UniProt functional annotation for P10635



	UniProt functional annotation for P10635

UniProt code: P10635.

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 fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). 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:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25- hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:16352597, ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20972997, ECO:0000269|PubMed:21289075, ECO:0000269|PubMed:21576599}.

Catalytic activity: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49884, 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:131975; Evidence={ECO:0000269|PubMed:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885; Evidence={ECO:0000305|PubMed:20972997};

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:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881; Evidence={ECO:0000305|PubMed:20972997};

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:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000305|PubMed:20972997};

Catalytic activity: Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(8,9-epoxy- 5Z,11Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH-- hemoprotein reductase]; Xref=Rhea:RHEA:53140, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136989; Evidence={ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53141; Evidence={ECO:0000305|PubMed:21289075};

Catalytic activity: Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(11,12-epoxy- 5Z,8Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53144, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136990; Evidence={ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53145; Evidence={ECO:0000305|PubMed:21289075};

Catalytic activity: Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(14,15-epoxy- 5Z,8Z,11Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53148, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136991; Evidence={ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53149; Evidence={ECO:0000305|PubMed:21289075};

Catalytic activity: Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(20-hydroxy- 5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + oxidized [NADPH-- hemoprotein reductase]; Xref=Rhea:RHEA:53152, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136992; Evidence={ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53153; Evidence={ECO:0000305|PubMed:21289075};

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=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}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50257; Evidence={ECO:0000305|PubMed:21576599};

Catalytic activity: Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized [NADPH-- hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:10681376}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093; Evidence={ECO:0000305|PubMed:10681376};

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

Biophysicochemical properties: Kinetic parameters: KM=67 uM for all-trans retinol {ECO:0000269|PubMed:10681376}; KM=1.3 uM for anandamide (oxidation to 20-HETE) {ECO:0000269|PubMed:18698000}; KM=2.1 uM for anandamide (oxidation to 8,9-EpETrE-EA) {ECO:0000269|PubMed:18698000}; KM=2.6 uM for anandamide (oxidation to 11,12-EpETrE-EA) {ECO:0000269|PubMed:18698000}; KM=2.8 uM for anandamide (oxidation to 14,15-EpETrE-EA) {ECO:0000269|PubMed:18698000}; Vmax=193 pmol/min/nmol enzyme toward all-trans retinol {ECO:0000269|PubMed:10681376}; Vmax=3.7 pmol/min/nmol enzyme toward anandamide (oxidation to 20- HETE) {ECO:0000269|PubMed:18698000}; Vmax=1.6 pmol/min/nmol enzyme toward anandamide (oxidation to 8,9- EpETrE-EA) {ECO:0000269|PubMed:18698000}; Vmax=1.1 pmol/min/nmol enzyme toward anandamide (oxidation to 11,12- EpETrE-EA) {ECO:0000269|PubMed:18698000}; Vmax=1.3 pmol/min/nmol enzyme toward anandamide (oxidation to 14,15- EpETrE-EA) {ECO:0000269|PubMed:18698000};

Pathway: Cofactor metabolism; retinol metabolism. {ECO:0000269|PubMed:10681376}.

Pathway: Lipid metabolism; fatty acid metabolism. {ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20972997}.

Pathway: Steroid metabolism; cholesterol metabolism. {ECO:0000269|PubMed:21576599}.

Subcellular location: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane {ECO:0000269|PubMed:21576599}; Peripheral membrane protein.

Induction: By pregnancy.

Polymorphism: Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and numerous other drugs. Different alleles are known, including CYP2D6*1 (PubMed:15768052), CYP2D6*2 (PubMed:25469868), CYP2D6*6B/6C (PubMed:7868129), CYP2D6*7 also known CYP2D6E (PubMed:7845481), CYP2D6*9 also known CYP2D6C (PubMed:1844820), CYP2D6*10 also known CYP2D6J (PubMed:8287064, PubMed:25469868), CYP2D6*12 (PubMed:8655150), CYP2D6*14 (PubMed:10064570), CYP2D6*17 also known CYP2D6Z (PubMed:8971426), CYP2D6*41B (PubMed:15768052), CYP2D6*45A (PubMed:15768052), CYP2D6*45B (PubMed:15768052), CYP2D6*46 (PubMed:15768052), CYP2D6*87 (PubMed:25469868), CYP2D6*88 (PubMed:25469868), CYP2D6*89 (PubMed:25469868), CYP2D6*90 (PubMed:25469868), CYP2D6*91 (PubMed:25469868), CYP2D6*93 (PubMed:25469868), C CYP2D6*94 (PubMed:25469868), CYP2D6*97 (PubMed:25469868) and CYP2D6*98 (PubMed:25469868). Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are functional (PubMed:15768052). The sequence shown is that of isozyme CYP2D6.1 corresponding to allele CYP2D6*1. {ECO:0000269|PubMed:10064570, ECO:0000269|PubMed:15768052, ECO:0000269|PubMed:16352597, ECO:0000269|PubMed:1844820, ECO:0000269|PubMed:25469868, ECO:0000269|PubMed:7845481, ECO:0000269|PubMed:7868129, ECO:0000269|PubMed:8655150, ECO:0000269|PubMed:8971426}.

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 fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). 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:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25- hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. {ECO:0000269\|PubMed:10681376, ECO:0000269\|PubMed:16352597, ECO:0000269\|PubMed:18698000, ECO:0000269\|PubMed:19965576, ECO:0000269\|PubMed:20972997, ECO:0000269\|PubMed:21289075, ECO:0000269\|PubMed:21576599}.


