lmmol · Proteins

Cytochrome P450 3A4

UniProt P08684 Organism Homo sapiens Gene CYP3A3, CYP3A4 EC 1.14.14.1, 1.14.14.56, 1.14.14.73, 1.14.14.55

Also known as: CYP3A3, CYP3A4

Function

A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids. 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. 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. Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone. Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones. 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. Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond. Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling. 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). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance. Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole. Hydroxylates antimalarial drug quinine. Acts as a 1,4-cineole 2-exo-monooxygenase. Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)).

Classification

Family (Pfam)
PF00067 p450
InterPro
Cyt_P450, Cyt_P450_CS, Cyt_P450_E_CYP3A, Cyt_P450_E_grp-II, Cyt_P450_sf, Cytochrome_P450_3A
Functional cluster
Cytochrome P450 & Heme Enzymes

Experimental structures · PDB · 119

A predicted model is available from AlphaFold.

Gene Ontology · 42

Disease associations

Drugs targeting this protein · 3

Neighborhood · nearest proteins

CYP3A3CYP3A21CYP3A12CYP3A7CYP3A5CYP2C10CYP1A2
Nearest neighbours of Cytochrome P450 3A4: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 45 cited papers

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