CYP3A4

CYP3A4 (Cytochrome P450 Family 3 Subfamily A Member 4) is a Protein Coding gene. Diseases associated with CYP3A4 include Acetaminophen Metabolism and Tacrolimus Dose Selection. Among its related pathways are Gefitinib Pathway, Pharmacokinetics and Metformin Pathway, Pharmacodynamics. Gene Ontology (GO) annotations related to this gene include enzyme binding and iron ion binding. An important paralog of this gene is CYP3A7.

Cytochrome P450 Family 3 Subfamily A Member 4

A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:20702771, PubMed:19965576, 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:2732228, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:21576599, PubMed:21490593).

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:14559847, PubMed:12865317).

Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:2732228, PubMed:15373842, PubMed:15764715, PubMed:22773874).

Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:2732228, PubMed:15373842, PubMed:15764715).

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 D3) (PubMed:29461981).

Aflatoxin metabolic process Source: Reactome
Alkaloid catabolic process Source: BHF-UCL
Androgen metabolic process Source: BHF-UCL
Cholesterol metabolic process Source: UniProtKB-UniPathway
Drug catabolic process Source: BHF-UCL
Drug metabolic process Source: BHF-UCL
Estrogen metabolic process Source: UniProtKB
Exogenous drug catabolic process Source: BHF-UCL
Heterocycle metabolic process Source: BHF-UCL
Lipid hydroxylation Source: BHF-UCL
Lipid metabolic process Source: ProtInc
Long-chain fatty acid biosynthetic process Source: Reactome
Monoterpenoid metabolic process Source: BHF-UCL
Oxidative demethylation Source: BHF-UCL
Retinoic acid metabolic process Source: UniProtKB
Retinol metabolic process Source: UniProtKB
Steroid catabolic process Source: BHF-UCL
Steroid metabolic process Source: BHF-UCL
Vitamin D catabolic process Source: UniProtKB
Vitamin D metabolic process Source: BHF-UCL
Xenobiotic metabolic process Source: Reactome

Endoplasmic reticulum membrane; Microsome membrane

Vitamin D-dependent rickets 3 (VDDR3):
An autosomal dominant disorder of vitamin D metabolism resulting in early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D.

Helical: 2-22

Polyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro).