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Cytochrome P450 2C9 (EC 1.14.14.-) ((R)-limonene 6-monooxygenase) (EC 1.14.14.53) ((S)-limonene 6-monooxygenase) (EC 1.14.14.51) ((S)-limonene 7-monooxygenase) (EC 1.14.14.52) (CYPIIC9) (Cholesterol 25-hydroxylase) (EC 1.14.14.-) (Cytochrome P-450MP) (Cytochrome P450 MP-4) (Cytochrome P450 MP-8) (Cytochrome P450 PB-1) (S-mephenytoin 4-hydroxylase)

 CP2C9_HUMAN             Reviewed;         490 AA.
P11712; P11713; Q16756; Q16872; Q5VX92; Q6IRV8; Q8WW80;
01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
30-MAY-2000, sequence version 3.
13-FEB-2019, entry version 213.
RecName: Full=Cytochrome P450 2C9;
EC=1.14.14.- {ECO:0000305|PubMed:3243766};
AltName: Full=(R)-limonene 6-monooxygenase;
EC=1.14.14.53 {ECO:0000269|PubMed:11950794};
AltName: Full=(S)-limonene 6-monooxygenase;
EC=1.14.14.51 {ECO:0000269|PubMed:11950794};
AltName: Full=(S)-limonene 7-monooxygenase;
EC=1.14.14.52 {ECO:0000269|PubMed:11950794};
AltName: Full=CYPIIC9;
AltName: Full=Cholesterol 25-hydroxylase {ECO:0000303|PubMed:3079764};
EC=1.14.14.- {ECO:0000269|PubMed:21576599};
AltName: Full=Cytochrome P-450MP;
AltName: Full=Cytochrome P450 MP-4;
AltName: Full=Cytochrome P450 MP-8;
AltName: Full=Cytochrome P450 PB-1;
AltName: Full=S-mephenytoin 4-hydroxylase {ECO:0000303|PubMed:3079764};
Name=CYP2C9; Synonyms=CYP2C10;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT CYS-144.
PubMed=2827463;
Meehan R.R., Gosden J.R., Rout D., Hastie N.D., Friedberg T.,
Adesnik M., Buckland R., van Heyningen V., Fletcher J.M., Spurr N.K.,
Sweeney J., Wolf C.R.;
"Human cytochrome P-450 PB-1: a multigene family involved in
mephenytoin and steroid oxidations that maps to chromosome 10.";
Am. J. Hum. Genet. 42:26-37(1988).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT CYS-144.
PubMed=3697070; DOI=10.1093/nar/15.23.10053;
Kimura S., Pastewka J., Gelboin H.V., Gonzalez F.J.;
"cDNA and amino acid sequences of two members of the human P450IIC
gene subfamily.";
Nucleic Acids Res. 15:10053-10054(1987).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-144; HIS-150;
ARG-251; GLY-272; LEU-359 AND SER-489.
NIEHS SNPs program;
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Mammary gland;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15164054; DOI=10.1038/nature02462;
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 10.";
Nature 429:375-381(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
CYS-144.
TISSUE=Liver;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
NUCLEOTIDE SEQUENCE [MRNA] OF 4-490 (ISOFORM 1).
TISSUE=Liver;
PubMed=2963808; DOI=10.1093/oxfordjournals.jbchem.a122145;
Yasumori T., Kawano S., Nagata K., Shimada M., Yamazoe Y., Kato R.;
"Nucleotide sequence of a human liver cytochrome P-450 related to the
rat male specific form.";
J. Biochem. 102:1075-1082(1987).
[9]
NUCLEOTIDE SEQUENCE [MRNA] OF 6-490 (ISOFORM 1), AND VARIANTS CYS-358
AND ASP-417.
TISSUE=Liver;
PubMed=3032244; DOI=10.1021/bi00378a016;
Umbenhauer D.R., Martin M.V., Lloyd R.S., Guengerich F.P.;
"Cloning and sequence determination of a complementary DNA related to
human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase.";
Biochemistry 26:1094-1099(1987).
[10]
NUCLEOTIDE SEQUENCE [MRNA] OF 6-490 (ISOFORM 1), AND VARIANTS CYS-358
AND ASP-417.
PubMed=3196692; DOI=10.1021/bi00418a039;
Ged C., Umbenhauer D.R., Bellew T.M., Bork R.W., Srivastava P.K.,
Shinriki N., Lloyd R.S., Guengerich F.P.;
"Characterization of cDNAs, mRNAs, and proteins related to human liver
microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase.";
Biochemistry 27:6929-6940(1988).
[11]
NUCLEOTIDE SEQUENCE [MRNA] OF 14-490 (ISOFORM 1).
PubMed=1445376;
Ohgiya S., Komori M., Ohi H., Shiramatsu K., Shinriki N., Kamataki T.;
"Six-base deletion occurring in messages of human cytochrome P-450 in
the CYP2C subfamily results in reduction of tolbutamide hydroxylase
activity.";
Biochem. Int. 27:1073-1081(1992).
[12]
PROTEIN SEQUENCE OF 1-29, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
PROPERTIES, AND CHARACTERIZATION.
PubMed=3079764;
Shimada T., Misono K.S., Guengerich F.P.;
"Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a
prototype of genetic polymorphism in oxidative drug metabolism.
Purification and characterization of two similar forms involved in the
reaction.";
J. Biol. Chem. 261:909-921(1986).
[13]
PROTEIN SEQUENCE OF 1-25, AND CATALYTIC ACTIVITY.
PubMed=3243766;
Komori M., Hashizume T., Ohi H., Miura T., Kitada M., Nagashima K.,
Kamataki T.;
"Cytochrome P-450 in human liver microsomes: high-performance liquid
chromatographic isolation of three forms and their characterization.";
J. Biochem. 104:912-916(1988).
[14]
PARTIAL PROTEIN SEQUENCE.
PubMed=1857342;
Srivastava P.K., Yun C.H., Beaune P.H., Ged C., Guengerich F.P.;
"Separation of human liver microsomal tolbutamide hydroxylase and (S)-
mephenytoin 4'-hydroxylase cytochrome P-450 enzymes.";
Mol. Pharmacol. 40:69-79(1991).
[15]
PROTEIN SEQUENCE OF 1-9; 21-157; 169-249; 264-424; 426-476 AND
484-487.
PubMed=8809086; DOI=10.1006/abbi.1996.0414;
Haining R.L., Hunter A.P., Veronese M.E., Trager W.F., Rettie A.E.;
"Allelic variants of human cytochrome P450 2C9: baculovirus-mediated
expression, purification, structural characterization, substrate
stereoselectivity, and prochiral selectivity of the wild-type and
I359L mutant forms.";
Arch. Biochem. Biophys. 333:447-458(1996).
[16]
PROTEIN SEQUENCE OF 1-20.
PubMed=8215449; DOI=10.1006/abbi.1993.1536;
Sandhu P., Baba T., Guengerich F.P.;
"Expression of modified cytochrome P450 2C10 (2C9) in Escherichia
coli, purification, and reconstitution of catalytic activity.";
Arch. Biochem. Biophys. 306:443-450(1993).
[17]
CATALYTIC ACTIVITY.
