{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P10635","secondaryAccessions":["Q16752","Q2XND6","Q2XND7","Q2XNE0","Q6B012","Q6NXU8"],"uniProtkbId":"CP2D6_HUMAN","entryAudit":{"firstPublicDate":"1989-07-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2005-12-20","entryVersion":245,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"18698000"}],"value":"Cytochrome P450 2D6"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18698000"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21289075"}],"value":"1.14.14.-"}]},"alternativeNames":[{"fullName":{"value":"CYPIID6"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"21576599"}],"value":"Cholesterol 25-hydroxylase"}},{"fullName":{"value":"Cytochrome P450-DB1"}},{"fullName":{"value":"Debrisoquine 4-hydroxylase"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"21289075"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:2625"}],"value":"CYP2D6"},"synonyms":[{"value":"CYP2DL1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10681376"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16352597"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18698000"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19965576"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20972997"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21289075"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21576599"}],"value":"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"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH--hemoprotein reductase] + O2 = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + oxidized [NADPH--hemoprotein reductase] + H2O + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:49884"},{"database":"Rhea","id":"RHEA-COMP:11964"},{"database":"Rhea","id":"RHEA-COMP:11965"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:15379"},{"database":"ChEBI","id":"CHEBI:32395"},{"database":"ChEBI","id":"CHEBI:57618"},{"database":"ChEBI","id":"CHEBI:58210"},{"database":"ChEBI","id":"CHEBI:131975"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20972997"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:49885"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"20972997"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH--hemoprotein reductase] + O2 = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + oxidized [NADPH--hemoprotein reductase] + H2O + 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oxidized [NADPH--hemoprotein reductase] + H2O + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:53140"},{"database":"Rhea","id":"RHEA-COMP:11964"},{"database":"Rhea","id":"RHEA-COMP:11965"},{"database":"ChEBI","id":"CHEBI:2700"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:15379"},{"database":"ChEBI","id":"CHEBI:57618"},{"database":"ChEBI","id":"CHEBI:58210"},{"database":"ChEBI","id":"CHEBI:136989"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18698000"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21289075"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:53141"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"21289075"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + reduced [NADPH--hemoprotein reductase] + O2 = 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[NADPH--hemoprotein reductase] + H2O + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:39783"},{"database":"Rhea","id":"RHEA-COMP:11964"},{"database":"Rhea","id":"RHEA-COMP:11965"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:15379"},{"database":"ChEBI","id":"CHEBI:57618"},{"database":"ChEBI","id":"CHEBI:58210"},{"database":"ChEBI","id":"CHEBI:58562"},{"database":"ChEBI","id":"CHEBI:76635"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19965576"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:39784"},"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"19965576"}]}]},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH--hemoprotein reductase] + O2 = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + oxidized [NADPH--hemoprotein 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retinol","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10681376"}]},{"constant":1.3,"unit":"uM","substrate":"anandamide (oxidation to 20-HETE)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18698000"}]},{"constant":2.1,"unit":"uM","substrate":"anandamide (oxidation to 8,9-EpETrE-EA)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18698000"}]},{"constant":2.6,"unit":"uM","substrate":"anandamide (oxidation to 11,12-EpETrE-EA)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18698000"}]},{"constant":2.8,"unit":"uM","substrate":"anandamide (oxidation to 14,15-EpETrE-EA)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18698000"}]}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10681376"}],"value":"Cofactor metabolism; retinol metabolism"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19965576"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20972997"}],"value":"Lipid metabolism; fatty acid metabolism"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21576599"}],"value":"Steroid metabolism; cholesterol metabolism"}],"commentType":"PATHWAY"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"value":"Endoplasmic reticulum membrane","id":"SL-0097"},"topology":{"value":"Peripheral membrane protein","id":"SL-9903"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21576599"}],"value":"Microsome membrane","id":"SL-0165"},"topology":{"value":"Peripheral membrane protein","id":"SL-9903"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P10635-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P10635-2"],"sequenceIds":["VSP_044486"],"isoformSequenceStatus":"Described"}]},{"texts":[{"value":"By pregnancy"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10064570"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15768052"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16352597"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1844820"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25469868"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7845481"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7868129"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8655150"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8971426"}],"value":"Genetic variations in CYP2D6 are the cause of altered 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"}],"commentType":"POLYMORPHISM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the cytochrome P450 family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"PharmVar Pharmacogen Variation Consortium","resourceUrl":"https://www.pharmvar.org/gene/CYP2D6","ftp":false,"note":"CYP2D6 alleles"},{"commentType":"WEB RESOURCE","resourceName":"Wikipedia","resourceUrl":"https://en.wikipedia.org/wiki/CYP2D6","ftp":false,"note":"CYP2D6 entry"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":497,"modifier":"EXACT"}},"description":"Cytochrome P450 2D6","featureId":"PRO_0000051731"},{"type":"Binding site","location":{"start":{"value":301,"modifier":"EXACT"},"end":{"value":301,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000305"}],"ligand":{"name":"substrate"}},{"type":"Binding 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