UniProt functional annotation for P10632



	UniProt functional annotation for P10632

UniProt code: P10632.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316). {ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15766564, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:26427316, ECO:0000269|PubMed:7574697}.

Catalytic activity: Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1; Evidence={ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:14559847}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; Evidence={ECO:0000305|PubMed:11093772};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131970; Evidence={ECO:0000269|PubMed:7574697, ECO:0000305|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881; Evidence={ECO:0000305|PubMed:7574697};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131969; Evidence={ECO:0000269|PubMed:7574697, ECO:0000305|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877; Evidence={ECO:0000305|PubMed:7574697};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131965; Evidence={ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:7574697}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; Evidence={ECO:0000305|PubMed:19965576, ECO:0000305|PubMed:7574697};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131964; Evidence={ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:7574697}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000305|PubMed:19965576};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z,17Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52172, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:136441; Evidence={ECO:0000269|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52173; Evidence={ECO:0000305|PubMed:15766564};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z,17Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52176, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:136443; Evidence={ECO:0000269|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52177; Evidence={ECO:0000305|PubMed:15766564};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76634; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; Evidence={ECO:0000305|PubMed:19965576};

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39783, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76635; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39784; Evidence={ECO:0000305|PubMed:19965576};

Catalytic activity: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)- docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:136410; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; Evidence={ECO:0000305|PubMed:19965576};

Catalytic activity: Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)- docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52124, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:136411; Evidence={ECO:0000269|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52125; Evidence={ECO:0000305|PubMed:19965576};

Catalytic activity: Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-4-hydroxyretinoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51984, Rhea:RHEA- COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134178; Evidence={ECO:0000269|PubMed:11093772}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985; Evidence={ECO:0000305|PubMed:11093772};

Catalytic activity: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha,17beta-estriol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47332, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:27974, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:14559847}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47333; Evidence={ECO:0000305|PubMed:14559847};

Catalytic activity: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47204, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:14559847}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47205; Evidence={ECO:0000305|PubMed:14559847};

Cofactor: Name=heme; Xref=ChEBI:CHEBI:30413;

Biophysicochemical properties: Kinetic parameters: KM=50 uM for all-trans-retinoate (4-hydroxylation) {ECO:0000269|PubMed:11093772}; KM=5.4 uM for (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate (epoxygenation) {ECO:0000269|PubMed:15766564}; KM=6 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (epoxygenation) {ECO:0000269|PubMed:15766564}; KM=7.18 uM for paclitaxel {ECO:0000269|PubMed:26427316}; KM=1.35 uM for amodiaquine {ECO:0000269|PubMed:26427316}; Vmax=1211 pmol/min/nmol enzyme toward all-trans-retinoate (4- hydroxylation) {ECO:0000269|PubMed:11093772}; Vmax=6.2 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z,17Z)- eicosapentaenoate (epoxygenation) {ECO:0000269|PubMed:15766564}; Vmax=4.6 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z)- eicosatetraenoate (epoxygenation) {ECO:0000269|PubMed:15766564}; Vmax=2.18 pmol/min/pmol enzyme toward paclitaxel {ECO:0000269|PubMed:26427316}; Vmax=11.30 pmol/min/pmol enzyme toward amodiaquine {ECO:0000269|PubMed:26427316};

Pathway: Steroid metabolism. {ECO:0000269|PubMed:14559847}.

Pathway: Lipid metabolism; arachidonate metabolism. {ECO:0000269|PubMed:15766564, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:7574697}.

Pathway: Cofactor metabolism; retinol metabolism. {ECO:0000269|PubMed:11093772}.

Subcellular location: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Induction: By phenobarbital.

Polymorphism: Several alleles are found in the human population, contributing to interindividual variations in the therapeutic efficacy and toxicity of a myriad of drugs such as paclitaxel or amodiaquine. The allele shown here is CYP2C8*1 (PubMed:26427316). CYP2C8 genetic variations are associated with altered drug metabolism and adverse drug effects including acute rhabdomyolysis after cerivastatin use [MIM:618018]. {ECO:0000269|PubMed:15365880, ECO:0000269|PubMed:26427316}.

Similarity: Belongs to the cytochrome P450 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316). {ECO:0000269\|PubMed:11093772, ECO:0000269\|PubMed:14559847, ECO:0000269\|PubMed:15766564, ECO:0000269\|PubMed:19965576, ECO:0000269\|PubMed:26427316, ECO:0000269\|PubMed:7574697}.