PubMed=11950794; DOI=10.1124/dmd.30.5.602;
Miyazawa M., Shindo M., Shimada T.;
"Metabolism of (+)- and (-)-limonenes to respective carveols and
perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes.";
Drug Metab. Dispos. 30:602-607(2002).
[18]
CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
PubMed=21576599; DOI=10.1194/jlr.M014084;
Honda A., Miyazaki T., Ikegami T., Iwamoto J., Maeda T., Hirayama T.,
Saito Y., Teramoto T., Matsuzaki Y.;
"Cholesterol 25-hydroxylation activity of CYP3A.";
J. Lipid Res. 52:1509-1516(2011).
[19]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[20]
X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 30-490.
PubMed=12861225; DOI=10.1038/nature01862;
Williams P.A., Cosme J., Ward A., Angove H.C., Matak-Vinkovic D.,
Jhoti H.;
"Crystal structure of human cytochrome P450 2C9 with bound warfarin.";
Nature 424:464-468(2003).
[21]
VARIANTS CYP2C9*2 CYS-144 AND CYP2C9*3 LEU-359.
PubMed=8946475;
Stubbins M.J., Harries L.W., Smith G., Tarbit M.H., Wolf C.R.;
"Genetic analysis of the human cytochrome P450 CYP2C9 locus.";
Pharmacogenetics 6:429-439(1996).
[22]
VARIANTS CYP2C9*2 CYS-144; CYS-358; CYP2C9*3 LEU-359 AND ASP-417.
PubMed=9110362;
Bhasker C.R., Miners J.O., Coulter S., Birkett D.J.;
"Allelic and functional variability of cytochrome P4502C9.";
Pharmacogenetics 7:51-58(1997).
[23]
VARIANT CYP2C9*4 THR-359.
PubMed=10739176; DOI=10.1097/00008571-200002000-00011;
Imai J., Ieiri I., Mamiya K., Miyahara S., Furuumi H., Nanba E.,
Yamane M., Fukumaki Y., Ninomiya H., Tashiro N., Otsubo K.,
Higuchi S.;
"Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese
epileptic patients: genetic analysis of the CYP2C9 locus.";
Pharmacogenetics 10:85-89(2000).
[24]
VARIANT CYP2C9*5 GLU-360.
PubMed=11455026;
Dickmann L.J., Rettie A.E., Kneller M.B., Kim R.B., Wood A.J.,
Stein C.M., Wilkinson G.R., Schwarz U.I.;
"Identification and functional characterization of a new CYP2C9
variant (CYP2C9*5) expressed among African Americans.";
Mol. Pharmacol. 60:382-387(2001).
[25]
VARIANT CYP2C9*11 TRP-335.
PubMed=11926893; DOI=10.1001/jama.287.13.1690;
Higashi M.K., Veenstra D.L., Kondo L.M., Wittkowsky A.K.,
Srinouanprachanh S.L., Farin F.M., Rettie A.E.;
"Association between CYP2C9 genetic variants and anticoagulation-
related outcomes during warfarin therapy.";
JAMA 287:1690-1698(2002).
[26]
VARIANTS CYS-144; HIS-150; ARG-251; TRP-335; LEU-359; GLU-360 AND
PRO-413.
PubMed=15469410; DOI=10.1517/14622416.5.7.895;
Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q.,
McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
"Genetic variation in eleven phase I drug metabolism genes in an
ethnically diverse population.";
Pharmacogenomics 5:895-931(2004).
[27]
VARIANT LEU-125.
PubMed=21451434; DOI=10.1097/FPC.0b013e328344c340;
Ciccacci C., Falconi M., Paolillo N., Oteri F., Forte V., Novelli G.,
Desideri A., Borgiani P.;
"Characterization of a novel CYP2C9 gene mutation and structural
bioinformatic protein analysis in a warfarin hypersensitive patient.";
Pharmacogenet. Genomics 21:344-346(2011).
[28]
VARIANT HIS-204.
PubMed=23582453; DOI=10.1016/j.thromres.2013.03.019;
Nahar R., Dube D., Parakh R., Deb R., Saxena R., Singh T.P.,
Verma I.C.;
"Implication of novel CYP2C9*57 (p.Asn204His) variant in coumarin
hypersensitivity.";
Thromb. Res. 131:535-539(2013).
[29]
VARIANT HIS-125.
PubMed=24956244; DOI=10.2217/pgs.14.47;
Lee Y.M., Eggen J., Soni V., Drozda K., Nutescu E.A., Cavallari L.H.;
"Warfarin dose requirements in a patient with the CYP2C9*14 allele.";
Pharmacogenomics 15:909-914(2014).
[30]
VARIANT PHE-434, CHARACTERIZATION OF VARIANT PHE-434,
BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
PubMed=25994031; DOI=10.1124/dmd.115.063412;
Dai D.P., Wang S.H., Li C.B., Geng P.W., Cai J., Wang H., Hu G.X.,
Cai J.P.;
"Identification and Functional Assessment of a New CYP2C9 Allelic
Variant CYP2C9*59.";
Drug Metab. Dispos. 43:1246-1249(2015).
-!- FUNCTION: Cytochromes P450 are a group of heme-thiolate
monooxygenases. In liver microsomes, this enzyme is involved in an
NADPH-dependent electron transport pathway. It oxidizes a variety
of structurally unrelated compounds, including steroids, fatty
acids, and xenobiotics (PubMed:25994031). This enzyme contributes
to the wide pharmacokinetics variability of the metabolism of
drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and
losartan (PubMed:25994031). {ECO:0000269|PubMed:25994031}.
-!- CATALYTIC ACTIVITY:
Reaction=(4R)-limonene + O2 + reduced [NADPH--hemoprotein
reductase] = (1R,5S)-carveol + H(+) + H2O + oxidized [NADPH--
hemoprotein reductase]; Xref=Rhea:RHEA:18957, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15382,
ChEBI:CHEBI:15388, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
EC=1.14.14.53; Evidence={ECO:0000269|PubMed:11950794};
-!- CATALYTIC ACTIVITY:
Reaction=(4S)-limonene + O2 + reduced [NADPH--hemoprotein
reductase] = (1S,5R)-carveol + H(+) + H2O + oxidized [NADPH--
hemoprotein reductase]; Xref=Rhea:RHEA:17945, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15383,
ChEBI:CHEBI:15389, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
EC=1.14.14.51; Evidence={ECO:0000269|PubMed:11950794};
-!- CATALYTIC ACTIVITY:
Reaction=(4S)-limonene + O2 + reduced [NADPH--hemoprotein
reductase] = (4S)-perillyl alcohol + H(+) + H2O + oxidized
[NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:23432, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:10782,
ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
ChEBI:CHEBI:15383, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
EC=1.14.14.52; Evidence={ECO:0000269|PubMed:11950794};
-!- CATALYTIC ACTIVITY:
Reaction=cholesterol + O2 + reduced [NADPH--hemoprotein reductase]
= 25-hydroxycholesterol + H(+) + H2O + oxidized [NADPH--
hemoprotein reductase]; Xref=Rhea:RHEA:50256, Rhea:RHEA-
COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113,
ChEBI:CHEBI:42977, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
Evidence={ECO:0000269|PubMed:21576599};
-!- COFACTOR:
Name=heme; Xref=ChEBI:CHEBI:30413;
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=1.25 mM for S-mephenytoin {ECO:0000269|PubMed:3079764};
KM=46.24 uM for tolbutamide {ECO:0000269|PubMed:25994031};
KM=4.73 uM for diclofenac {ECO:0000269|PubMed:25994031};
KM=1.58 uM for losartan {ECO:0000269|PubMed:25994031};
Vmax=9.22 pmol/min/pmol enzyme with tolbutamide as substrate
{ECO:0000269|PubMed:25994031};
Vmax=17.16 pmol/min/pmol enzyme with diclofenac as substrate
{ECO:0000269|PubMed:25994031};
Vmax=210.30 pmol/min/pmol enzyme with losartan as substrate
{ECO:0000269|PubMed:25994031};
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
membrane protein. Microsome membrane
{ECO:0000269|PubMed:21576599}; Peripheral membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P11712-1; Sequence=Displayed;
Name=2;
IsoId=P11712-2; Sequence=VSP_055573, VSP_055574;
Note=No experimental confirmation available.;
-!- INDUCTION: By rifampicin.
