Gene/Proteome Database (LMPD)
LMPD ID
LMP002675
Gene ID
Species
Homo sapiens (Human)
Gene Name
cytochrome P450, family 3, subfamily A, polypeptide 4
Gene Symbol
Synonyms
CP33; CP34; CYP3A; CYP3A3; CYPIIIA3; CYPIIIA4; HLP; NF-25; P450C3; P450PCN1
Alternate Names
cytochrome P450 3A4; nifedipine oxidase; cytochrome P450 3A3; cytochrome P450 HLp; cytochrome P450-PCN1; cytochrome P450 NF-25; albendazole sulfoxidase; quinine 3-monooxygenase; albendazole monooxygenase; P450-III, steroid inducible; glucocorticoid-inducible P450; 1,8-cineole 2-exo-monooxygenase; taurochenodeoxycholate 6-alpha-hydroxylase; cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 3; cytochrome P450, subfamily IIIA (niphedipine oxidase), polypeptide 4
Chromosome
7
Map Location
7q21.1
EC Number
1.14.13.-
Summary
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs in use today, including acetaminophen, codeine, cyclosporin A, diazepam and erythromycin. The enzyme also metabolizes some steroids and carcinogens. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Previously another CYP3A gene, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Feb 2011]
Orthologs
Proteins
| cytochrome P450 3A4 isoform 1 | |
|---|---|
| Refseq ID | NP_059488 |
| Protein GI | 13435386 |
| UniProt ID | P08684 |
| mRNA ID | NM_017460 |
| Length | 503 |
| RefSeq Status | REVIEWED |
| MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFDMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVNETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGGLLQPEKPVVLKVESRDGTVSGA | |
| cytochrome P450 3A4 isoform 2 | |
|---|---|
| Refseq ID | NP_001189784 |
| Protein GI | 322302351 |
| UniProt ID | P08684 |
| mRNA ID | NM_001202855 |
| Length | 502 |
| RefSeq Status | REVIEWED |
| MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFDMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSIIFPFLIPILEVLNICVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVNETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGGLLQPEKPVVLKVESRDGTVSGA | |
Gene Information
Entrez Gene ID
Gene Name
cytochrome P450, family 3, subfamily A, polypeptide 4
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | IDA:BHF-UCL | C | cytoplasm |
| GO:0005789 | TAS:Reactome | C | endoplasmic reticulum membrane |
| GO:0016021 | IEA:UniProtKB-KW | C | integral component of membrane |
| GO:0043231 | TAS:ProtInc | C | intracellular membrane-bounded organelle |
| GO:0047638 | IEA:UniProtKB-EC | F | albendazole monooxygenase activity |
| GO:0034875 | IDA:BHF-UCL | F | caffeine oxidase activity |
| GO:0019899 | IPI:BHF-UCL | F | enzyme binding |
| GO:0020037 | IEA:InterPro | F | heme binding |
| GO:0005506 | IDA:BHF-UCL | F | iron ion binding |
| GO:0004497 | ISS:UniProtKB | F | monooxygenase activity |
| GO:0016491 | IDA:BHF-UCL | F | oxidoreductase activity |
| GO:0016712 | IEA:InterPro | F | oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen |
| GO:0019825 | TAS:ProtInc | F | oxygen binding |
| GO:0050591 | IEA:UniProtKB-EC | F | quinine 3-monooxygenase activity |
| GO:0005496 | IDA:BHF-UCL | F | steroid binding |
| GO:0008395 | IMP:BHF-UCL | F | steroid hydroxylase activity |
| GO:0033780 | IEA:UniProtKB-EC | F | taurochenodeoxycholate 6alpha-hydroxylase activity |
| GO:0050649 | IMP:BHF-UCL | F | testosterone 6-beta-hydroxylase activity |
| GO:0070576 | IDA:BHF-UCL | F | vitamin D 24-hydroxylase activity |
| GO:0030343 | IDA:BHF-UCL | F | vitamin D3 25-hydroxylase activity |
| GO:0009822 | IDA:BHF-UCL | P | alkaloid catabolic process |
| GO:0008209 | TAS:BHF-UCL | P | androgen metabolic process |
| GO:0036378 | IDA:GOC | P | calcitriol biosynthetic process from calciol |
| GO:0042737 | IDA:BHF-UCL | P | drug catabolic process |
| GO:0017144 | IDA:BHF-UCL | P | drug metabolic process |
| GO:0042738 | IDA:BHF-UCL | P | exogenous drug catabolic process |
| GO:0046483 | IDA:BHF-UCL | P | heterocycle metabolic process |
| GO:0006629 | TAS:ProtInc | P | lipid metabolic process |
| GO:0016098 | IDA:BHF-UCL | P | monoterpenoid metabolic process |
| GO:0055114 | IDA:BHF-UCL | P | oxidation-reduction process |
