CYP3A5

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CYP3A5
Identifiers
Aliases CYP3A5, CP35, CYPIIIA5, P450PCN3, PCN3, cytochrome P450 family 3 subfamily A member 5
External IDs MGI: 2449818 HomoloGene: 133568 GeneCards: CYP3A5
Targeted by Drug
ritonavir[1]
RNA expression pattern
PBB GE CYP3A5 214234 s at fs.png

PBB GE CYP3A5 205765 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000777
NM_001190484
NM_001291829
NM_001291830

NM_177380

RefSeq (protein)

NP_000768
NP_001177413
NP_001278758
NP_001278759

n/a

Location (UCSC) Chr 7: 99.65 – 99.68 Mb Chr 5: 145.77 – 145.81 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

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

Tissue distribution[edit]

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.[4] 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).[4]

Clinical significance[edit]

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.[5]

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.[4] 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.[6] 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.[7]

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.[8] Both CYP3A4 and CYP3A5 are expressed in liver and intestine, with CYP3A5 being the predominant form expressed in extrahepatic tissues.[8]

Allele distribution[edit]

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.[9][10]

Global distribution of the CYP3A5 alleles:[10]

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[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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IrinotecanPathway_WP46359 go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article Go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article Go to article go to article
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IrinotecanPathway_WP46359 go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article Go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article Go to article go to article
|{{{bSize}}}px|alt=Irinotecan Pathway edit]]
  1. ^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP46359". 

See also[edit]

References[edit]

  1. ^ "Drugs that physically interact with Cytochrome P450 family 3 subfamily A member 5 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ a b c "P08684-CP3A4_Human". UniProt. UniProt. Retrieved November 2014.  Check date values in: |access-date= (help)
  5. ^ "Entrez Gene: CYP3A5 cytochrome P450, family 3, subfamily A, polypeptide 5". 
  6. ^ "CYTOCHROME P450, SUBFAMILY IIIA, POLYPEPTIDE 5; CYP3A5". OMIM. Retrieved November 2014.  Check date values in: |access-date= (help)
  7. ^ Zanger UM, Turpeinen M, Klein K, Schwab M (2008). "Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation". Analytical and Bioanalytical Chemistry. 392 (6): 1093–108. doi:10.1007/s00216-008-2291-6. PMID 18695978. 
  8. ^ a b "CYP3A5". PharmGKB. Retrieved November 2014.  Check date values in: |access-date= (help)
  9. ^ Valente C, Alvarez L, Marks SJ, Lopez-Parra AM, Parson W, Oosthuizen O, Oosthuizen E, Amorim A, Capelli C, Arroyo-Pardo E, Gusmão L, Prata MJ (28 May 2015). "Exploring the relationship between lifestyles, diets and genetic adaptations in humans". BMC Genetics. 16 (55): 55. doi:10.1186/s12863-015-0212-1. PMC 4445807Freely accessible. PMID 26018448. 
  10. ^ a b Bains, Ripudaman Kaur. "Molecular diversity and population structure at the CYP3A5 gene in Africa" (PDF). University College London. Retrieved 13 June 2016. 

Further reading[edit]

  • 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 1382414Freely accessible. 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 2042681Freely accessible. 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.