome P450 MP-20; DE AltName: Full=Cytochrome P450 form 1; DE AltName: Full=S-mephenytoin 4-hydroxylase; GN Name=CYP2C8 {ECO:0000303|PubMed:7574697, ECO:0000312|HGNC:HGNC:2622}; 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 MET-264. RC TISSUE=Liver; RX PubMed=3500169; DOI=10.1016/s0021-9258(18)47697-1; RA Okino S.T., Quattrochi L.C., Pendurthi U.R., McBride O.W., Tukey R.H.; RT "Characterization of multiple human cytochrome P-450 1 cDNAs. The RT chromosomal localization of the gene and evidence for alternate RNA RT splicing."; RL J. Biol. Chem. 262:16072-16079(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; 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 [MRNA] (ISOFORM 1), AND VARIANT MET-264. RX PubMed=2009263; DOI=10.1021/bi00227a012; RA Romkes M., Faletto M.B., Blaisdell J.A., Raucy J.L., Goldstein J.A.; RT "Cloning and expression of complementary DNAs for multiple members of the RT human cytochrome P450IIC subfamily."; RL Biochemistry 30:3247-3255(1991). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS RP LYS-139 AND ARG-399. RC TISSUE=Liver, and 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 [GENOMIC DNA], AND VARIANTS LYS-139; VAL-244; MET-264; RP PHE-269 AND ARG-399. RG NIEHS SNPs program; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56. RC TISSUE=Blood; RX PubMed=1707679; DOI=10.1016/0167-4781(91)90138-c; RA Ged C., Beaune P.; RT "Isolation of the human cytochrome P-450 IIC8 gene: multiple glucocorticoid RT responsive elements in the 5' region."; RL Biochim. Biophys. Acta 1088:433-435(1991). RN [10] RP PROTEIN SEQUENCE OF 2-15, NUCLEOTIDE SEQUENCE [MRNA] OF 6-490, FUNCTION, RP CATALYTIC ACTIVITY, PATHWAY, AND VARIANT LEU-411. 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 [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-490 (ISOFORM 1), AND VARIANTS ASP-154; RP LYS-193; ARG-249 AND LEU-411. RC TISSUE=Liver; 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 [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-382 (ISOFORM 1), AND VARIANT LYS-139. RX PubMed=2729895; DOI=10.1111/j.1469-1809.1989.tb01119.x; RA Shephard E.A., Phillips I.R., Santisteban I., Palmer C.N., Povey S.; RT "Cloning, expression and chromosomal localization of a member of the human RT cytochrome P450IIC gene sub-family."; RL Ann. Hum. Genet. 53:23-31(1989). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 281-490 (ISOFORM 1), AND VARIANT ARG-399. RX PubMed=2216732; DOI=10.1093/nar/18.18.5550; RA Kolyada A.Y.; RT "Sequence of a human liver cytochrome P-450 cDNA clone."; RL Nucleic Acids Res. 18:5550-5550(1990). RN [14] RP POLYMORPHISM. RX PubMed=15365880; DOI=10.1007/s10038-004-0188-6; RA Ishikawa C., Ozaki H., Nakajima T., Ishii T., Kanai S., Anjo S., Shirai K., RA Inoue I.; RT "A frameshift variant of CYP2C8 was identified in a patient who suffered RT from rhabdomyolysis after administration of cerivastatin."; RL J. Hum. Genet. 49:582-585(2004). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY. RX PubMed=11093772; DOI=10.1124/mol.58.6.1341; RA Marill J., Cresteil T., Lanotte M., Chabot G.G.; RT "Identification of human cytochrome P450s involved in the formation of all- RT trans-retinoic acid principal metabolites."; RL Mol. Pharmacol. 58:1341-1348(2000). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=14559847; RA Lee A.J., Conney A.H., Zhu B.T.; RT "Human cytochrome P450 3A7 has a distinct high catalytic activity for the RT 16alpha-hydroxylation of estrone but not 17beta-estradiol."; RL Cancer Res. 63:6532-6536(2003). RN [17] 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 [18] 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, AND IDENTIFICATION BY RP 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 [20] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 28-490. RX PubMed=14676196; DOI=10.1074/jbc.m312516200; RA Schoch G.A., Yano J.K., Wester M.R., Griffin K.J., Stout C.D., RA Johnson E.F.; RT "Structure of human microsomal cytochrome P450 2C8. Evidence for a RT peripheral fatty acid binding site."; RL J. Biol. Chem. 279:9497-9503(2004). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 28-490 IN COMPLEX WITH RP INHIBITORS, AND SUBSTRATE-BINDING SITES. RX PubMed=18413310; DOI=10.1074/jbc.m802180200; RA Schoch G.A., Yano J.K., Sansen S., Dansette P.M., Stout C.D., Johnson E.F.; RT "Determinants of cytochrome P450 2C8 substrate binding: structures of RT complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic RT acid."; RL J. Biol. Chem. 283:17227-17237(2008). RN [22] RP VARIANTS LYS-139; PHE-269 AND ARG-399. RX PubMed=11668219; DOI=10.1097/00008571-200110000-00006; RA Dai D., Zeldin D.C., Blaisdell J.A., Chanas B., Coulter S.J., RA Ghanayem B.I., Goldstein J.A.; RT "Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug RT paclitaxel and arachidonic acid."; RL Pharmacogenetics 11:597-607(2001). RN [23] RP VARIANTS LYS-139; MET-264; PHE-269; SER-390 AND ARG-399. RX PubMed=12429347; DOI=10.1016/s0006-2952(02)01354-0; RA Bahadur N., Leathart J.B., Mutch E., Steimel-Crespi D., Dunn S.A., RA Gilissen R., Houdt J.V., Hendrickx J., Mannens G., Bohets H., RA Williams F.M., Armstrong M., Crespi C.L., Daly A.K.; RT "CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel RT 6alpha-hydroxylase activity in human liver microsomes."; RL Biochem. Pharmacol. 64:1579-1589(2002). RN [24] RP VARIANTS LYS-139; MET-264; PHE-269 AND ARG-399. 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 [25] RP CHARACTERIZATION OF VARIANTS LYS-139; SER-171; GLY-186; MET-223; PRO-238; RP ARG-247; MET-264; PHE-269; ASN-383; ARG-399 AND VAL-461 DEL, FUNCTION, RP BIOPHYSICOCHEMICAL PROPERTIES, AND POLYMORPHISM. RX PubMed=26427316; DOI=10.1016/j.dmpk.2015.07.003; RA Tsukada C., Saito T., Maekawa M., Mano N., Oda A., Hirasawa N., RA Hiratsuka M.; RT "Functional characterization of 12 allelic variants of CYP2C8 by assessment RT of paclitaxel 6alpha-hydroxylation and amodiaquine N-deethylation."; RL Drug Metab. Pharmacokinet. 30:366-373(2015). CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of CC various endogenous substrates, including fatty acids, steroid hormones CC and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, CC PubMed:15766564, PubMed:19965576). Mechanistically, uses molecular CC oxygen inserting one oxygen atom into a substrate, and reducing the CC second into a water molecule, with two electrons provided by NADPH via CC cytochrome P450 reductase (NADPH--hemoprotein reductase) CC (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, CC PubMed:19965576). Primarily catalyzes the epoxidation of double bonds CC of polyunsaturated fatty acids (PUFA) with a preference for the last CC double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). CC Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all CC trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). CC Displays 16-alpha hydroxylase activity toward estrogen steroid CC hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). CC Plays a role in the oxidative metabolism of xenobiotics. It is the CC principal enzyme responsible for the metabolism of the anti-cancer drug CC paclitaxel (taxol) (PubMed:26427316). {ECO:0000269|PubMed:11093772, CC ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15766564, CC ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:26427316, CC ECO:0000269|PubMed:7574697}. 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:11093772, ECO:0000269|PubMed:14559847}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; CC Evidence={ECO:0000305|PubMed:11093772}; 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 ECO:0000305|PubMed:15766564}; 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 ECO:0000305|PubMed:15766564}; 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}; 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:19965576}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; CC Evidence={ECO:0000305|PubMed:19965576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)- CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:39783, 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:76635; Evidence={ECO:0000269|PubMed:19965576}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39784; CC Evidence={ECO:0000305|PubMed:19965576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)- CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:136410; Evidence={ECO:0000269|PubMed:19965576}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; CC Evidence={ECO:0000305|PubMed:19965576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced CC [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)- CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:52124, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:136411; Evidence={ECO:0000269|PubMed:19965576}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52125; CC Evidence={ECO:0000305|PubMed:19965576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein CC reductase] = all-trans-4-hydroxyretinoate + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51984, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134178; CC Evidence={ECO:0000269|PubMed:11093772}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985; CC Evidence={ECO:0000305|PubMed:11093772}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] CC = 16alpha,17beta-estriol + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:47332, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16469, ChEBI:CHEBI:27974, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:14559847}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47333; CC Evidence={ECO:0000305|PubMed:14559847}; CC -!