| GO:0070989 | IDA:BHF-UCL | P | oxidative demethylation |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0006706 | IMP:BHF-UCL | P | steroid catabolic process |
| GO:0008202 | IMP:BHF-UCL | P | steroid metabolic process |
| GO:0042359 | IC:BHF-UCL | P | vitamin D metabolic process |
| GO:0006805 | TAS:Reactome | P | xenobiotic metabolic process |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa05204 | Chemical carcinogenesis |
Domain Information
UniProt Annotations
Entry Information
Gene Name
cytochrome P450, family 3, subfamily A, polypeptide 4
Protein Entry
CP3A4_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Catalytic Activity | 1,8-cineole + NADPH + O(2) = 2-exo-hydroxy- 1,8-cineole + NADP(+) + H(2)O. |
| Catalytic Activity | Albendazole + NADPH + O(2) = albendazole S- oxide + NADP(+) + H(2)O. |
| Catalytic Activity | Lithocholate + NADPH + O(2) = hyodeoxycholate + NADP(+) + H(2)O. |
| Catalytic Activity | Quinine + NADPH + O(2) = 3-hydroxyquinine + NADP(+) + H(2)O. |
| Catalytic Activity | Taurochenodeoxycholate + NADPH + O(2) = taurohyocholate + NADP(+) + H(2)O. |
| Cofactor | Name=heme; Xref=ChEBI |
| Function | Cytochromes 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. |
| Induction | By glucocorticoids. Also induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. |
| Miscellaneous | Chimeric 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). |
| Ptm | Polyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro). |
| Similarity | Belongs to the cytochrome P450 family. |
| Subcellular Location | Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane; Single-pass membrane protein. |
| Tissue Specificity | Expressed 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 Resource | Name=Cytochrome P450 Allele Nomenclature Committee; Note=CYP3A4 alleles; URL="http://www.cypalleles.ki.se/cyp3a4.htm"; |
| Web Resource | Name=Wikipedia; Note=CYP3A4 entry; URL="http://en.wikipedia.org/wiki/CYP3A4"; |
Identical and Related Proteins
Unique RefSeq proteins for LMP002675 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 13435386 | RefSeq | NP_059488 | 503 | cytochrome P450 3A4 isoform 1 |
| 322302351 | RefSeq | NP_001189784 | 502 | cytochrome P450 3A4 isoform 2 |
Identical Sequences to LMP002675 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:322302351 | GenBank | EAW76636.1 | 502 | cytochrome P450, family 3, subfamily A, polypeptide 4, isoform CRA_b [Homo sapiens] |
| GI:13435386 | GenBank | AFQ85871.1 | 503 | Sequence 20 from patent US 8252559 |
| GI:13435386 | GenBank | AGD01519.1 | 503 | Sequence 1042 from patent US 8338124 |
| GI:13435386 | GenBank | AGN09415.1 | 503 | Sequence 49 from patent US 8445248 |
| GI:13435386 | GenBank | AGV90473.1 | 503 | Sequence 25 from patent US 8524975 |
| GI:13435386 | GenBank | AHE01173.1 | 503 | Sequence 56089 from patent US 8586006 |
| GI:13435386 | GenBank | AIC48608.1 | 503 | CYP3A4, partial [synthetic construct] |
Related Sequences to LMP002675 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:13435386 | EMBL | CAA30944.1 | 503 | unnamed protein product [Homo sapiens] |
| GI:13435386 | GenBank | AAA35744.1 | 503 | cytochrome P-450 nifedipine oxidase [Homo sapiens] |
| GI:13435386 | GenBank | AAN26659.1 | 503 | Sequence 2 from patent US 6432639 |
| GI:322302351 | GenBank | AAI01632.1 | 503 | Cytochrome P450, subfamily IIIA, polypeptide 4 [Homo sapiens] |
| GI:13435386 | GenBank | ACM81594.1 | 508 | Sequence 7092 from patent US 6812339 |
| GI:13435386 | GenBank | ACM83064.1 | 508 | Sequence 8562 from patent US 6812339 |
| GI:322302351 | GenBank | ACV98997.1 | 503 | Sequence 25 from patent US 7544854 |
| GI:322302351 | GenBank | AFG98792.1 | 503 | Sequence 25 from patent US 8148599 |
| GI:322302351 | GenBank | AFQ85871.1 | 503 | Sequence 20 from patent US 8252559 |
| GI:322302351 | GenBank | AHE01173.1 | 503 | Sequence 56089 from patent US 8586006 |
| GI:322302351 | RefSeq | NP_059488.2 | 503 | cytochrome P450 3A4 isoform 1 [Homo sapiens] |
| GI:13435386 | RefSeq | NP_001189784.1 | 502 | cytochrome P450 3A4 isoform 2 [Homo sapiens] |