-!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee;
Note=CYP2C9 alleles;
URL="http://www.cypalleles.ki.se/cyp2c9.htm";
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/cyp2c9/";
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EMBL; AY341248; AAP88931.1; -; Genomic_DNA.
EMBL; AY702706; AAT94065.1; -; Genomic_DNA.
EMBL; AK289420; BAF82109.1; -; mRNA.
EMBL; AL359672; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471066; EAW50019.1; -; Genomic_DNA.
EMBL; CH471066; EAW50020.1; -; Genomic_DNA.
EMBL; BC020754; AAH20754.1; -; mRNA.
EMBL; BC070317; AAH70317.1; -; mRNA.
EMBL; BC125054; AAI25055.1; -; mRNA.
EMBL; D00173; BAA00123.1; -; mRNA.
EMBL; M15331; AAA52157.1; -; mRNA.
EMBL; M21939; AAA52158.1; -; mRNA.
EMBL; M21940; AAA52159.1; -; mRNA.
EMBL; S46963; AAB23864.2; ALT_SEQ; mRNA.
CCDS; CCDS7437.1; -. [P11712-1]
PIR; B38462; B38462.
PIR; D28951; D28951.
RefSeq; NP_000762.2; NM_000771.3. [P11712-1]
RefSeq; XP_016871247.1; XM_017015758.1.
UniGene; Hs.282624; -.
UniGene; Hs.615469; -.
PDB; 1OG2; X-ray; 2.60 A; A/B=30-490.
PDB; 1OG5; X-ray; 2.55 A; A/B=30-490.
PDB; 1R9O; X-ray; 2.00 A; A=18-490.
PDB; 4NZ2; X-ray; 2.45 A; A/B=30-490.
PDB; 5A5I; X-ray; 2.00 A; A=23-489.
PDB; 5A5J; X-ray; 2.90 A; A=23-489.
PDB; 5K7K; X-ray; 2.30 A; A=23-489.
PDB; 5W0C; X-ray; 2.00 A; A=18-489.
PDB; 5X23; X-ray; 2.00 A; A=19-490.
PDB; 5X24; X-ray; 2.48 A; A=19-490.
PDB; 5XXI; X-ray; 2.30 A; A=28-489.
PDBsum; 1OG2; -.
PDBsum; 1OG5; -.
PDBsum; 1R9O; -.
PDBsum; 4NZ2; -.
PDBsum; 5A5I; -.
PDBsum; 5A5J; -.
PDBsum; 5K7K; -.
PDBsum; 5W0C; -.
PDBsum; 5X23; -.
PDBsum; 5X24; -.
PDBsum; 5XXI; -.
ProteinModelPortal; P11712; -.
SMR; P11712; -.
BioGrid; 107937; 14.
IntAct; P11712; 8.
STRING; 9606.ENSP00000260682; -.
BindingDB; P11712; -.
ChEMBL; CHEMBL3397; -.
DrugBank; DB02507; 4-Hydroxy-3-[(1s)-3-Oxo-1-Phenylbutyl]-2h-Chromen-2-One.
DrugBank; DB05812; Abiraterone.
DrugBank; DB06736; Aceclofenac.
DrugBank; DB01418; Acenocoumarol.
DrugBank; DB00316; Acetaminophen.
DrugBank; DB00945; Acetylsalicylic acid.
DrugBank; DB06594; Agomelatine.
DrugBank; DB00969; Alosetron.
DrugBank; DB00404; Alprazolam.
DrugBank; DB01424; Aminophenazone.
DrugBank; DB01118; Amiodarone.
DrugBank; DB00321; Amitriptyline.
DrugBank; DB00381; Amlodipine.
DrugBank; DB00613; Amodiaquine.
DrugBank; DB00701; Amprenavir.
DrugBank; DB01217; Anastrozole.
DrugBank; DB01435; Antipyrine.
DrugBank; DB06605; Apixaban.
DrugBank; DB00673; Aprepitant.
DrugBank; DB04557; Arachidonic Acid.
DrugBank; DB01274; Arformoterol.
DrugBank; DB06413; Armodafinil.
DrugBank; DB06697; Artemether.
DrugBank; DB01072; Atazanavir.
DrugBank; DB01076; Atorvastatin.
DrugBank; DB01117; Atovaquone.
DrugBank; DB00972; Azelastine.
DrugBank; DB00307; Bexarotene.
DrugBank; DB01128; Bicalutamide.
DrugBank; DB00188; Bortezomib.
DrugBank; DB00559; Bosentan.
DrugBank; DB00835; Brompheniramine.
DrugBank; DB00921; Buprenorphine.
DrugBank; DB01156; Bupropion.
DrugBank; DB08875; Cabozantinib.
DrugBank; DB00201; Caffeine.
DrugBank; DB00796; Candesartan.
DrugBank; DB01101; Capecitabine.
DrugBank; DB00564; Carbamazepine.
DrugBank; DB00748; Carbinoxamine.
DrugBank; DB01136; Carvedilol.
DrugBank; DB00482; Celecoxib.
DrugBank; DB09063; Ceritinib.
DrugBank; DB00439; Cerivastatin.
DrugBank; DB00446; Chloramphenicol.
DrugBank; DB00672; Chlorpropamide.
DrugBank; DB00169; Cholecalciferol.
DrugBank; DB00501; Cimetidine.
DrugBank; DB00568; Cinnarizine.
DrugBank; DB00604; Cisapride.
DrugBank; DB00515; Cisplatin.
DrugBank; DB04920; Clevidipine.
DrugBank; DB00758; Clopidogrel.
DrugBank; DB00257; Clotrimazole.
DrugBank; DB00363; Clozapine.
DrugBank; DB00907; Cocaine.
DrugBank; DB01394; Colchicine.
DrugBank; DB05219; Crisaborole.
DrugBank; DB01176; Cyclizine.
DrugBank; DB00531; Cyclophosphamide.
DrugBank; DB00091; Cyclosporine.
DrugBank; DB06292; Dapagliflozin.
DrugBank; DB00250; Dapsone.
DrugBank; DB00705; Delavirdine.
DrugBank; DB00967; Desloratadine.
DrugBank; DB01234; Dexamethasone.
DrugBank; DB01191; Dexfenfluramine.
