ITPA
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
Inosine triphosphate pyrophosphatase is an enzyme that in humans is encoded by the ITPA gene,[5][6] by the rdgB gene in bacteria E.coli[7] and the HAM1 gene in yeast S. cerevisiae;[8] the protein is also encoded by some RNA viruses of the Potyviridae family.[9] Two transcript variants encoding two different isoforms have been found for this gene. Also, at least two other transcript variants have been identified which are probably regulatory rather than protein-coding.[citation needed]
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| Aliases | ITPA, C20orf37, HLC14-06-P, dJ794I6.3, My049, ITPase, NTPase, inosine triphosphatase, DEE35 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 147520; MGI: 96622; GeneCards: ITPA | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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Function
The protein encoded by this gene hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate.[6] The enzyme possesses specificity to multiple substrates, and acts on other nucleotides including xanthosine triphosphate and deoxyxanthosine triphosphate.[8] The encoded protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer.
Clinical significance
Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency.[6] The enzyme ITPase dephosphorylates ribavirin triphosphate in vitro to ribavirin monophosphate, and reduced ITPase activity in 30% of humans potentiates mutagenesis in hepatitis C virus.[10] Gene variants predicting reduced predicted ITPase activity have been associated with decreased risk of ribavirin-induced anemia, increased risk of thrombocytopenia, lower ribavirin concentrations, as well as a ribavirin-like reduced relapse risk following interferon-based therapy for hepatitis C virus (HCV) genotype 2 or 3 infection.[11]
Further reading
- Holmes SL, Turner BM, Hirschhorn K (1979). "Human inosine triphosphatase: catalytic properties and population studies". Clinica Chimica Acta; International Journal of Clinical Chemistry. 97 (2–3): 143–153. doi:10.1016/0009-8981(79)90410-8. PMID 487601.
- Fraser JH, Meyers H, Henderson JF, Brox LW, McCoy EE (December 1975). "Individual variation in inosine triphosphate accumulation in human erythrocytes". Clinical Biochemistry. 8 (6): 353–364. doi:10.1016/S0009-9120(75)93685-1. PMID 1204209.
- Clawson GA, Song YL, Schwartz AM, Shukla RR, Patel SG, Connor L, et al. (November 1991). "Interaction of human immunodeficiency virus type I Rev protein with nuclear scaffold nucleoside triphosphatase activity". Cell Growth & Differentiation. 2 (11): 575–582. PMID 1667585.
- Sumi S, Marinaki AM, Arenas M, Fairbanks L, Shobowale-Bakre M, Rees DC, et al. (October 2002). "Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency". Human Genetics. 111 (4–5): 360–367. doi:10.1007/s00439-002-0798-z. PMID 12384777. S2CID 24240940.
- Cao H, Hegele RA (2003). "DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency". Journal of Human Genetics. 47 (11): 620–622. doi:10.1007/s100380200095. PMID 12436200.
- Marinaki AM, Duley JA, Arenas M, Ansari A, Sumi S, Lewis CM, et al. (October 2004). "Mutation in the ITPA gene predicts intolerance to azathioprine". Nucleosides, Nucleotides & Nucleic Acids. 23 (8–9): 1393–1397. doi:10.1081/NCN-200027639. PMID 15571265. S2CID 86308163.
- Marinaki AM, Sumi S, Arenas M, Fairbanks L, Harihara S, Shimizu K, et al. (October 2004). "Allele frequency of inosine triphosphate pyrophosphatase gene polymorphisms in a Japanese population". Nucleosides, Nucleotides & Nucleic Acids. 23 (8–9): 1399–1401. doi:10.1081/NCN-200027641. PMID 15571266. S2CID 36126159.
- Maeda T, Sumi S, Ueta A, Ohkubo Y, Ito T, Marinaki AM, et al. (August 2005). "Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population". Molecular Genetics and Metabolism. 85 (4): 271–279. doi:10.1016/j.ymgme.2005.03.011. PMID 15946879.
- Breen DP, Marinaki AM, Arenas M, Hayes PC (2005). "Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation". Liver Transplantation. 11 (7): 826–833. doi:10.1002/lt.20377. PMID 15973722. S2CID 9301778.
- Porta J, Kolar C, Kozmin SG, Pavlov YI, Borgstahl GE (November 2006). "Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications. 62 (Pt 11): 1076–1081. doi:10.1107/S1744309106041790. PMC 2225220. PMID 17077483.
- Arenas M, Duley J, Sumi S, Sanderson J, Marinaki A (January 2007). "The ITPA c.94C>A and g.IVS2+21A>C sequence variants contribute to missplicing of the ITPA gene". Biochimica et Biophysica Acta. 1772 (1): 96–102. doi:10.1016/j.bbadis.2006.10.006. PMID 17113761.
- Stenmark P, Kursula P, Flodin S, Gräslund S, Landry R, Nordlund P, et al. (February 2007). "Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T". The Journal of Biological Chemistry. 282 (5): 3182–3187. doi:10.1074/jbc.M609838200. PMID 17138556.
- Atanasova S, Shipkova M, Svinarov D, Mladenova A, Genova M, Wieland E, et al. (February 2007). "Analysis of ITPA phenotype-genotype correlation in the Bulgarian population revealed a novel gene variant in exon 6". Therapeutic Drug Monitoring. 29 (1): 6–10. doi:10.1097/FTD.0b013e3180308554. PMID 17304144. S2CID 7286658.