Catalytic activity:		Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH-- hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49884, 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:131975; Evidence={ECO:0000269\|PubMed:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885; Evidence={ECO:0000305\|PubMed:20972997};
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:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881; Evidence={ECO:0000305\|PubMed:20972997};
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:20972997}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857; Evidence={ECO:0000305\|PubMed:20972997};
Catalytic activity:		Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(8,9-epoxy- 5Z,11Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH-- hemoprotein reductase]; Xref=Rhea:RHEA:53140, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136989; Evidence={ECO:0000269\|PubMed:18698000, ECO:0000269\|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53141; Evidence={ECO:0000305\|PubMed:21289075};
Catalytic activity:		Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(11,12-epoxy- 5Z,8Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53144, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136990; Evidence={ECO:0000269\|PubMed:18698000, ECO:0000269\|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53145; Evidence={ECO:0000305\|PubMed:21289075};
Catalytic activity:		Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(14,15-epoxy- 5Z,8Z,11Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53148, Rhea:RHEA-COMP:11964, Rhea:RHEA- COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136991; Evidence={ECO:0000269\|PubMed:18698000, ECO:0000269\|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53149; Evidence={ECO:0000305\|PubMed:21289075};
Catalytic activity:		Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(20-hydroxy- 5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + oxidized [NADPH-- hemoprotein reductase]; Xref=Rhea:RHEA:53152, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136992; Evidence={ECO:0000269\|PubMed:18698000, ECO:0000269\|PubMed:21289075}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53153; Evidence={ECO:0000305\|PubMed:21289075};
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=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}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50257; Evidence={ECO:0000305\|PubMed:21576599};
Catalytic activity:		Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized [NADPH-- hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269\|PubMed:10681376}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093; Evidence={ECO:0000305\|PubMed:10681376};
Cofactor:		Name=heme; Xref=ChEBI:CHEBI:30413;
Biophysicochemical properties:		Kinetic parameters: KM=67 uM for all-trans retinol {ECO:0000269\|PubMed:10681376}; KM=1.3 uM for anandamide (oxidation to 20-HETE) {ECO:0000269\|PubMed:18698000}; KM=2.1 uM for anandamide (oxidation to 8,9-EpETrE-EA) {ECO:0000269\|PubMed:18698000}; KM=2.6 uM for anandamide (oxidation to 11,12-EpETrE-EA) {ECO:0000269\|PubMed:18698000}; KM=2.8 uM for anandamide (oxidation to 14,15-EpETrE-EA) {ECO:0000269\|PubMed:18698000}; Vmax=193 pmol/min/nmol enzyme toward all-trans retinol {ECO:0000269\|PubMed:10681376}; Vmax=3.7 pmol/min/nmol enzyme toward anandamide (oxidation to 20- HETE) {ECO:0000269\|PubMed:18698000}; Vmax=1.6 pmol/min/nmol enzyme toward anandamide (oxidation to 8,9- EpETrE-EA) {ECO:0000269\|PubMed:18698000}; Vmax=1.1 pmol/min/nmol enzyme toward anandamide (oxidation to 11,12- EpETrE-EA) {ECO:0000269\|PubMed:18698000}; Vmax=1.3 pmol/min/nmol enzyme toward anandamide (oxidation to 14,15- EpETrE-EA) {ECO:0000269\|PubMed:18698000};
Pathway:		Cofactor metabolism; retinol metabolism. {ECO:0000269\|PubMed:10681376}.
Pathway:		Lipid metabolism; fatty acid metabolism. {ECO:0000269\|PubMed:19965576, ECO:0000269\|PubMed:20972997}.
Pathway:		Steroid metabolism; cholesterol metabolism. {ECO:0000269\|PubMed:21576599}.
Subcellular location:		Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane {ECO:0000269\|PubMed:21576599}; Peripheral membrane protein.
Induction:		By pregnancy.
Polymorphism:		Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and numerous other drugs. Different alleles are known, including CYP2D61 (PubMed:15768052), CYP2D62 (PubMed:25469868), CYP2D66B/6C (PubMed:7868129), CYP2D67 also known CYP2D6E (PubMed:7845481), CYP2D69 also known CYP2D6C (PubMed:1844820), CYP2D610 also known CYP2D6J (PubMed:8287064, PubMed:25469868), CYP2D612 (PubMed:8655150), CYP2D614 (PubMed:10064570), CYP2D617 also known CYP2D6Z (PubMed:8971426), CYP2D641B (PubMed:15768052), CYP2D645A (PubMed:15768052), CYP2D645B (PubMed:15768052), CYP2D646 (PubMed:15768052), CYP2D687 (PubMed:25469868), CYP2D688 (PubMed:25469868), CYP2D689 (PubMed:25469868), CYP2D690 (PubMed:25469868), CYP2D691 (PubMed:25469868), CYP2D693 (PubMed:25469868), C CYP2D694 (PubMed:25469868), CYP2D697 (PubMed:25469868) and CYP2D698 (PubMed:25469868). Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are functional (PubMed:15768052). The sequence shown is that of isozyme CYP2D6.1 corresponding to allele CYP2D6*1. {ECO:0000269\|PubMed:10064570, ECO:0000269\|PubMed:15768052, ECO:0000269\|PubMed:16352597, ECO:0000269\|PubMed:1844820, ECO:0000269\|PubMed:25469868, ECO:0000269\|PubMed:7845481, ECO:0000269\|PubMed:7868129, ECO:0000269\|PubMed:8655150, ECO:0000269\|PubMed:8971426}.
Similarity:		Belongs to the cytochrome P450 family. {ECO:0000305}.