DrugBank; DB04856; Dexloxiglumide.
DrugBank; DB00514; Dextromethorphan.
DrugBank; DB00647; Dextropropoxyphene.
DrugBank; DB00829; Diazepam.
DrugBank; DB00586; Diclofenac.
DrugBank; DB01144; Diclofenamide.
DrugBank; DB00266; Dicoumarol.
DrugBank; DB00255; Diethylstilbestrol.
DrugBank; DB00343; Diltiazem.
DrugBank; DB01075; Diphenhydramine.
DrugBank; DB00822; Disulfiram.
DrugBank; DB00757; Dolasetron.
DrugBank; DB00843; Donepezil.
DrugBank; DB00988; Dopamine.
DrugBank; DB00869; Dorzolamide.
DrugBank; DB01142; Doxepin.
DrugBank; DB00470; Dronabinol.
DrugBank; DB00625; Efavirenz.
DrugBank; DB00216; Eletriptan.
DrugBank; DB08899; Enzalutamide.
DrugBank; DB00668; Epinephrine.
DrugBank; DB01240; Epoprostenol.
DrugBank; DB00876; Eprosartan.
DrugBank; DB00783; Estradiol.
DrugBank; DB00655; Estrone.
DrugBank; DB04574; Estrone sulfate.
DrugBank; DB00402; Eszopiclone.
DrugBank; DB00898; Ethanol.
DrugBank; DB00749; Etodolac.
DrugBank; DB01628; Etoricoxib.
DrugBank; DB06414; Etravirine.
DrugBank; DB01023; Felodipine.
DrugBank; DB01039; Fenofibrate.
DrugBank; DB01195; Flecainide.
DrugBank; DB00322; Floxuridine.
DrugBank; DB00196; Fluconazole.
DrugBank; DB04841; Flunarizine.
DrugBank; DB01544; Flunitrazepam.
DrugBank; DB00544; Fluorouracil.
DrugBank; DB00472; Fluoxetine.
DrugBank; DB00712; Flurbiprofen.
DrugBank; DB01095; Fluvastatin.
DrugBank; DB00176; Fluvoxamine.
DrugBank; DB00983; Formoterol.
DrugBank; DB01320; Fosphenytoin.
DrugBank; DB06741; Gavestinel.
DrugBank; DB00317; Gefitinib.
DrugBank; DB01241; Gemfibrozil.
DrugBank; DB01381; Ginkgo biloba.
DrugBank; DB01120; Gliclazide.
DrugBank; DB00222; Glimepiride.
DrugBank; DB01067; Glipizide.
DrugBank; DB01016; Glyburide.
DrugBank; DB01018; Guanfacine.
DrugBank; DB00502; Haloperidol.
DrugBank; DB01159; Halothane.
DrugBank; DB03317; Heme C.
DrugBank; DB01355; Hexobarbital.
DrugBank; DB05381; Histamine.
DrugBank; DB00062; Human Serum Albumin.
DrugBank; DB00327; Hydromorphone.
DrugBank; DB01050; Ibuprofen.
DrugBank; DB01177; Idarubicin.
DrugBank; DB01181; Ifosfamide.
DrugBank; DB00619; Imatinib.
DrugBank; DB00224; Indinavir.
DrugBank; DB00328; Indomethacin.
DrugBank; DB01029; Irbesartan.
DrugBank; DB00951; Isoniazid.
DrugBank; DB09570; Ixazomib.
DrugBank; DB01221; Ketamine.
DrugBank; DB06738; Ketobemidone.
DrugBank; DB01026; Ketoconazole.
DrugBank; DB01009; Ketoprofen.
DrugBank; DB00448; Lansoprazole.
DrugBank; DB01097; Leflunomide.
DrugBank; DB11560; Lesinurad.
DrugBank; DB04725; Licofelone.
DrugBank; DB00281; Lidocaine.
DrugBank; DB01601; Lopinavir.
DrugBank; DB00455; Loratadine.
DrugBank; DB06725; Lornoxicam.
DrugBank; DB00678; Losartan.
DrugBank; DB00227; Lovastatin.
DrugBank; DB09280; Lumacaftor.
DrugBank; DB01283; Lumiracoxib.
DrugBank; DB00603; Medroxyprogesterone acetate.
DrugBank; DB00784; Mefenamic acid.
DrugBank; DB01065; Melatonin.
DrugBank; DB00814; Meloxicam.
DrugBank; DB00532; Mephenytoin.
DrugBank; DB01357; Mestranol.
DrugBank; DB00333; Methadone.
DrugBank; DB00703; Methazolamide.
DrugBank; DB00763; Methimazole.
DrugBank; DB01028; Methoxyflurane.
DrugBank; DB00916; Metronidazole.
DrugBank; DB01110; Miconazole.
DrugBank; DB00370; Mirtazapine.
DrugBank; DB01171; Moclobemide.
DrugBank; DB00745; Modafinil.
DrugBank; DB00471; Montelukast.
DrugBank; DB11605; Myrrh.
DrugBank; DB00788; Naproxen.
DrugBank; DB00731; Nateglinide.
DrugBank; DB00220; Nelfinavir.
DrugBank; DB09048; Netupitant.
DrugBank; DB00238; Nevirapine.
DrugBank; DB00622; Nicardipine.
DrugBank; DB06803; Niclosamide.
DrugBank; DB00184; Nicotine.
DrugBank; DB01115; Nifedipine.
DrugBank; DB04868; Nilotinib.
DrugBank; DB00665; Nilutamide.
DrugBank; DB06712; Nilvadipine.
DrugBank; DB00540; Nortriptyline.
DrugBank; DB00334; Olanzapine.
DrugBank; DB09080; Olodaterol.
DrugBank; DB00338; Omeprazole.
DrugBank; DB00904; Ondansetron.
DrugBank; DB04938; Ospemifene.
DrugBank; DB00991; Oxaprozin.
DrugBank; DB01229; Paclitaxel.
DrugBank; DB00213; Pantoprazole.
DrugBank; DB00617; Paramethadione.
DrugBank; DB08439; Parecoxib.
DrugBank; DB00715; Paroxetine.
DrugBank; DB00850; Perphenazine.
DrugBank; DB03783; Phenacetin.
DrugBank; DB01174; Phenobarbital.
DrugBank; DB00946; Phenprocoumon.
DrugBank; DB00191; Phentermine.
DrugBank; DB00812; Phenylbutazone.
DrugBank; DB00252; Phenytoin.
DrugBank; DB01132; Pioglitazone.
DrugBank; DB00554; Piroxicam.
DrugBank; DB08860; Pitavastatin.
DrugBank; DB01411; Pranlukast.
DrugBank; DB06209; Prasugrel.
DrugBank; DB00175; Pravastatin.
DrugBank; DB00794; Primidone.
DrugBank; DB01032; Probenecid.
DrugBank; DB00396; Progesterone.
DrugBank; DB01131; Proguanil.
DrugBank; DB00420; Promazine.
DrugBank; DB01069; Promethazine.
DrugBank; DB01182; Propafenone.
DrugBank; DB00818; Propofol.
DrugBank; DB09396; Propoxyphene napsylate.
DrugBank; DB00205; Pyrimethamine.
DrugBank; DB01589; Quazepam.
DrugBank; DB00908; Quinidine.
