CYP3A4
entrez
1576
canonical
uniprot
P08684
canonical
ensembl
ENSG00000160868
resolver
ensp
ENSP00000498939
resolver
ensp
ENSP00000529259
resolver
enst
ENST00000651514
resolver
genesymbol
CYP3A4
resolver
genesymbol_syn
CYP3A3
resolver
hgnc
HGNC:2637
resolver
uniprot
P05184
resolver
uniprot
Q16757
resolver
uniprot
Q6GRK0
resolver
uniprot
Q9UK50
resolver
uniprot_entry
CP3A4_HUMAN
resolver
uniprot_entry
Q6GRK0_HUMAN
resolver
uniprot_sec
P05184
resolver
uniprot_sec
Q16757
resolver
uniprot_sec
Q9UK50
resolver
activity_regulation
ACTIVITY REGULATION: Activated by cytochrome b5. {ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847}.
uniprot
proteins
amino_acid_sequence
MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFDMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVNETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGGLLQPEKPVVLKVESRDGTVSGA
uniprot
proteins
disease_involvement
DISEASE: Vitamin D-dependent rickets 3 (VDDR3) [MIM:619073]: 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. {ECO:0000269|PubMed:29461981}. Note=The gene represented in this entry is involved in disease pathogenesis.
uniprot
proteins
ec_number
1.14.14.1
uniprot
proteins
ec_number
1.14.14.55
uniprot
proteins
ec_number
1.14.14.56
uniprot
proteins
ec_number
1.14.14.73
uniprot
proteins
function
FUNCTION: 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). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:10759686, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:11159812, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15373842, ECO:0000269|PubMed:15764715, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20702771, ECO:0000269|PubMed:21490593, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:22773874, ECO:0000269|PubMed:2732228, ECO:0000269|PubMed:29461981, ECO:0000269|PubMed:8968357, ECO:0000269|PubMed:9435160}.
uniprot
proteins
mass_dalton
57343
uniprot
proteins
pathway_participation
PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:12865317}.; PATHWAY: Cofactor metabolism; retinol metabolism. {ECO:0000269|PubMed:10681376}.; PATHWAY: Steroid metabolism; cholesterol metabolism. {ECO:0000269|PubMed:21576599}.; PATHWAY: Lipid metabolism; fatty acid metabolism. {ECO:0000269|PubMed:19965576}.
uniprot
proteins
post_translational_modification
PTM: Polyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro). {ECO:0000269|PubMed:19103148}.
uniprot
proteins
protein_family
Cytochrome P450 family
uniprot
proteins
pubmed
10322772
uniprot
proteins
pubmed
10668853
uniprot
proteins
pubmed
10681376
uniprot
proteins
pubmed
10759686
uniprot
proteins
pubmed
11093772
uniprot
proteins
pubmed
11159812
uniprot
proteins
pubmed
11181494
uniprot
proteins
pubmed
11266076
uniprot
proteins
pubmed
11470997
uniprot
proteins
pubmed
11555828
uniprot
proteins
pubmed
11695850
uniprot
proteins
pubmed
11714865
uniprot
proteins
pubmed
11726664
uniprot
proteins
pubmed
11875366
uniprot
proteins
pubmed
12865317
uniprot
proteins
pubmed
14559847
uniprot
proteins
pubmed
15256616
uniprot
proteins
pubmed
15258162
uniprot
proteins
pubmed
15373842
uniprot
proteins
pubmed
15469410
uniprot
proteins
pubmed
15764715
uniprot
proteins
pubmed
18545703
uniprot
proteins
pubmed
19094056
uniprot
proteins
pubmed
19103148
uniprot
proteins
pubmed
19359404
uniprot
proteins
pubmed
19965576
uniprot
proteins
pubmed
20702771
uniprot
proteins
pubmed
21490593
uniprot
proteins
pubmed
21576599
uniprot
proteins
pubmed
22773874
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2463251
uniprot
proteins
pubmed
2563251
uniprot
proteins
pubmed
26988023
uniprot
proteins
pubmed
2732228
uniprot
proteins
pubmed
29461981
uniprot
proteins
pubmed
3243766
uniprot
proteins
pubmed
3267210
uniprot
proteins
pubmed
3460094
uniprot
proteins
pubmed
3464943
uniprot
proteins
pubmed
3898085
uniprot
proteins
pubmed
7894497
uniprot
proteins
pubmed
8035341
uniprot
proteins
pubmed
8968357
uniprot
proteins
pubmed
9435160
uniprot
proteins
sequence_length
503
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane {ECO:0000269|PubMed:21576599}; Single-pass membrane protein.
uniprot
proteins
transmembrane_region
TRANSMEM 2..22; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins