CP2C8_HUMAN
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 03-AUG-2022, entry version 225.
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 [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 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 [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 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 [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};
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: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 [NADPH--
CC 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 (4-
CC hydroxylation) {ECO:0000269|PubMed:11093772};
CC Vmax=6.2 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z,17Z)-
CC eicosapentaenoate (epoxygenation) {ECO:0000269|PubMed:15766564};
CC Vmax=4.6 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate (epoxygenation) {ECO:0000269|PubMed:15766564};
CC Vmax=2.18 pmol/min/pmol enzyme toward paclitaxel
CC {ECO:0000269|PubMed:26427316};
CC Vmax=11.30 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 ---------------------------------------------------------------------------
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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; 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; 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; 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; 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; DB08918; Levomilnacipran.
DR DrugBank; DB00451; Levothyroxine.
DR DrugBank; DB04725; Licofelone.
DR DrugBank; DB00281; Lidocaine.
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; 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; 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; 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; 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; 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; 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; 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; DB00359; Sulfadiazine.
DR DrugBank; DB06729; Sulfaphenazole.
DR DrugBank; DB01138; Sulfinpyrazone.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB00799; Tazarotene.
DR DrugBank; DB09256; Tegafur.
DR DrugBank; DB01079; Tegaserod.
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; 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; P10632; -.
DR PeptideAtlas; P10632; -.
DR PRIDE; P10632; -.
DR ProteomicsDB; 52621; -. [P10632-1]
DR ProteomicsDB; 52622; -. [P10632-2]
DR Antibodypedia; 3013; 218 antibodies from 33 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 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 Orphanet; 529828; Prediction of enzalutamide toxicity.
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; VVAKPHF; -.
DR OrthoDB; 702827at2759; -.
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 1069 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 110 other tissues.
DR ExpressionAtlas; P10632; baseline and differential.
DR Genevisible; P10632; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO: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:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
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 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; 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 African-
FT Americans; increases intrinsic clearance of paclitaxel;
FT decreases affinity for amodiaquine; increases enzymatic
FT activity with amodiaquine as substrate; 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