DrugBank; DB00468; Quinine.
DrugBank; DB01129; Rabeprazole.
DrugBank; DB08896; Regorafenib.
DrugBank; DB01045; Rifampicin.
DrugBank; DB01201; Rifapentine.
DrugBank; DB00503; Ritonavir.
DrugBank; DB00533; Rofecoxib.
DrugBank; DB00412; Rosiglitazone.
DrugBank; DB01098; Rosuvastatin.
DrugBank; DB01698; Rutin.
DrugBank; DB00936; Salicylic acid.
DrugBank; DB01232; Saquinavir.
DrugBank; DB00418; Secobarbital.
DrugBank; DB01037; Selegiline.
DrugBank; DB01104; Sertraline.
DrugBank; DB00203; Sildenafil.
DrugBank; DB00641; Simvastatin.
DrugBank; DB06268; Sitaxentan.
DrugBank; DB00398; Sorafenib.
DrugBank; DB06820; Sulconazole.
DrugBank; DB00359; Sulfadiazine.
DrugBank; DB06150; Sulfadimethoxine.
DrugBank; DB00576; Sulfamethizole.
DrugBank; DB01015; Sulfamethoxazole.
DrugBank; DB08798; Sulfamoxole.
DrugBank; DB00259; Sulfanilamide.
DrugBank; DB06729; Sulfaphenazole.
DrugBank; DB00891; Sulfapyridine.
DrugBank; DB01138; Sulfinpyrazone.
DrugBank; DB00263; Sulfisoxazole.
DrugBank; DB00870; Suprofen.
DrugBank; DB00675; Tamoxifen.
DrugBank; DB06204; Tapentadol.
DrugBank; DB01079; Tegaserod.
DrugBank; DB00231; Temazepam.
DrugBank; DB00444; Teniposide.
DrugBank; DB00469; Tenoxicam.
DrugBank; DB00857; Terbinafine.
DrugBank; DB00342; Terfenadine.
DrugBank; DB00624; Testosterone.
DrugBank; DB01041; Thalidomide.
DrugBank; DB00277; Theophylline.
DrugBank; DB01154; Thiamylal.
DrugBank; DB00679; Thioridazine.
DrugBank; DB08816; Ticagrelor.
DrugBank; DB00208; Ticlopidine.
DrugBank; DB04831; Ticrynafen.
DrugBank; DB01007; Tioconazole.
DrugBank; DB01124; Tolbutamide.
DrugBank; DB00323; Tolcapone.
DrugBank; DB01036; Tolterodine.
DrugBank; DB00214; Torasemide.
DrugBank; DB05109; Trabectedin.
DrugBank; DB00752; Tranylcypromine.
DrugBank; DB00374; Treprostinil.
DrugBank; DB00755; Tretinoin.
DrugBank; DB00897; Triazolam.
DrugBank; DB00347; Trimethadione.
DrugBank; DB00440; Trimethoprim.
DrugBank; DB00726; Trimipramine.
DrugBank; DB00197; Troglitazone.
DrugBank; DB01361; Troleandomycin.
DrugBank; DB00580; Valdecoxib.
DrugBank; DB00313; Valproic Acid.
DrugBank; DB00177; Valsartan.
DrugBank; DB00285; Venlafaxine.
DrugBank; DB00661; Verapamil.
DrugBank; DB08828; Vismodegib.
DrugBank; DB00582; Voriconazole.
DrugBank; DB09068; Vortioxetine.
DrugBank; DB00682; Warfarin.
DrugBank; DB04898; Ximelagatran.
DrugBank; DB00549; Zafirlukast.
DrugBank; DB00943; Zalcitabine.
DrugBank; DB06737; Zaltoprofen.
DrugBank; DB00495; Zidovudine.
DrugBank; DB00744; Zileuton.
DrugBank; DB00425; Zolpidem.
DrugBank; DB01198; Zopiclone.
GuidetoPHARMACOLOGY; 1326; -.
SwissLipids; SLP:000001203; -.
iPTMnet; P11712; -.
PhosphoSitePlus; P11712; -.
BioMuta; CYP2C9; -.
DMDM; 6686268; -.
EPD; P11712; -.
jPOST; P11712; -.
PaxDb; P11712; -.
PeptideAtlas; P11712; -.
PRIDE; P11712; -.
ProteomicsDB; 52801; -.
Ensembl; ENST00000260682; ENSP00000260682; ENSG00000138109. [P11712-1]
Ensembl; ENST00000461906; ENSP00000495649; ENSG00000138109. [P11712-2]
GeneID; 1559; -.
KEGG; hsa:1559; -.
CTD; 1559; -.
DisGeNET; 1559; -.
EuPathDB; HostDB:ENSG00000138109.9; -.
GeneCards; CYP2C9; -.
HGNC; HGNC:2623; CYP2C9.
HPA; CAB016123; -.
HPA; HPA015066; -.
MalaCards; CYP2C9; -.
MIM; 601130; gene.
neXtProt; NX_P11712; -.
OpenTargets; ENSG00000138109; -.
Orphanet; 413681; Oral antidiabetic drugs toxicity or dose selection.
Orphanet; 413674; Vitamin K antagonists toxicity or dose selection.
PharmGKB; PA126; -.
eggNOG; KOG0156; Eukaryota.
eggNOG; COG2124; LUCA.
GeneTree; ENSGT00940000163209; -.
HOGENOM; HOG000036992; -.
HOVERGEN; HBG061848; -.
InParanoid; P11712; -.
KO; K17719; -.
OMA; LHEMTKV; -.
OrthoDB; 681235at2759; -.
PhylomeDB; P11712; -.
TreeFam; TF352043; -.
BioCyc; MetaCyc:HS06458-MONOMER; -.
BRENDA; 1.14.99.38; 2681.
Reactome; R-HSA-211981; Xenobiotics.
Reactome; R-HSA-211999; CYP2E1 reactions.
Reactome; R-HSA-2142670; Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET).
Reactome; R-HSA-2142816; Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE).
Reactome; R-HSA-9027307; Biosynthesis of maresin-like SPMs.
SABIO-RK; P11712; -.
SIGNOR; P11712; -.
ChiTaRS; CYP2C9; human.
EvolutionaryTrace; P11712; -.
GeneWiki; CYP2C9; -.
GenomeRNAi; 1559; -.
PRO; PR:P11712; -.
Proteomes; UP000005640; Chromosome 10.
Bgee; ENSG00000138109; Expressed in 106 organ(s), highest expression level in liver.
ExpressionAtlas; P11712; baseline and differential.
Genevisible; P11712; HS.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell.
GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central.
GO; GO:0034875; F:caffeine oxidase activity; IDA:BHF-UCL.
GO; GO:0008144; F:drug binding; IDA:BHF-UCL.
GO; GO:0020037; F:heme binding; IBA:GO_Central.
GO; GO:0005506; F:iron ion binding; IEA:InterPro.
GO; GO:0004497; F:monooxygenase activity; IDA:BHF-UCL.
GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL.
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.
GO; GO:0008395; F:steroid hydroxylase activity; IMP:BHF-UCL.
GO; GO:0043603; P:cellular amide metabolic process; IDA:BHF-UCL.
GO; GO:0042737; P:drug catabolic process; IMP:BHF-UCL.
