CYP3A5

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External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
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RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
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View/Edit Human

Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.

Tissue distribution

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. 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).

Clinical significance

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.

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. 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. 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.

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. Both CYP3A4 and CYP3A5 are expressed in liver and intestine, with CYP3A5 being the predominant form expressed in extrahepatic tissues.

Allele distribution

The CYP3A5 gene has several functional variants, which vary depending on ethnicity. The CYP3A5*1 allele is associated with a normal metabolization of medication. It is most common among individuals native to Sub-Equatorial Africa, though the mutation also occurs at low frequencies in other populations. The CYP3A5*3 allele is linked with a poor metabolization of medication. It is near fixation in Europe, and is likewise found at high frequencies in West Asia and Central Asia, as well as among Afro-Asiatic (Hamitic-Semitic) speaking populations in North Africa and the Horn of Africa. Additionally, the mutation occurs at moderate-to-high frequencies in South Asia, Southeast Asia and East Asia, and at low frequencies in Sub-Equatorial Africa.

Global distribution of the CYP3A5 alleles:

Population	CYP3A5*1	CYP3A5*3	CYP3A5*6	CYP3A5*7
Adygei	12%	88%
Afar	35%	65%	18%	0%
African Americans	63%	37%	12%	21%
Algerians (North)	19%	81%	5%	1%
Amhara	33%	67%	15%	0%
Anatolian Turks	9%	91%	0%	0%
Armenians (South)	5%	95%	0%	0%
Asante	89%	11%	22%	7%
Ashkenazi Jews	3%	97%	0%	0%
Balochi	20%	80%
Bantu (Kenya)	83%	17%
Bantu (South Africa)	74%	26%	18%	10%
Bantu (Uganda)	96%	4%	22%	21%
Basques (French)	4%	96%
Bedouin (Israel)	17%	83%
Berbers (Morocco)	20%	80%	4%	1%
Biaka Pygmies	89%	11%
Brahui	12%	88%
Britons (England and Scotland)	35%	65%	0%
Bulsa	81%	19%	16%	13%
Burusho	22%	78%
Cameroonian (Lake Chad)	76%	24%	32%	7%
Canadian Caucasians	7%	93%	0%	0%
Chagga	74%	26%	14%	9%
Chewa	85%	15%	16%	17%
Chinese	25%	75%	0%
Chinese (Denver, Colorado)	25%	75%
Colombians	15%	85%
Colombians (Medellian)	48%	52%	2%
Congolese (Brazzaville)	80%	20%	12%	9%
Dai	45%	55%
Druze	8%	92%
Daur	15%	85%
East Asian	31%	69%	0%	0%
European	2%	98%	0%	0%
Finns	45%	55%	0%
French	8%-9%	91%-92%	0%	0%
Gabonese	79%	21%	19%	19%
Gambians	79%	21%	20%	12%
Germans	7%	93%
Gujarati (Houston, Texas)	25%	75%
Han	25%	75%
Han (Beijing)	28%	72%	0%
Han (Southern)	47%	53%	0%
Hazara	25%	75%
Hezhen	15%	85%
Hispanic	25%	75%	0%	0%
Iberians	39%	61%	0%
Igbo	87%	13%	18%	9%
Indians	41%	59%	0%
Italians (Bergamo)	18%	82%
Italians (Sardinia)	5%	95%
Italians (Tuscany)	5%-6%	94%-95%	0.5%
Japanese	23%	77%	0%
Japanese (Tokyo)	26%	74%	0.004%
Kalash	24%	76%
Karitiana	23%	77%
Kasena	78%	22%	17%	13%
Khmer	27%	73%
Koreans	19%	81%	0%
Kotoko	73%	27%	23%	5%
Lahu	25%	75%
Lemba	87%	13%	25%	15%
Lomwe	83%	17%	22%	11%
Luhya (Webuye, Kenya)	86%	14%	26%
Maale	51%	49%	15%	1%
Maasai (Kinyawa, Kenya)	51%	49%	14%
Makrani	14%	86%
Malay	39%	61%	0%
Malawians	79%	21%	14%	14%
Mandenka	69%	31%
Manjak	79%	21%	23%	7%
Maya	29%	71%
Mayo Darle	73%	27%	25%	6%
Mbuti Pygmies	93%	7%
Melanesians	18%	82%
Mestizo (El Salvador and Nicaragua)	24%	76%
Mestizo (Ecuador)	12%	88%
Mexicans (Los Angeles)	25%	75%	2%
Miaozu	35%	65%
Mongola	35%	65%
Mozabite	16%	84%
Naxi	28%	72%
Ngoni	89%	11%	33%	6%
North American Caucasians	9%	90%
Orogen	10%	90%
Orcadians	16%	84%
Oromo	35%	65%	14%	0%
Papuans	21%	79%
Palestinians	18%	82%
Pathan	12%	88%
Pima	54%	46%
Puerto Ricans	56%	44%	5%
Russians	8%	92%
San (Namibia)	93%	7%
Sena	84%	16%	23%	16%
Sephardi Jews	11%	89%	0%	0%
She	45%	55%
Shewa Arabs	60%	40%	22%	7%
Shona	22%	78%	22%	10%
Sindhi	18%	82%
Somie (Cameroonian Grassfields)	77%	23%	18%	10%
Southern Sudanese	76%	24%	33%	3%
Spaniard	9%	91%
Sudanese (Northern)	40%	60%	11%	0%
Sudanese (Kordofan)	55%	45%	20%	2%
Surui	17%	83%
Swedes	7%	93%	0%	0%
Tanzanians	81%	19%	19%	12%
Tu	10%	90%
Tujia	35%	65%
Tunisian	19%	81%	1%	0%
Uygur	5%	95%
Wolof	73%	27%	18%	9%
Xibo	22%	78%
Yao	82%	18%	13%	9%
Yakuts	10%	90%
Yemeni (Hadramaut)	15%	85%	3%	1%
Yemeni (Sena and Msila)	42%	58%	12%	3%
Yizu	20%	80%
Yoruba	83%-94%	6%-17%	17%-75%	0%
Zimbabweans (Mposi)	84%	16%	16%	19%

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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Irinotecan Pathway edit

See also

• Cytochrome P450

External links

• Human CYP3A5 genome location and CYP3A5 gene details page in the UCSC Genome Browser.

Further reading

• Smith G, Stubbins MJ, Harries LW, Wolf CR (December 1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica. 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
• Lee SJ, Goldstein JA (June 2005). "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, Lapenson DP, Meyer UA, Fischer V, Tyndale R, Inaba T, Kalow W, Gelboin HV (June 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". The Journal of Biological Chemistry. 264 (18): 10388–95. PMID 2732228.
• Schuetz JD, Molowa DT, Guzelian PS (November 1989). "Characterization of a cDNA encoding a new member of the glucocorticoid-responsive cytochromes P450 in human liver". Archives of Biochemistry and Biophysics. 274 (2): 355–65. doi:10.1016/0003-9861(89)90449-9. PMID 2802615.
• Murray GI, Pritchard S, Melvin WT, Burke MD (May 1995). "Cytochrome P450 CYP3A5 in the human anterior pituitary gland". FEBS Letters. 364 (1): 79–82. doi:10.1016/0014-5793(95)00367-I. PMID 7750548.
• Jounaïdi Y, Guzelian PS, Maurel P, Vilarem MJ (December 1994). "Sequence of the 5'-flanking region of CYP3A5: comparative analysis with CYP3A4 and CYP3A7". Biochemical and Biophysical Research Communications. 205 (3): 1741–7. doi:10.1006/bbrc.1994.2870. PMID 7811260.
• McKinnon RA, Burgess WM, Hall PM, Roberts-Thomson SJ, Gonzalez FJ, McManus ME (February 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, Ghosh M, Fang C, Wrighton SA, Merion RM, Watkins PB (October 1994). "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, Barnett JL, Kunze KL, Wrighton SA, Watkins PB (1995). "Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test". Drug Metabolism and Disposition. 22 (6): 947–55. PMID 7895614.
• Schuetz JD, Beach DL, Guzelian PS (February 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 (January 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, Guzelian PS, Strom S, Sun D (January 1996). "Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells". Molecular Pharmacology. 49 (1): 63–72. PMID 8569713.
• Jounaïdi Y, Hyrailles V, Gervot L, Maurel P (April 1996). "Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein?". Biochemical and Biophysical Research Communications. 221 (2): 466–70. doi:10.1006/bbrc.1996.0618. PMID 8619878.
• Hakkola J, Pasanen M, Hukkanen J, Pelkonen O, Mäenpää J, Edwards RJ, Boobis AR, Raunio H (February 1996). "Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta". Biochemical Pharmacology. 51 (4): 403–11. doi:10.1016/0006-2952(95)02184-1. PMID 8619884.
• Hakkola J, Raunio H, Purkunen R, Pelkonen O, Saarikoski S, Cresteil T, Pasanen M (July 1996). "Detection of cytochrome P450 gene expression in human placenta in first trimester of pregnancy". Biochemical Pharmacology. 52 (2): 379–83. doi:10.1016/0006-2952(96)00216-X. PMID 8694864.
• Huang Z, Fasco MJ, Figge HL, Keyomarsi K, Kaminsky LS (August 1996). "Expression of cytochromes P450 in human breast tissue and tumors". Drug Metabolism and Disposition. 24 (8): 899–905. PMID 8869826.
• Kivistö KT, Bookjans G, Fromm MF, Griese EU, Münzel P, Kroemer HK (September 1996). "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, Thummel KE, Watkins PB (October 1996). "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, Stjernvall T, Beaune P, Edwards RJ, Boobis AR, Pelkonen O, Raunio H (March 1997). "Expression and localization of CYP3A4 and CYP3A5 in human lung". American Journal of Respiratory Cell and Molecular Biology. 16 (3): 242–9. doi:10.1165/ajrcmb.16.3.9070608. PMID 9070608.
• Hukkanen J, Hakkola J, Anttila S, Piipari R, Karjalainen A, Pelkonen O, Raunio H (October 1997). "Detection of mRNA encoding xenobiotic-metabolizing cytochrome P450s in human bronchoalveolar macrophages and peripheral blood lymphocytes". Molecular Carcinogenesis. 20 (2): 224–30. doi:10.1002/(SICI)1098-2744(199710)20:2<224::AID-MC9>3.0.CO;2-M. PMID 9364212.