{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P08684","secondaryAccessions":["P05184","Q16757","Q9UK50"],"uniProtkbId":"CP3A4_HUMAN","entryAudit":{"firstPublicDate":"1988-01-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-01-23","entryVersion":254,"sequenceVersion":4},"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":"15373842"}],"value":"Cytochrome P450 3A4"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11555828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12865317"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2732228"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9435160"}],"value":"1.14.14.1"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11695850"}],"value":"1,4-cineole 2-exo-monooxygenase"}},{"fullName":{"value":"1,8-cineole 2-exo-monooxygenase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11159812"}],"value":"1.14.14.56"}]},{"fullName":{"value":"Albendazole monooxygenase (sulfoxide-forming)"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10759686"}],"value":"1.14.14.73"}]},{"fullName":{"value":"Albendazole sulfoxidase"}},{"fullName":{"value":"CYPIIIA3"}},{"fullName":{"value":"CYPIIIA4"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"21576599"}],"value":"Cholesterol 25-hydroxylase"}},{"fullName":{"value":"Cytochrome P450 3A3"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"3460094"}],"value":"Cytochrome P450 HLp"}},{"fullName":{"value":"Cytochrome P450 NF-25"}},{"fullName":{"value":"Cytochrome P450-PCN1"}},{"fullName":{"value":"Nifedipine oxidase"}},{"fullName":{"value":"Quinine 3-monooxygenase"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8968357"}],"value":"1.14.14.55"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11470997"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:2637"}],"value":"CYP3A4"},"synonyms":[{"value":"CYP3A3"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10681376"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10759686"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11093772"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11159812"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11555828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11695850"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12865317"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14559847"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15373842"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15764715"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19965576"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20702771"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21490593"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21576599"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22773874"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2732228"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29461981"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8968357"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9435160"}],"value":"A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, 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). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"an organic molecule + reduced [NADPH--hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH--hemoprotein reductase] + H2O + 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All chimeric transcripts are expressed at very low levels in the liver (PubMed:11726664)"}],"commentType":"MISCELLANEOUS"},{"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/CYP3A4","ftp":false,"note":"CYP3A4 alleles"},{"commentType":"WEB RESOURCE","resourceName":"Wikipedia","resourceUrl":"https://en.wikipedia.org/wiki/CYP3A4","ftp":false,"note":"CYP3A4 entry"}],"features":[{"type":"Initiator 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