GO; GO:0017144; P:drug metabolic process; IDA:BHF-UCL.
GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central.
GO; GO:0042738; P:exogenous drug catabolic process; IDA:BHF-UCL.
GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome.
GO; GO:0032787; P:monocarboxylic acid metabolic process; IDA:BHF-UCL.
GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL.
GO; GO:0097267; P:omega-hydroxylase P450 pathway; TAS:Reactome.
GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
GO; GO:0055114; P:oxidation-reduction process; IDA:BHF-UCL.
GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL.
GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL.
GO; GO:0019627; P:urea metabolic process; IDA:BHF-UCL.
GO; GO:0006805; P:xenobiotic metabolic process; IBA:GO_Central.
Gene3D; 1.10.630.10; -; 1.
InterPro; IPR001128; Cyt_P450.
InterPro; IPR017972; Cyt_P450_CS.
InterPro; IPR002401; Cyt_P450_E_grp-I.
InterPro; IPR036396; Cyt_P450_sf.
Pfam; PF00067; p450; 1.
PRINTS; PR00463; EP450I.
PRINTS; PR00385; P450.
SUPFAM; SSF48264; SSF48264; 1.
PROSITE; PS00086; CYTOCHROME_P450; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome;
Direct protein sequencing; Endoplasmic reticulum; Heme; Iron;
Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase;
Oxidoreductase; Polymorphism; Reference proteome; Steroid metabolism;
Sterol metabolism.
CHAIN 1 490 Cytochrome P450 2C9.
/FTId=PRO_0000051700.
METAL 435 435 Iron (heme axial ligand).
VAR_SEQ 161 162 AS -> GG (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_055573.
VAR_SEQ 163 490 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_055574.
VARIANT 19 19 L -> I (in allele CYP2C9*7;
dbSNP:rs67807361).
/FTId=VAR_018862.
VARIANT 125 125 R -> H (in allele CYP2C9*35;
dbSNP:rs72558189).
{ECO:0000269|PubMed:24956244}.
/FTId=VAR_075286.
VARIANT 125 125 R -> L (in allele CYP2C9*14;
dbSNP:rs72558189).
{ECO:0000269|PubMed:21451434}.
/FTId=VAR_075287.
VARIANT 144 144 R -> C (in allele CYP2C9*2;
dbSNP:rs1799853).
{ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:2827463,
ECO:0000269|PubMed:3697070,
ECO:0000269|PubMed:8946475,
ECO:0000269|PubMed:9110362,
ECO:0000269|Ref.3}.
/FTId=VAR_008343.
VARIANT 150 150 R -> H (in allele CYP2C9*8;
dbSNP:rs7900194).
{ECO:0000269|PubMed:15469410,
ECO:0000269|Ref.3}.
/FTId=VAR_018863.
VARIANT 204 204 N -> H (in allele CYP2C9*57).
{ECO:0000269|PubMed:23582453}.
/FTId=VAR_075288.
VARIANT 251 251 H -> R (in allele CYP2C9*9;
dbSNP:rs2256871).
{ECO:0000269|PubMed:15469410,
ECO:0000269|Ref.3}.
/FTId=VAR_018864.
VARIANT 272 272 E -> G (in allele CYP2C9*10;
dbSNP:rs9332130). {ECO:0000269|Ref.3}.
/FTId=VAR_018865.
VARIANT 335 335 R -> W (in allele CYP2C9*11;
dbSNP:rs28371685).
{ECO:0000269|PubMed:11926893,
ECO:0000269|PubMed:15469410}.
/FTId=VAR_018866.
VARIANT 358 358 Y -> C (in dbSNP:rs1057909).
{ECO:0000269|PubMed:3032244,
ECO:0000269|PubMed:3196692,
ECO:0000269|PubMed:9110362}.
/FTId=VAR_008344.
VARIANT 359 359 I -> L (in allele CYP2C9*3; responsible
for the tolbutamide poor metabolizer
phenotype; dbSNP:rs1057910).
{ECO:0000269|PubMed:15469410,
ECO:0000269|PubMed:8946475,
ECO:0000269|PubMed:9110362,
ECO:0000269|Ref.3}.
/FTId=VAR_008345.
VARIANT 359 359 I -> T (in allele CYP2C9*4;
dbSNP:rs56165452).
{ECO:0000269|PubMed:10739176}.
/FTId=VAR_013515.
VARIANT 360 360 D -> E (in allele CYP2C9*5; increases the
K(m) value for substrates tested;
dbSNP:rs28371686).
{ECO:0000269|PubMed:11455026,
ECO:0000269|PubMed:15469410}.
/FTId=VAR_013516.
VARIANT 413 413 L -> P (in dbSNP:rs28371687).
{ECO:0000269|PubMed:15469410}.
/FTId=VAR_024717.
VARIANT 417 417 G -> D. {ECO:0000269|PubMed:3032244,
ECO:0000269|PubMed:3196692,
ECO:0000269|PubMed:9110362}.
/FTId=VAR_008346.
VARIANT 434 434 I -> F (in allele CYP2C9*59; produces
warfarin hypersensitivity; increases
affinity but highly decreases enzymatic
activity for tolbutamide; no effect on
affinity but decreases enzymatic activity
for diclofenac; decreases affinity and
highly decreases enzymatic activity for
losartan). {ECO:0000269|PubMed:25994031}.
/FTId=VAR_075289.
VARIANT 489 489 P -> S (in allele CYP2C9*12;
dbSNP:rs9332239). {ECO:0000269|Ref.3}.
/FTId=VAR_018867.
CONFLICT 4 4 L -> I (in Ref. 2; no nucleotide entry).
{ECO:0000305}.
CONFLICT 6 6 V -> S (in Ref. 2; no nucleotide entry).
{ECO:0000305}.
CONFLICT 14 14 L -> M (in Ref. 11; AAB23864).
{ECO:0000305}.
CONFLICT 175 175 C -> Y (in Ref. 1; no nucleotide entry).
{ECO:0000305}.
CONFLICT 239 239 F -> L (in Ref. 1; no nucleotide entry).
{ECO:0000305}.
STRAND 33 35 {ECO:0000244|PDB:1R9O}.
TURN 37 39 {ECO:0000244|PDB:5X23}.
HELIX 42 44 {ECO:0000244|PDB:5X23}.
HELIX 47 61 {ECO:0000244|PDB:1R9O}.
STRAND 63 71 {ECO:0000244|PDB:1R9O}.
STRAND 73 77 {ECO:0000244|PDB:1R9O}.
HELIX 80 87 {ECO:0000244|PDB:1R9O}.
TURN 88 94 {ECO:0000244|PDB:1R9O}.
STRAND 95 97 {ECO:0000244|PDB:5A5J}.
TURN 105 107 {ECO:0000244|PDB:1R9O}.
STRAND 111 114 {ECO:0000244|PDB:5A5I}.
HELIX 117 131 {ECO:0000244|PDB:1R9O}.
STRAND 134 136 {ECO:0000244|PDB:1R9O}.
STRAND 137 139 {ECO:0000244|PDB:5X23}.
HELIX 141 157 {ECO:0000244|PDB:1R9O}.
TURN 158 161 {ECO:0000244|PDB:1R9O}.
HELIX 167 183 {ECO:0000244|PDB:1R9O}.
