CYP3A5
| Cytochrome P450, family 3, subfamily A, polypeptide 5 | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | CYP3A5 ; CP35; CYPIIIA5; P450PCN3; PCN3 | ||||||||||||
| External IDs | OMIM: 605325 MGI: 88609 HomoloGene: 133568 ChEMBL: 3019 GeneCards: CYP3A5 Gene | ||||||||||||
| EC number | 1.14.14.1 | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 1577 | 13112 | |||||||||||
| Ensembl | ENSG00000106258 | ENSMUSG00000056035 | |||||||||||
| UniProt | P20815 | Q64459 | |||||||||||
| RefSeq (mRNA) | NM_000777 | NM_007818 | |||||||||||
| RefSeq (protein) | NP_000768 | NP_031844 | |||||||||||
| Location (UCSC) |
Chr 7: 99.65 – 99.68 Mb |
Chr 5: 145.85 – 145.88 Mb | |||||||||||
| PubMed search | |||||||||||||
Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.
CYP3A5 encodes a member of the cytochrome P450 superfamily of enzymes. Like most of the Cytochrome P450, the CYP3A5 is expressed in the prostate and the liver.[1] It is also expressed in epithelium of the small intestine and large intestine for uptake and in small amounts in the 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).[1] The cytochrome P450 proteins are monooxygenases which 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. The enzyme metabolizes drugs such as nifedipine and cyclosporine as well as the steroid hormones testosterone, progesterone and androstenedione. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. This cluster includes a pseudogene, CYP3A5P1, which is very similar to CYP3A5. This similarity has caused some difficulty in determining whether cloned sequences represent the gene or the pseudogene.[2] CYP3A4/3A5 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.[1] Immunoblot analysis of liver microsomes showed that CYP3A5 is expressed as a 52.5-kD protein, whereas CYP3A4 migrates as a 52.0-kD protein.[3]The human CYP3A subfamily, CYP3A4, CYP3A5, CYP3A7 and CYP3A43, is one of the most versatile of the biotransformation systems that facilitate the elimination of drugs (37% of the 200 most frequently prescribed drugs in the U.S.[4]CYP3A4 and CYP3A5 together account for approximately 30% of hepatic cytochrome P450, and approximately half of medications that are oxidatively metabolized by P450 are CYP3A substrates.[5] Both CYP3A4 and CYP3A5 are expressed in liver and intestine, with CYP3A5 being the predominant form expressed in extrahepatic tissues.[6]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Irinotecan Pathway edit
- ↑ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP46359".
See also
References
- 1 2 3 "P08684-CP3A4_Human". UniProt. UniProt. Retrieved November 2014.
- ↑ "Entrez Gene: CYP3A5 cytochrome P450, family 3, subfamily A, polypeptide 5".
- ↑ "CYTOCHROME P450, SUBFAMILY IIIA, POLYPEPTIDE 5; CYP3A5". OMIM. Retrieved November 2014.
- ↑ Zanger, Ulrich M; Turpeinen, Miia; Klein, Kathrin; Schwab, Matthias. "Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation". PharmGKB. Retrieved November 2014.
- ↑ "CYP3A5". PharmGKB. Retrieved November 2014.
- ↑ "CYP3A5". PharmGKB. Retrieved November 2014.
Further reading
- Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily.". Xenobiotica 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
- Lee SJ, Goldstein JA (2006). "Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests.". Pharmacogenomics 6 (4): 357–71. doi:10.1517/14622416.6.4.357. PMID 16004554.
- Aoyama T, Yamano S, Waxman DJ; et al. (1989). "Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine.". J. Biol. Chem. 264 (18): 10388–95. PMID 2732228.
- Schuetz JD, Molowa DT, Guzelian PS (1989). "Characterization of a cDNA encoding a new member of the glucocorticoid-responsive cytochromes P450 in human liver.". Arch. Biochem. Biophys. 274 (2): 355–65. doi:10.1016/0003-9861(89)90449-9. PMID 2802615.