- CATALYTIC ACTIVITY: CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = CC 16alpha-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:47204, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:14559847}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47205; CC Evidence={ECO:0000305|PubMed:14559847}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=50 uM for all-trans-retinoate (4-hydroxylation) CC {ECO:0000269|PubMed:11093772}; CC KM=5.4 uM for (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate (epoxygenation) CC {ECO:0000269|PubMed:15766564}; CC KM=6 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (epoxygenation) CC {ECO:0000269|PubMed:15766564}; CC KM=7.18 uM for paclitaxel {ECO:0000269|PubMed:26427316}; CC KM=1.35 uM for amodiaquine {ECO:0000269|PubMed:26427316}; CC Vmax=1211 pmol/min/nmol enzyme toward all-trans-retinoate CC (4-hydroxylation) {ECO:0000269|PubMed:11093772}; CC Vmax=6.2 nmol/min/nmol enzyme toward CC (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate (epoxygenation) CC {ECO:0000269|PubMed:15766564}; CC Vmax=4.6 nmol/min/nmol enzyme toward CC (5Z,8Z,11Z,14Z)-eicosatetraenoate (epoxygenation) CC {ECO:0000269|PubMed:15766564}; CC Vmax=2.18 pmol/min/pmol enzyme toward paclitaxel CC {ECO:0000269|PubMed:26427316}; CC Vmax=11.3 pmol/min/pmol enzyme toward amodiaquine CC {ECO:0000269|PubMed:26427316}; CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:14559847}. CC -!- PATHWAY: Lipid metabolism; arachidonate metabolism. CC {ECO:0000269|PubMed:15766564, ECO:0000269|PubMed:19965576, CC ECO:0000269|PubMed:7574697}. CC -!- PATHWAY: Cofactor metabolism; retinol metabolism. CC {ECO:0000269|PubMed:11093772}. CC -!- INTERACTION: CC P10632; P13473-2: LAMP2; NbExp=3; IntAct=EBI-2951522, EBI-21591415; CC P10632; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-2951522, EBI-5280197; CC P10632; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-2951522, EBI-2623095; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral CC membrane protein. Microsome membrane; Peripheral membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P10632-1; Sequence=Displayed; CC Name=2; CC IsoId=P10632-2; Sequence=VSP_043306, VSP_043307; CC -!- INDUCTION: By phenobarbital. CC -!- POLYMORPHISM: Several alleles are found in the human population, CC contributing to interindividual variations in the therapeutic efficacy CC and toxicity of a myriad of drugs such as paclitaxel or amodiaquine. CC The allele shown here is CYP2C8*1 (PubMed:26427316). CYP2C8 genetic CC variations are associated with altered drug metabolism and adverse drug CC effects including acute rhabdomyolysis after cerivastatin use CC [MIM:618018]. {ECO:0000269|PubMed:15365880, CC ECO:0000269|PubMed:26427316}. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- CAUTION: Alternative splicing has been shown to occur but the shorter CC forms are believed to be non-functional. {ECO:0000305}. CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium; CC Note=CYP2C8 alleles; CC URL="https://www.pharmvar.org/gene/CYP2C8"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cyp2c8/"; 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; M17397; AAA35739.1; -; mRNA. DR EMBL; M17398; AAA35740.1; -; mRNA. DR EMBL; Y00498; CAA68550.1; -; mRNA. DR EMBL; AK292753; BAF85442.1; -; mRNA. DR EMBL; AK293328; BAH11492.1; -; mRNA. DR EMBL; AK315823; BAF98714.1; -; mRNA. DR EMBL; AY514490; AAR89907.1; -; Genomic_DNA. DR EMBL; AL359672; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW50018.1; -; Genomic_DNA. DR EMBL; BC020596; AAH20596.1; -; mRNA. DR EMBL; X54807; CAA38578.1; -; Genomic_DNA. DR EMBL; M21941; AAA52160.1; -; mRNA. DR EMBL; M21942; AAA52161.1; -; mRNA. DR EMBL; X51535; CAA35915.1; -; mRNA. DR CCDS; CCDS55721.1; -. [P10632-2] DR CCDS; CCDS7438.1; -. [P10632-1] DR