HELIX 192 208 {ECO:0000244|PDB:1R9O}.
HELIX 211 214 {ECO:0000244|PDB:5X23}.
HELIX 216 218 {ECO:0000244|PDB:5X23}.
HELIX 222 224 {ECO:0000244|PDB:5W0C}.
TURN 227 229 {ECO:0000244|PDB:5A5J}.
HELIX 230 253 {ECO:0000244|PDB:1R9O}.
HELIX 263 274 {ECO:0000244|PDB:1R9O}.
STRAND 275 277 {ECO:0000244|PDB:5X23}.
HELIX 284 315 {ECO:0000244|PDB:1R9O}.
HELIX 317 330 {ECO:0000244|PDB:1R9O}.
STRAND 333 335 {ECO:0000244|PDB:1R9O}.
HELIX 339 344 {ECO:0000244|PDB:1R9O}.
HELIX 346 359 {ECO:0000244|PDB:1R9O}.
STRAND 374 376 {ECO:0000244|PDB:1R9O}.
STRAND 379 381 {ECO:0000244|PDB:1R9O}.
STRAND 386 389 {ECO:0000244|PDB:1R9O}.
HELIX 392 395 {ECO:0000244|PDB:1R9O}.
TURN 398 400 {ECO:0000244|PDB:1R9O}.
STRAND 401 403 {ECO:0000244|PDB:1R9O}.
HELIX 409 412 {ECO:0000244|PDB:1R9O}.
STRAND 415 417 {ECO:0000244|PDB:1OG5}.
HELIX 431 433 {ECO:0000244|PDB:1R9O}.
HELIX 438 455 {ECO:0000244|PDB:1R9O}.
STRAND 456 462 {ECO:0000244|PDB:1R9O}.
HELIX 464 466 {ECO:0000244|PDB:1R9O}.
STRAND 475 477 {ECO:0000244|PDB:1R9O}.
STRAND 485 489 {ECO:0000244|PDB:1R9O}.
SEQUENCE 490 AA; 55628 MW; 4FDFC395303A4E3E CRC64;
MDSLVVLVLC LSCLLLLSLW RQSSGRGKLP PGPTPLPVIG NILQIGIKDI SKSLTNLSKV
YGPVFTLYFG LKPIVVLHGY EAVKEALIDL GEEFSGRGIF PLAERANRGF GIVFSNGKKW
KEIRRFSLMT LRNFGMGKRS IEDRVQEEAR CLVEELRKTK ASPCDPTFIL GCAPCNVICS
IIFHKRFDYK DQQFLNLMEK LNENIKILSS PWIQICNNFS PIIDYFPGTH NKLLKNVAFM
KSYILEKVKE HQESMDMNNP QDFIDCFLMK MEKEKHNQPS EFTIESLENT AVDLFGAGTE
TTSTTLRYAL LLLLKHPEVT AKVQEEIERV IGRNRSPCMQ DRSHMPYTDA VVHEVQRYID
LLPTSLPHAV TCDIKFRNYL IPKGTTILIS LTSVLHDNKE FPNPEMFDPH HFLDEGGNFK
KSKYFMPFSA GKRICVGEAL AGMELFLFLT SILQNFNLKS LVDPKNLDTT PVVNGFASVP
PFYQLCFIPV


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Pathways :
WP677: Momilactone biosynthesis
WP1077: cytochrome P450
WP1194: cytochrome P450
WP1219: cytochrome P450
WP1274: cytochrome P450
WP1390: cytochrome P450
WP2316: PPAR signaling pathway
WP43: cytochrome P450
WP696: Benzo(a)pyrene metabolism
WP958: cytochrome P450
WP1665: Limonene and pinene degradation
WP1502: Mitochondrial biogenesis
WP2430: Quercetin metabolism
WP1021: Phase I, non P450
WP1140: Phase I, non P450
WP1213: Phase I, non P450
WP1255: Phase I, non P450
WP1291: Phase I, non P450
WP136: Phase I, non P450
WP1573: Phase I, non P450
WP1633: Bisphenol A degradation
WP791: Phase I, non P450
WP904: Phase I, non P450
WP1006: metapathway biotransformation
WP1124: metapathway biotransformation

Related Genes :
[CYP2C9 CYP2C10] Cytochrome P450 2C9 (EC 1.14.14.-) ((R)-limonene 6-monooxygenase) (EC 1.14.14.53) ((S)-limonene 6-monooxygenase) (EC 1.14.14.51) ((S)-limonene 7-monooxygenase) (EC 1.14.14.52) (CYPIIC9) (Cholesterol 25-hydroxylase) (EC 1.14.14.-) (Cytochrome P-450MP) (Cytochrome P450 MP-4) (Cytochrome P450 MP-8) (Cytochrome P450 PB-1) (S-mephenytoin 4-hydroxylase)
[CYP2C19] Cytochrome P450 2C19 (EC 1.14.14.-) ((R)-limonene 6-monooxygenase) (EC 1.14.14.53) ((S)-limonene 6-monooxygenase) (EC 1.14.14.51) ((S)-limonene 7-monooxygenase) (EC 1.14.14.52) (CYPIIC17) (CYPIIC19) (Cytochrome P450-11A) (Cytochrome P450-254C) (Fenbendazole monooxygenase (4'-hydroxylating)) (EC 1.14.14.75) (Mephenytoin 4-hydroxylase)
[CYP2C8] Cytochrome P450 2C8 (EC 1.14.14.1) (CYPIIC8) (Cytochrome P450 IIC2) (Cytochrome P450 MP-12) (Cytochrome P450 MP-20) (Cytochrome P450 form 1) (S-mephenytoin 4-hydroxylase)
[CYP3A4 CYP3A3] Cytochrome P450 3A4 (EC 1.14.14.-) (1,8-cineole 2-exo-monooxygenase) (EC 1.14.14.56) (Albendazole monooxygenase (sulfoxide-forming)) (EC 1.14.14.73) (Albendazole sulfoxidase) (CYPIIIA3) (CYPIIIA4) (Cholesterol 25-hydroxylase) (EC 1.14.14.-) (Cytochrome P450 3A3) (Cytochrome P450 HLp) (Cytochrome P450 NF-25) (Cytochrome P450-PCN1) (Nifedipine oxidase) (Quinine 3-monooxygenase) (EC 1.14.14.55) (Taurochenodeoxycholate 6-alpha-hydroxylase) (EC 1.14.14.-)
[CYP4F2] Phylloquinone omega-hydroxylase CYP4F2 (EC 1.14.14.78) (20-hydroxyeicosatetraenoic acid synthase) (20-HETE synthase) (EC 1.14.14.-) (Arachidonic acid omega-hydroxylase) (CYPIVF2) (Cytochrome P450 4F2) (Cytochrome P450-LTB-omega) (Leukotriene-B(4) 20-monooxygenase 1) (Leukotriene-B(4) omega-hydroxylase 1) (EC 1.14.14.94)
[CYP4F3 LTB4H] Docosahexaenoic acid omega-hydroxylase CYP4F3 (EC 1.14.14.79) (20-hydroxyeicosatetraenoic acid synthase) (20-HETE synthase) (EC 1.14.14.-) (CYPIVF3) (Cytochrome P450 4F3) (Cytochrome P450-LTB-omega) (Leukotriene-B(4) 20-monooxygenase 2) (Leukotriene-B(4) omega-hydroxylase 2) (EC 1.14.14.94)
[cyp102A1 cyp102 BG04_163] Bifunctional cytochrome P450/NADPH--P450 reductase (Cytochrome P450(BM-3)) (Cytochrome P450BM-3) (Fatty acid monooxygenase) (Flavocytochrome P450 BM3) [Includes: Cytochrome P450 102A1 (EC 1.14.14.1); NADPH--cytochrome P450 reductase (EC 1.6.2.4)]
[cypD cyp102A2 yetO yfnJ BSU07250] Bifunctional cytochrome P450/NADPH--P450 reductase 1 (CYP102A2) (Fatty acid hydroxylase CypD) (Flavocytochrome P450 102A2) [Includes: Cytochrome P450 102A2 (EC 1.14.14.1); NADPH--cytochrome P450 reductase (EC 1.6.2.4)]
[cypB cyp102A3 yrhJ BSU27160] Bifunctional cytochrome P450/NADPH--P450 reductase 2 (CYP102A3) (Fatty acid hydroxylase CypB) (Flavocytochrome P450 102A3) [Includes: Cytochrome P450 102A3 (EC 1.14.14.1); NADPH--cytochrome P450 reductase (EC 1.6.2.4)]
[CYP17A1 CYP17 S17AH] Steroid 17-alpha-hydroxylase/17,20 lyase (EC 1.14.14.19) (17-alpha-hydroxyprogesterone aldolase) (EC 1.14.14.32) (CYPXVII) (Cytochrome P450 17A1) (Cytochrome P450-C17) (Cytochrome P450c17) (Steroid 17-alpha-monooxygenase)
[CYP27A1 CYP27] Sterol 26-hydroxylase, mitochondrial (EC 1.14.15.15) (5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase) (Cytochrome P-450C27/25) (Cytochrome P450 27) (Sterol 27-hydroxylase) (Vitamin D(3) 25-hydroxylase)
[CYP1A2] Cytochrome P450 1A2 (EC 1.14.14.1) (CYPIA2) (Cholesterol 25-hydroxylase) (Cytochrome P(3)450) (Cytochrome P450 4) (Cytochrome P450-P3)
[CYP2A6 CYP2A3] Cytochrome P450 2A6 (EC 1.14.13.-) (1,4-cineole 2-exo-monooxygenase) (CYPIIA6) (Coumarin 7-hydroxylase) (Cytochrome P450 IIA3) (Cytochrome P450(I))
[CYP505] Bifunctional cytochrome P450/NADPH--P450 reductase (Cytochrome P450foxy) (Fatty acid omega-hydroxylase) (P450foxy) [Includes: Cytochrome P450 505 (EC 1.14.14.1); NADPH--cytochrome P450 reductase (EC 1.6.2.4)]
[Cyp27a1] Sterol 26-hydroxylase, mitochondrial (EC 1.14.15.15) (5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase) (Cytochrome P-450C27/25) (Cytochrome P450 27) (Sterol 27-hydroxylase) (Vitamin D(3) 25-hydroxylase)
[Cyp4f3 Cyp4f18] Leukotriene-B(4) omega-hydroxylase 2 (EC 1.14.14.94) (CYPIVF3) (Cytochrome P450 4F3) (Cytochrome P450-LTB-omega) (Leukotriene-B(4) 20-monooxygenase 2)
[Cyp27a1 Cyp27] Sterol 26-hydroxylase, mitochondrial (EC 1.14.15.15) (5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase) (Cytochrome P-450C27/25) (Cytochrome P450 27) (Sterol 27-hydroxylase) (Vitamin D(3) 25-hydroxylase)
[CYP2D6 CYP2DL1] Cytochrome P450 2D6 (EC 1.14.14.1) (CYPIID6) (Cholesterol 25-hydroxylase) (Cytochrome P450-DB1) (Debrisoquine 4-hydroxylase)
[pikC picK] Cytochrome P450 monooxygenase PikC (EC 1.14.15.33) (Cytochrome P450 monooxygenase PicK) (Narbomycin C-12 hydroxylase) (Pikromycin synthase CYP107L1)
[Cyp2d4 Cyp2d-18 Cyp2d-4 Cyp2d18] Cytochrome P450 2D4 (EC 1.14.14.1) (CYPIID18) (CYPIID4) (Cytochrome P450 2D-29) (Cytochrome P450 2D-35) (Cytochrome P450 2D18) (Cytochrome P450-CMF3) (Cytochrome P450-DB4) (Debrisoquine 4-hydroxylase)
[CYP27A1 CYP27] Sterol 26-hydroxylase, mitochondrial (EC 1.14.15.15) (5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase) (Cytochrome P-450C27/25) (Cytochrome P450 27) (Sterol 27-hydroxylase) (Vitamin D(3) 25-hydroxylase)
[CYP21A2 CYP21 CYP21B] Steroid 21-hydroxylase (EC 1.14.14.16) (21-OHase) (Cytochrome P-450c21) (Cytochrome P450 21) (Cytochrome P450 XXI) (Cytochrome P450-C21) (Cytochrome P450-C21B)
[CYP701A8 KO1 Os06g0569500 LOC_Os06g37300 OSJNBa0062E01.27] Ent-sandaracopimaradiene 3-hydroxylase (EC 1.14.14.70) (Cytochrome P450 701A8) (Ent-kaurene oxidase 4) (OsKO4) (Ent-kaurene oxidase-like 4) (OsKOL4) (OsKOS1) (Syn-pimaradiene 3-monooxygenase) (EC 1.14.14.68)
[Cyp2e1 Cyp2e Cyp2e-1] Cytochrome P450 2E1 (EC 1.14.13.-) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-J) (Cytochrome P450RLM6)
[Cyp2e1 Cyp2e Cyp2e-1] Cytochrome P450 2E1 (EC 1.14.13.-) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-ALC) (Cytochrome P450-J)
[CYP2B6] Cytochrome P450 2B6 (EC 1.14.13.-) (1,4-cineole 2-exo-monooxygenase) (CYPIIB6) (Cytochrome P450 IIB1)
[Cyp2a4 Cyp2a-4] Cytochrome P450 2A4 (EC 1.14.14.1) (CYPIIA4) (Cytochrome P450-15-alpha) (Cytochrome P450-IIA3.1) (Testosterone 15-alpha-hydroxylase)
[Cyp2d1 Cyp2d-1 Cyp2d9] Cytochrome P450 2D1 (EC 1.14.14.1) (CYPIID1) (Cytochrome P450-CMF1A) (Cytochrome P450-DB1) (Cytochrome P450-UT-7) (Debrisoquine 4-hydroxylase)
[Cyp1a2 Cyp1a-2] Cytochrome P450 1A2 (EC 1.14.14.1) (CYPIA2) (Cholesterol 25-hydroxylase) (Cytochrome P450-P2) (Cytochrome P450-P3)
[CYP11A1 CYP11A] Cholesterol side-chain cleavage enzyme, mitochondrial (EC 1.14.15.6) (CYPXIA1) (Cholesterol desmolase) (Cytochrome P450 11A1) (Cytochrome P450(scc))

Bibliography :