- Murray GI, Pritchard S, Melvin WT, Burke MD (1995). "Cytochrome P450 CYP3A5 in the human anterior pituitary gland.". FEBS Lett. 364 (1): 79–82. doi:10.1016/0014-5793(95)00367-I. PMID 7750548.
- Jounaïdi Y, Guzelian PS, Maurel P, Vilarem MJ (1995). "Sequence of the 5'-flanking region of CYP3A5: comparative analysis with CYP3A4 and CYP3A7.". Biochem. Biophys. Res. Commun. 205 (3): 1741–7. doi:10.1006/bbrc.1994.2870. PMID 7811260.
- McKinnon RA, Burgess WM, Hall PM; et al. (1995). "Characterisation of CYP3A gene subfamily expression in human gastrointestinal tissues.". Gut 36 (2): 259–67. doi:10.1136/gut.36.2.259. PMC 1382414. PMID 7883227.
- Kolars JC, Lown KS, Schmiedlin-Ren P; et al. (1995). "CYP3A gene expression in human gut epithelium.". Pharmacogenetics 4 (5): 247–59. doi:10.1097/00008571-199410000-00003. PMID 7894497.
- Lown KS, Kolars JC, Thummel KE; et al. (1995). "Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test.". Drug Metab. Dispos. 22 (6): 947–55. PMID 7895614.
- Schuetz JD, Beach DL, Guzelian PS (1994). "Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver.". Pharmacogenetics 4 (1): 11–20. doi:10.1097/00008571-199402000-00002. PMID 8004129.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Schuetz JD, Schuetz EG, Thottassery JV; et al. (1996). "Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells.". Mol. Pharmacol. 49 (1): 63–72. PMID 8569713.
- Jounaïdi Y, Hyrailles V, Gervot L, Maurel P (1996). "Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein?". Biochem. Biophys. Res. Commun. 221 (2): 466–70. doi:10.1006/bbrc.1996.0618. PMID 8619878.
- Hakkola J, Pasanen M, Hukkanen J; et al. (1996). "Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta.". Biochem. Pharmacol. 51 (4): 403–11. doi:10.1016/0006-2952(95)02184-1. PMID 8619884.
- Hakkola J, Raunio H, Purkunen R; et al. (1996). "Detection of cytochrome P450 gene expression in human placenta in first trimester of pregnancy.". Biochem. Pharmacol. 52 (2): 379–83. doi:10.1016/0006-2952(96)00216-X. PMID 8694864.
- Huang Z, Fasco MJ, Figge HL; et al. (1997). "Expression of cytochromes P450 in human breast tissue and tumors.". Drug Metab. Dispos. 24 (8): 899–905. PMID 8869826.
- Kivistö KT, Bookjans G, Fromm MF; et al. (1997). "Expression of CYP3A4, CYP3A5 and CYP3A7 in human duodenal tissue.". British Journal of Clinical Pharmacology 42 (3): 387–9. doi:10.1046/j.1365-2125.1996.42615.x. PMC 2042681. PMID 8877031.
- Janardan SK, Lown KS, Schmiedlin-Ren P; et al. (1997). "Selective expression of CYP3A5 and not CYP3A4 in human blood.". Pharmacogenetics 6 (5): 379–85. doi:10.1097/00008571-199610000-00001. PMID 8946469.
- Anttila S, Hukkanen J, Hakkola J; et al. (1997). "Expression and localization of CYP3A4 and CYP3A5 in human lung.". Am. J. Respir. Cell Mol. Biol. 16 (3): 242–9. doi:10.1165/ajrcmb.16.3.9070608. PMID 9070608.
- Hukkanen J, Hakkola J, Anttila S; et al. (1997). "Detection of mRNA encoding xenobiotic-metabolizing cytochrome P450s in human bronchoalveolar macrophages and peripheral blood lymphocytes.". Mol. Carcinog. 20 (2): 224–30. doi:10.1002/(SICI)1098-2744(199710)20:2<224::AID-MC9>3.0.CO;2-M. PMID 9364212.
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