LMPD Database

LMP002675

UniProt Annotations

Entry Information
Gene Namecytochrome P450, family 3, subfamily A, polypeptide 4
Protein EntryCP3A4_HUMAN
UniProt IDP08684
SpeciesHuman
Comments
Comment typeDescription
Catalytic Activity1,8-cineole + NADPH + O(2) = 2-exo-hydroxy- 1,8-cineole + NADP(+) + H(2)O.
Catalytic ActivityAlbendazole + NADPH + O(2) = albendazole S- oxide + NADP(+) + H(2)O.
Catalytic ActivityLithocholate + NADPH + O(2) = hyodeoxycholate + NADP(+) + H(2)O.
Catalytic ActivityQuinine + NADPH + O(2) = 3-hydroxyquinine + NADP(+) + H(2)O.
Catalytic ActivityTaurochenodeoxycholate + NADPH + O(2) = taurohyocholate + NADP(+) + H(2)O.
CofactorName=heme; Xref=ChEBI
FunctionCytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2- exo-monooxygenase. The enzyme also hydroxylates etoposide.
InductionBy glucocorticoids. Also induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.
MiscellaneousChimeric transcripts, characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 exons, have been detected. All are possibly produced by trans- splicing. The chimeric transcripts exist in 3 different combinations: CYP3A43 exon 1 joined in frame to CYP3A4 exons 2-13, CYP3A43 exon 1 joined in frame to CYP3A4 exons 4-13 and CYP3A43 exon 1 joined in frame to CYP3A4 exon 7-13. The longest chimeric isoform (CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6- beta-hydroxylase activity, while a shorter isoform (CYP3A43 exon 1 joined to CYP3A4 exons 4-13) does not. All chimeric transcripts are expressed at very low levels in the liver (PubMed:11726664).
PtmPolyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro).
SimilarityBelongs to the cytochrome P450 family.
Subcellular LocationEndoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane; Single-pass membrane protein.
Tissue SpecificityExpressed in prostate and liver. According to some authors, it is not expressed in brain (PubMed:19094056). According to others, weak levels of expression are measured in some brain locations (PubMed:19359404 and PubMed:18545703). Also expressed in epithelium of the small intestine and large intestine, bile duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder, intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary (at protein level). {ECO
Web ResourceName=Cytochrome P450 Allele Nomenclature Committee; Note=CYP3A4 alleles; URL="http://www.cypalleles.ki.se/cyp3a4.htm";
Web ResourceName=Wikipedia; Note=CYP3A4 entry; URL="http://en.wikipedia.org/wiki/CYP3A4";