Catalytic activity:		Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:142491; EC=1.14.14.1; Evidence={ECO:0000269\|PubMed:11093772, ECO:0000269\|PubMed:14559847}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17150; Evidence={ECO:0000305\|PubMed:11093772};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131970; Evidence={ECO:0000269\|PubMed:7574697, ECO:0000305\|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881; Evidence={ECO:0000305\|PubMed:7574697};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49876, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131969; Evidence={ECO:0000269\|PubMed:7574697, ECO:0000305\|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49877; Evidence={ECO:0000305\|PubMed:7574697};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49860, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131965; Evidence={ECO:0000269\|PubMed:19965576, ECO:0000269\|PubMed:7574697}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49861; Evidence={ECO:0000305\|PubMed:19965576, ECO:0000305\|PubMed:7574697};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:131964; Evidence={ECO:0000269\|PubMed:19965576, ECO:0000269\|PubMed:7574697}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000305\|PubMed:19965576};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z,17Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52172, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:136441; Evidence={ECO:0000269\|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52173; Evidence={ECO:0000305\|PubMed:15766564};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z,17Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52176, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:136443; Evidence={ECO:0000269\|PubMed:15766564}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52177; Evidence={ECO:0000305\|PubMed:15766564};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39779, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76634; Evidence={ECO:0000269\|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39780; Evidence={ECO:0000305\|PubMed:19965576};
Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)- eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:39783, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562, ChEBI:CHEBI:76635; Evidence={ECO:0000269\|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39784; Evidence={ECO:0000305\|PubMed:19965576};
Catalytic activity:		Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)- docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:136410; Evidence={ECO:0000269\|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121; Evidence={ECO:0000305\|PubMed:19965576};
Catalytic activity:		Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)- docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:52124, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016, ChEBI:CHEBI:136411; Evidence={ECO:0000269\|PubMed:19965576}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52125; Evidence={ECO:0000305\|PubMed:19965576};
Catalytic activity:		Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-4-hydroxyretinoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51984, Rhea:RHEA- COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134178; Evidence={ECO:0000269\|PubMed:11093772}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985; Evidence={ECO:0000305\|PubMed:11093772};
Catalytic activity:		Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha,17beta-estriol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47332, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:27974, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269\|PubMed:14559847}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47333; Evidence={ECO:0000305\|PubMed:14559847};
Catalytic activity:		Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47204, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:776, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269\|PubMed:14559847}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47205; Evidence={ECO:0000305\|PubMed:14559847};
Cofactor:		Name=heme; Xref=ChEBI:CHEBI:30413;
Biophysicochemical properties:		Kinetic parameters: KM=50 uM for all-trans-retinoate (4-hydroxylation) {ECO:0000269\|PubMed:11093772}; KM=5.4 uM for (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate (epoxygenation) {ECO:0000269\|PubMed:15766564}; KM=6 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (epoxygenation) {ECO:0000269\|PubMed:15766564}; KM=7.18 uM for paclitaxel {ECO:0000269\|PubMed:26427316}; KM=1.35 uM for amodiaquine {ECO:0000269\|PubMed:26427316}; Vmax=1211 pmol/min/nmol enzyme toward all-trans-retinoate (4- hydroxylation) {ECO:0000269\|PubMed:11093772}; Vmax=6.2 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z,17Z)- eicosapentaenoate (epoxygenation) {ECO:0000269\|PubMed:15766564}; Vmax=4.6 nmol/min/nmol enzyme toward (5Z,8Z,11Z,14Z)- eicosatetraenoate (epoxygenation) {ECO:0000269\|PubMed:15766564}; Vmax=2.18 pmol/min/pmol enzyme toward paclitaxel {ECO:0000269\|PubMed:26427316}; Vmax=11.30 pmol/min/pmol enzyme toward amodiaquine {ECO:0000269\|PubMed:26427316};
Pathway:		Steroid metabolism. {ECO:0000269\|PubMed:14559847}.
Pathway:		Lipid metabolism; arachidonate metabolism. {ECO:0000269\|PubMed:15766564, ECO:0000269\|PubMed:19965576, ECO:0000269\|PubMed:7574697}.
Pathway:		Cofactor metabolism; retinol metabolism. {ECO:0000269\|PubMed:11093772}.
Subcellular location:		Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Induction:		By phenobarbital.
Polymorphism:		Several alleles are found in the human population, contributing to interindividual variations in the therapeutic efficacy and toxicity of a myriad of drugs such as paclitaxel or amodiaquine. The allele shown here is CYP2C8*1 (PubMed:26427316). CYP2C8 genetic variations are associated with altered drug metabolism and adverse drug effects including acute rhabdomyolysis after cerivastatin use [MIM:618018]. {ECO:0000269\|PubMed:15365880, ECO:0000269\|PubMed:26427316}.
Similarity:		Belongs to the cytochrome P450 family. {ECO:0000305}.