PIR; A29782; A29782. DR RefSeq; NP_000761.3; NM_000770.3. [P10632-1] DR RefSeq; NP_001185782.1; NM_001198853.1. DR RefSeq; NP_001185783.1; NM_001198854.1. [P10632-2] DR RefSeq; NP_001185784.1; NM_001198855.1. DR PDB; 1PQ2; X-ray; 2.70 A; A/B=19-490. DR PDB; 2NNH; X-ray; 2.60 A; A/B=28-490. DR PDB; 2NNI; X-ray; 2.80 A; A=28-490. DR PDB; 2NNJ; X-ray; 2.28 A; A=28-490. DR PDB; 2VN0; X-ray; 2.70 A; A=28-490. DR PDBsum; 1PQ2; -. DR PDBsum; 2NNH; -. DR PDBsum; 2NNI; -. DR PDBsum; 2NNJ; -. DR PDBsum; 2VN0; -. DR AlphaFoldDB; P10632; -. DR SMR; P10632; -. DR BioGRID; 107936; 19. DR IntAct; P10632; 13. DR STRING; 9606.ENSP00000360317; -. DR BindingDB; P10632; -. DR ChEMBL; CHEMBL3721; -. DR DrugBank; DB08607; (5R)-5-(4-{[(2R)-6-HYDROXY-2,5,7,8-TETRAMETHYL-3,4-DIHYDRO-2H-CHROMEN-2-YL]METHOXY}BENZYL)-1,3-THIAZOLIDINE-2,4-DIONE. DR DrugBank; DB08496; (R)-warfarin. DR DrugBank; DB14055; (S)-Warfarin. DR DrugBank; DB12001; Abemaciclib. DR DrugBank; DB05812; Abiraterone. DR DrugBank; DB15568; Adagrasib. DR DrugBank; DB00918; Almotriptan. DR DrugBank; DB12015; Alpelisib. DR DrugBank; DB01424; Aminophenazone. DR DrugBank; DB01118; Amiodarone. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00381; Amlodipine. DR DrugBank; DB00613; Amodiaquine. DR DrugBank; DB01060; Amoxicillin. DR DrugBank; DB01217; Anastrozole. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB11901; Apalutamide. DR DrugBank; DB06605; Apixaban. DR DrugBank; DB00714; Apomorphine. DR DrugBank; DB01072; Atazanavir. DR DrugBank; DB01076; Atorvastatin. DR DrugBank; DB11995; Avatrombopag. DR DrugBank; DB00972; Azelastine. DR DrugBank; DB08822; Azilsartan medoxomil. DR DrugBank; DB12781; Balaglitazone. DR DrugBank; DB13997; Baloxavir marboxil. DR DrugBank; DB05015; Belinostat. DR DrugBank; DB16703; Belumosudil. DR DrugBank; DB06770; Benzyl alcohol. DR DrugBank; DB05229; Beraprost. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB00307; Bexarotene. DR DrugBank; DB01393; Bezafibrate. DR DrugBank; DB13746; Bioallethrin. DR DrugBank; DB16536; Birch bark extract. DR DrugBank; DB06616; Bosutinib. DR DrugBank; DB12267; Brigatinib. DR DrugBank; DB12151; Brincidofovir. DR DrugBank; DB01222; Budesonide. DR DrugBank; DB00921; Buprenorphine. DR DrugBank; DB06772; Cabazitaxel. DR DrugBank; DB08875; Cabozantinib. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB13919; Candesartan. DR DrugBank; DB00796; Candesartan cilexetil. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB08502; Capravirine. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB00482; Celecoxib. DR DrugBank; DB06119; Cenobamate. DR DrugBank; DB00439; Cerivastatin. DR DrugBank; DB00608; Chloroquine. DR DrugBank; DB00169; Cholecalciferol. DR DrugBank; DB09201; Ciglitazone. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB00604; Cisapride. DR DrugBank; DB12499; Clascoterone. DR DrugBank; DB00845; Clofazimine. DR DrugBank; DB00758; Clopidogrel. DR DrugBank; DB00257; Clotrimazole. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB00907; Cocaine. DR DrugBank; DB01394; Colchicine. DR DrugBank; DB05219; Crisaborole. DR DrugBank; DB00531; Cyclophosphamide. DR DrugBank; DB08912; Dabrafenib. DR DrugBank; DB00250; Dapsone. DR DrugBank; DB09183; Dasabuvir. DR DrugBank; DB01609; Deferasirox. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB14649; Dexamethasone acetate. DR DrugBank; DB09213; Dexibuprofen. DR DrugBank; DB00829; Diazepam. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB00255; Diethylstilbestrol. DR DrugBank; DB00343; Diltiazem. DR DrugBank; DB01184; Domperidone. DR DrugBank; DB00625; Efavirenz. DR DrugBank; DB11979; Elagolix. DR DrugBank; DB15444; Elexacaftor. DR DrugBank; DB06210; Eltrombopag. DR DrugBank; DB13874; Enasidenib. DR DrugBank; DB08899; Enzalutamide. DR DrugBank; DB00530; Erlotinib. 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; DB00402; Eszopiclone. DR DrugBank; DB00977; Ethinylestradiol. DR DrugBank; DB00973; Ezetimibe. DR DrugBank; DB12466; Favipiravir. DR DrugBank; DB04854; Febuxostat. DR DrugBank; DB01023; Felodipine. DR DrugBank; DB01039; Fenofibrate. DR DrugBank; DB16165; Finerenone. DR DrugBank; DB00544; Fluorouracil. DR DrugBank; DB13867; Fluticasone. DR DrugBank; DB08906; Fluticasone furoate. DR DrugBank; DB00588; Fluticasone propionate. DR DrugBank; DB01095; Fluvastatin. DR DrugBank; DB01241; Gemfibrozil. DR DrugBank; DB01645; Genistein. DR DrugBank; DB11978; Glasdegib. DR DrugBank; DB01218; Halofantrine. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB14538; Hydrocortisone aceponate. DR DrugBank; DB14539; Hydrocortisone acetate. DR DrugBank; DB14540; Hydrocortisone butyrate. DR DrugBank; DB14541; Hydrocortisone cypionate. DR DrugBank; DB14542; Hydrocortisone phosphate. DR DrugBank; DB14543; Hydrocortisone probutate. DR DrugBank; DB14545; Hydrocortisone succinate. DR DrugBank; DB14544; Hydrocortisone valerate. DR DrugBank; DB01611; Hydroxychloroquine. DR DrugBank; DB12471; Ibrexafungerp. DR DrugBank; DB01050; Ibuprofen. DR DrugBank; DB09054; Idelalisib. DR DrugBank; DB01181; Ifosfamide. DR DrugBank; DB00619; Imatinib. 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; DB00448; Lansoprazole. DR DrugBank; DB01259; Lapatinib. DR DrugBank; DB09078; Lenvatinib. DR DrugBank; DB12070; Letermovir. DR DrugBank; DB05667; Levoketoconazole. DR DrugBank; DB08918; Levomilnacipran. DR DrugBank; DB00451; Levothyroxine. DR DrugBank; DB04725; Licofelone. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB17083; Linzagolix. DR DrugBank; DB01583; Liotrix. DR DrugBank; DB09198; Lobeglitazone. DR DrugBank; DB06448; Lonafarnib. DR DrugBank; DB00836; Loperamide. DR DrugBank; DB00455; Loratadine. DR DrugBank; DB12130; Lorlatinib. DR DrugBank; DB00678; Losartan. DR DrugBank; DB00227; Lovastatin. DR DrugBank; DB09280; Lumacaftor. DR DrugBank; DB15935; Lumasiran. DR DrugBank; DB06077; Lumateperone. DR DrugBank; DB08932; Macitentan. DR DrugBank; DB14921; Mavacamten. DR DrugBank; DB14009; Medical Cannabis. DR DrugBank; DB00603; Medroxyprogesterone acetate. DR DrugBank; DB00784; Mefenamic acid. DR DrugBank; DB00814; Meloxicam. DR DrugBank; DB00170; Menadione. DR DrugBank; DB00532; Mephenytoin. DR DrugBank; DB01357; Mestranol. DR DrugBank; DB00333; Methadone. 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; DB00764; Mometasone. DR DrugBank; DB14512; Mometasone furoate. DR DrugBank; DB00471; Montelukast. DR DrugBank; DB00295; Morphine. DR DrugBank; DB06510; Muraglitazar. DR DrugBank; DB00688; Mycophenolate mofetil. DR DrugBank; DB01024; Mycophenolic acid. DR DrugBank; DB00486; Nabilone. DR DrugBank; DB00788; Naproxen. DR DrugBank; DB09199; Netoglitazone. DR DrugBank; DB00622; Nicardipine. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB01115; Nifedipine. DR DrugBank; DB04868; Nilotinib. DR DrugBank; DB06712; Nilvadipine. DR DrugBank; DB06670; Odanacatib. DR DrugBank; DB09080; Olodaterol. DR DrugBank; DB16267; Olutasidenib. DR DrugBank; DB09296; Ombitasvir. DR DrugBank; DB00338; Omeprazole. DR DrugBank; DB11632; Opicapone. DR DrugBank; DB01062; Oxybutynin. DR DrugBank; DB12612; Ozanimod. DR DrugBank; DB01229; Paclitaxel. DR DrugBank; DB03796; Palmitic Acid. DR DrugBank; DB05467; Palovarotene. DR DrugBank; DB00617; Paramethadione. DR DrugBank; DB06589; Pazopanib. DR DrugBank; DB08922; Perospirone. DR DrugBank; DB00850; Perphenazine. DR DrugBank; DB00780; Phenelzine. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00946; Phenprocoumon. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB01132; Pioglitazone. DR DrugBank; DB00554; Piroxicam. DR DrugBank; DB08860; Pitavastatin. DR DrugBank; DB08901; Ponatinib. DR DrugBank; DB15822; Pralsetinib. DR DrugBank; DB14631; Prednisolone phosphate. DR DrugBank; DB00635; Prednisone. DR DrugBank; DB01032; Probenecid. DR DrugBank; DB00818; Propofol. DR DrugBank; DB00205; Pyrimethamine. DR DrugBank; DB04216; Quercetin. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB00468; Quinine. DR DrugBank; DB01129; Rabeprazole. DR DrugBank; DB00481; Raloxifene. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB11853; Relugolix. DR DrugBank; DB14761; Remdesivir. DR DrugBank; DB00912; Repaglinide. DR DrugBank; DB02709; Resveratrol. DR DrugBank; DB00615; Rifabutin. DR DrugBank; DB01045; Rifampicin. DR DrugBank; DB11753; Rifamycin. DR DrugBank; DB01201; Rifapentine. DR DrugBank; DB01220; Rifaximin. DR DrugBank; DB08864; Rilpivirine. DR DrugBank; DB08931; Riociguat. DR DrugBank; DB14840; Ripretinib. DR DrugBank; DB00503; Ritonavir. DR DrugBank; DB09200; Rivoglitazone. DR DrugBank; DB00533; Rofecoxib. DR DrugBank; DB00412; Rosiglitazone. DR DrugBank; DB04847; Roxadustat. DR DrugBank; DB12332; Rucaparib. DR DrugBank; DB00938; Salmeterol. DR DrugBank; DB12543; Samidorphan. DR DrugBank; DB01232; Saquinavir. DR DrugBank; DB00418; Secobarbital. DR DrugBank; DB01037; Selegiline. DR DrugBank; DB11362; Selexipag. DR DrugBank; DB15685; Selpercatinib. DR DrugBank; DB11689; Selumetinib. DR DrugBank; DB06739; Seratrodast. DR DrugBank; DB00641; Simvastatin. DR DrugBank; DB01261; Sitagliptin. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB15569; Sotorasib. DR DrugBank; DB00421; Spironolactone. DR DrugBank; DB09118; Stiripentol. DR DrugBank; DB00359; Sulfadiazine. DR DrugBank; DB06729; Sulfaphenazole. DR DrugBank; DB01138; Sulfinpyrazone. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB00799; Tazarotene. DR DrugBank; DB12020; Tecovirimat. DR DrugBank; DB09256; Tegafur. DR DrugBank; DB01079; Tegaserod. DR DrugBank; DB12095; Telotristat ethyl. DR DrugBank; DB15133; Tepotinib. DR DrugBank; DB00857; Terbinafine. DR DrugBank; DB00342; Terfenadine. DR DrugBank; DB08880; Teriflunomide. DR DrugBank; DB00624; Testosterone. DR DrugBank; DB13943; Testosterone cypionate. DR DrugBank; DB13944; Testosterone enanthate. DR DrugBank; DB13946; Testosterone undecanoate. DR DrugBank; DB00208; Ticlopidine. DR DrugBank; DB06137; Tirbanibulin. DR DrugBank; DB01124; Tolbutamide. DR DrugBank; DB01685; Topiroxostat. DR DrugBank; DB00214; Torasemide. DR DrugBank; DB08911; Trametinib. DR DrugBank; DB00374; Treprostinil. DR DrugBank; DB00755; Tretinoin. DR DrugBank; DB00897; Triazolam. DR DrugBank; DB12245; Triclabendazole. DR DrugBank; DB12808; Trifarotene. DR DrugBank; DB00347; Trimethadione. DR DrugBank; DB00440; Trimethoprim. DR DrugBank; DB00197; Troglitazone. DR DrugBank; DB13179; Troleandomycin. DR DrugBank; DB11652; Tucatinib. DR DrugBank; DB15328; Ubrogepant. DR DrugBank; DB11613; Velpatasvir. DR DrugBank; DB08881; Vemurafenib. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB08828; Vismodegib. DR DrugBank; DB09068; Vortioxetine. DR DrugBank; DB12026; Voxilaprevir. DR DrugBank; DB00682; Warfarin. DR DrugBank; DB00549; Zafirlukast. DR DrugBank; DB01198; Zopiclone. DR DrugCentral; P10632; -. DR GuidetoPHARMACOLOGY; 1325; -. DR SwissLipids; SLP:000001548; -. DR SwissLipids; SLP:000001616; -. [P10632-1] DR iPTMnet; P10632; -. DR PhosphoSitePlus; P10632; -. DR BioMuta; CYP2C8; -. DR DMDM; 117225; -. DR MassIVE; P10632; -. DR PaxDb; 9606-ENSP00000360317; -. DR PeptideAtlas; P10632; -. DR ProteomicsDB; 52621; -. [P10632-1] DR ProteomicsDB; 52622; -. [P10632-2] DR Antibodypedia; 3013; 252 antibodies from 34 providers. DR DNASU; 1558; -. DR Ensembl; ENST00000371270.6; ENSP00000360317.3; ENSG00000138115.15. [P10632-1] DR Ensembl; ENST00000535898.5; ENSP00000445062.1; ENSG00000138115.15. [P10632-2] DR GeneID; 1558; -. DR KEGG; hsa:1558; -. DR MANE-Select; ENST00000371270.6; ENSP00000360317.3; NM_000770.3; NP_000761.3. DR UCSC; uc001kkb.4; human. [P10632-1] DR AGR; HGNC:2622; -. DR CTD; 1558; -. DR DisGeNET; 1558; -. DR GeneCards; CYP2C8; -. DR HGNC; HGNC:2622; CYP2C8. DR HPA; ENSG00000138115; Tissue enriched (liver). DR MalaCards; CYP2C8; -. DR MIM; 601129; gene. DR MIM; 618018; phenotype. DR neXtProt; NX_P10632; -. DR OpenTargets; ENSG00000138115; -. DR PharmGKB; PA125; -. DR VEuPathDB; HostDB:ENSG00000138115; -. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000163696; -. DR HOGENOM; CLU_001570_22_2_1; -. DR InParanoid; P10632; -. DR OMA; SFTTTEW; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; P10632; -. DR TreeFam; TF352043; -. DR BRENDA; 1.14.14.1; 2681. DR PathwayCommons; P10632; -. 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; P10632; -. DR SignaLink; P10632; -. DR UniPathway; UPA00383; -. DR UniPathway; UPA00912; -. DR BioGRID-ORCS; 1558; 12 hits in 1149 CRISPR screens. DR ChiTaRS; CYP2C8; human. DR EvolutionaryTrace; P10632; -. DR GeneWiki; CYP2C8; -. DR GenomeRNAi; 1558; -. DR Pharos; P10632; Tchem. DR PRO; PR:P10632; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P10632; Protein. DR Bgee; ENSG00000138115; Expressed in right lobe of liver and 112 other cell types or tissues. DR ExpressionAtlas; P10632; 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: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:0101020; F:estrogen 16-alpha-hydroxylase 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: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:0008401; F:retinoic acid 4-hydroxylase activity; IDA:UniProtKB. 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:0002933; P:lipid hydroxylation; IDA:BHF-UCL. DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome. DR GO; GO:0097267; P:omega-hydroxylase P450 pathway; TAS:Reactome. DR GO; GO:0006082; P:organic acid metabolic process; IDA:BHF-UCL. DR GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL. DR GO; GO:0042573; P:retinoic acid metabolic process; IDA:UniProtKB. DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0008202; P:steroid 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:SF317; CYTOCHROME P450 2C8; 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; P10632; 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; Phosphoprotein; KW Reference proteome; Steroid metabolism. FT CHAIN 1..490 FT /note="Cytochrome P450 2C8" FT /id="PRO_0000051699" FT BINDING 100 FT /ligand="substrate" FT BINDING 204 FT /ligand="substrate" FT BINDING 241 FT /ligand="substrate" 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 MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..8 FT /note="MEPFVVLV -> MFLQPIAK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043306" FT VAR_SEQ 9..110 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043307" FT VARIANT 139 FT /note="R -> K (in allele CYP2C8*3; reduces enzymatic FT activity with paclitaxel as substrate; decreases intrinsic FT clearance of paclitaxel; reduces enzymatic activity with FT amodiaquine as substrate; dbSNP:rs11572080)" FT /evidence="ECO:0000269|PubMed:11668219, FT ECO:0000269|PubMed:12429347, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15469410, ECO:0000269|PubMed:26427316, FT ECO:0000269|PubMed:2729895, ECO:0000269|Ref.5" FT /id="VAR_012238" FT VARIANT 154 FT /note="E -> D" FT /evidence="ECO:0000269|PubMed:3196692" FT /id="VAR_001250" FT VARIANT 171 FT /note="G -> S (in allele CYP2C8*6; no effect on affinity or FT enzymatic activity with paclitaxel as substrate; decreases FT affinity for amodiaquine; reduces enzymatic activity with FT amodiaquine as substrate; decreases intrinsic clearance of FT amodiaquine; dbSNP:rs142886225)" FT /evidence="ECO:0000269|PubMed:26427316" FT /id="VAR_075541" FT VARIANT 186 FT /note="R -> G (in allele CYP2C8*8; increases affinity for FT paclitaxel; reduces enzymatic activity with paclitaxel as FT substrate; decreases intrinsic clearance of paclitaxel; FT reduces enzymatic activity with amodiaquine as substrate; FT decreases intrinsic clearance of amodiaquine; FT dbSNP:rs72558195)" FT /evidence="ECO:0000269|PubMed:26427316" FT /id="VAR_075542" FT VARIANT 193 FT /note="N -> K" FT /evidence="ECO:0000269|PubMed:3196692" FT /id="VAR_001251" FT VARIANT 223 FT /note="I -> M (in allele CYP2C8*13; reduces enzymatic FT activity with paclitaxel as substrate; decreases intrinsic FT clearance of paclitaxel; reduces enzymatic activity with FT amodiaquine as substrate; decreases intrinsic clearance of FT amodiaquine)" FT /evidence="ECO:0000269|PubMed:26427316" FT /id="VAR_075543" FT VARIANT 238 FT /note="A -> P (in allele CYP2C8*14; reduces enzymatic FT activity with paclitaxel as substrate; decreases intrinsic FT clearance of paclitaxel; dbSNP:rs188934928)" FT /evidence="ECO:0000269|PubMed:26427316" FT /id="VAR_075544" FT VARIANT 244 FT /note="I -> V (in dbSNP:rs11572102)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_018958" FT VARIANT 247 FT /note="K -> R (in allele CYP2C8*9; increases enzymatic FT activity with paclitaxel as substrate; reduces enzymatic FT activity with amodiaquine as substrate; decreases intrinsic FT clearance of amodiaquine; dbSNP:rs769460274)" FT /evidence="ECO:0000269|PubMed:26427316" FT /id="VAR_075545" FT VARIANT 249 FT /note="K -> R" FT /evidence="ECO:0000269|PubMed:3196692" FT /id="VAR_001252" FT VARIANT 264 FT /note="I -> M (in allele CYP2C8*4; reduces enzymatic FT activity with paclitaxel as substrate; decreases affinity FT for amodiaquine; dbSNP:rs1058930)" FT /evidence="ECO:0000269|PubMed:12429347, FT ECO:0000269|PubMed:15469410, ECO:0000269|PubMed:2009263, FT ECO:0000269|PubMed:26427316, ECO:0000269|PubMed:3500169, FT ECO:0000269|Ref.5" FT /id="VAR_011754" FT VARIANT 269 FT /note="I -> F (in allele CYP2C8*2; only found in FT African-Americans; increases intrinsic clearance of FT paclitaxel; decreases affinity for amodiaquine; increases FT enzymatic activity with amodiaquine as substrate; FT dbSNP:rs11572103)" FT /evidence="ECO:0000269|PubMed:11668219, FT ECO:0000269|PubMed:12429347, ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:26427316, ECO:0000269|Ref.5" FT /id="VAR_012239" FT VARIANT 383 FT /note="K -> N (in allele CYP2C8*10; reduces enzymatic FT activity with paclitaxel as substrate; reduces enzymatic FT activity with amodiaquine as substrate; decreases intrinsic FT clearance of amodiaquine)" FT /evidence="ECO:0000269|PubMed:26427316" FT /id="VAR_075546" FT VARIANT 390 FT /note="L -> S (in dbSNP:rs72558194)" FT /evidence="ECO:0000269|PubMed:12429347" FT /id="VAR_016947" FT VARIANT 399 FT /note="K -> R (in allele CYP2C8*3; reduces enzymatic FT activity with paclitaxel as substrate; decreases intrinsic FT clearance of paclitaxel; reduces enzymatic activity with FT amodiaquine as substrate; dbSNP:rs10509681)" FT /evidence="ECO:0000269|PubMed:11668219, FT ECO:0000269|PubMed:12429347, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15469410, ECO:0000269|PubMed:2216732, FT ECO:0000269|PubMed:26427316, ECO:0000269|Ref.5" FT /id="VAR_012240" FT VARIANT 411 FT /note="H -> L" FT /evidence="ECO:0000269|PubMed:3196692, FT ECO:0000269|PubMed:7574697" FT /id="VAR_001253" FT VARIANT 461 FT /note="Missing (in allele CYP2C8*12; increases enzymatic FT activity with paclitaxel as substrate; reduces enzymatic FT activity with amodiaquine as substrate; decreases intrinsic FT clearance of amodiaquine)" FT /evidence="ECO:0000269|PubMed:26427316" FT /id="VAR_075547" FT CONFLICT 54 FT /note="F -> L (in Ref. 12; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 67 FT /note="V -> L (in Ref. 12; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 76 FT /note="V -> C (in Ref. 12; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 82 FT /note="A -> S (in Ref. 8; AAH20596)" FT /evidence="ECO:0000305" FT CONFLICT 130 FT /note="T -> N (in Ref. 1; AAA35739/AAA35740 and 3; no FT nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 209 FT /note="N -> S (in Ref. 12; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 384..393 FT /note="GTTIMALLTS -> SFDNKIMLAA (in Ref. 1; AAA35740)" FT /evidence="ECO:0000305" FT CONFLICT 386 FT /note="T -> A (in Ref. 4; BAF85442)" FT /evidence="ECO:0000305" FT TURN 37..39 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 42..44 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:1PQ2" FT HELIX 50..61 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 63..69 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 72..77 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 80..87 FT /evidence="ECO:0007829|PDB:2NNJ" FT TURN 88..94 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 101..107 FT /evidence="ECO:0007829|PDB:2NNJ" FT TURN 111..113 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 117..130 FT /evidence="ECO:0007829|PDB:2NNJ" FT TURN 133..136 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 141..157 FT /evidence="ECO:0007829|PDB:2NNJ" FT TURN 158..161 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 167..182 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 192..208 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 212..218 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 220..225 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 227..252 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 263..273 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 284..298 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 300..315 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 317..330 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 339..344 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 346..359 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 374..376 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 386..389 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 391..395 FT /evidence="ECO:0007829|PDB:2NNJ" FT TURN 398..400 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 401..403 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 409..412 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 431..433 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 438..455 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 456..459 FT /evidence="ECO:0007829|PDB:2NNJ" FT HELIX 464..466 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 472..479 FT /evidence="ECO:0007829|PDB:2NNJ" FT STRAND 485..489 FT /evidence="ECO:0007829|PDB:2NNJ" SQ SEQUENCE 490 AA; 55825 MW; E920EB2084F477E1 CRC64; MEPFVVLVLC LSFMLLFSLW RQSCRRRKLP PGPTPLPIIG NMLQIDVKDI CKSFTNFSKV YGPVFTVYFG MNPIVVFHGY EAVKEALIDN GEEFSGRGNS PISQRITKGL GIISSNGKRW KEIRRFSLTT LRNFGMGKRS IEDRVQEEAH CLVEELRKTK ASPCDPTFIL GCAPCNVICS VVFQKRFDYK DQNFLTLMKR FNENFRILNS PWIQVCNNFP LLIDCFPGTH NKVLKNVALT RSYIREKVKE HQASLDVNNP RDFIDCFLIK MEQEKDNQKS EFNIENLVGT VADLFVAGTE TTSTTLRYGL LLLLKHPEVT AKVQEEIDHV IGRHRSPCMQ DRSHMPYTDA VVHEIQRYSD LVPTGVPHAV TTDTKFRNYL IPKGTTIMAL LTSVLHDDKE FPNPNIFDPG HFLDKNGNFK KSDYFMPFSA GKRICAGEGL ARMELFLFLT TILQNFNLKS VDDLKNLNTT AVTKGIVSLP PSYQICFIPV //