ITPA

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] 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.

ITPA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CAR, 2I5D, 2J4E, 4F95
Identifiers
Aliases	ITPA, C20orf37, HLC14-06-P, dJ794I6.3, My049, ITPase, NTPase, inosine triphosphatase
External IDs	OMIM: 147520 MGI: 96622 HomoloGene: 6289 GeneCards: ITPA
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20p13 Start 3,208,868 bp[1] End 3,223,870 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 F1|2 63.24 cM Start 130,667,610 bp[2] End 130,681,614 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • dITP diphosphatase activity • XTP diphosphatase activity • ITP diphosphatase activity • hydrolase activity • metal ion binding • nucleotide diphosphatase activity • NADH pyrophosphatase activity • nucleoside-triphosphate diphosphatase activity • identical protein binding Cellular component • cytoplasm • cytosol Biological process • ITP catabolic process • nucleotide metabolic process • chromosome organization • nucleoside triphosphate catabolic process • purine nucleotide catabolic process • deoxyribonucleoside triphosphate catabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3704	16434
Ensembl	ENSG00000125877	ENSMUSG00000074797
UniProt	Q9BY32	Q9D892
RefSeq (mRNA)	NM_001267623 NM_033453 NM_181493 NM_001324236 NM_001324237 NM_001324238 NM_001324240 NM_001351739	NM_025922 NM_001362648
RefSeq (protein)	NP_001254552 NP_001311165 NP_001311166 NP_001311167 NP_001311169 NP_258412 NP_852470 NP_001338668	NP_080198 NP_001349577
Location (UCSC)	Chr 20: 3.21 – 3.22 Mb	Chr 2: 130.67 – 130.68 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate.[6] The enzyme possesses a multiple substrate-specificity 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]

References

1. GRCh38: Ensembl release 89: ENSG00000125877 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000074797 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lin S, McLennan AG, Ying K, Wang Z, Gu S, Jin H, Wu C, Liu W, Yuan Y, Tang R, Xie Y, Mao Y (May 2001). "Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene". J Biol Chem. 276 (22): 18695–701. doi:10.1074/jbc.M011084200. PMID 11278832.
6. "Entrez Gene: ITPA inosine triphosphatase (nucleoside triphosphate pyrophosphatase)".
7. Burgis NE, Cunningham RP (2007). "Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate pyrophosphohydrolase". J Biol Chem. 282 (8): 3531–8. doi:10.1074/jbc.M608708200. PMID 17090528.
8. Davies O, Mendes P, Smallbone K, Malys N (2012). "Characterisation of multiple substrate-specific (d)ITP/(d)XTPase and modelling of deaminated purine nucleotide metabolism". BMB Reports. 45 (4): 259–64. doi:10.5483/BMBRep.2012.45.4.259. PMID 22531138.

Further reading

• Holmes SL, Turner BM, Hirschhorn K (1979). "Human inosine triphosphatase: catalytic properties and population studies". Clin. Chim. Acta. 97 (2–3): 143–53. doi:10.1016/0009-8981(79)90410-8. PMID 487601.
• Fraser JH, Meyers H, Henderson JF, et al. (1976). "Individual variation in inosine triphosphate accumulation in human erythrocytes". Clin. Biochem. 8 (6): 353–64. doi:10.1016/S0009-9120(75)93685-1. PMID 1204209.
• Clawson GA, Song YL, Schwartz AM, et al. (1992). "Interaction of human immunodeficiency virus type I Rev protein with nuclear scaffold nucleoside triphosphatase activity". Cell Growth Differ. 2 (11): 575–82. PMID 1667585.
• Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
• Sumi S, Marinaki AM, Arenas M, et al. (2002). "Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency". Hum. Genet. 111 (4–5): 360–7. 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". J. Hum. Genet. 47 (11): 620–2. doi:10.1007/s100380200095. PMID 12436200.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Marinaki AM, Duley JA, Arenas M, et al. (2005). "Mutation in the ITPA gene predicts intolerance to azathioprine". Nucleosides Nucleotides Nucleic Acids. 23 (8–9): 1393–7. doi:10.1081/NCN-200027639. PMID 15571265. S2CID 86308163.
• Marinaki AM, Sumi S, Arenas M, et al. (2005). "Allele frequency of inosine triphosphate pyrophosphatase gene polymorphisms in a Japanese population". Nucleosides Nucleotides Nucleic Acids. 23 (8–9): 1399–401. doi:10.1081/NCN-200027641. PMID 15571266. S2CID 36126159.
• Maeda T, Sumi S, Ueta A, et al. (2005). "Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population". Mol. Genet. Metab. 85 (4): 271–9. 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 Transpl. 11 (7): 826–33. doi:10.1002/lt.20377. PMID 15973722. S2CID 9301778.
• Porta J, Kolar C, Kozmin SG, et al. (2006). "Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase". Acta Crystallographica Section F. 62 (Pt 11): 1076–81. doi:10.1107/S1744309106041790. PMC 2225220. PMID 17077483.
• Arenas M, Duley J, Sumi S, et al. (2007). "The ITPA c.94C>A and g.IVS2+21A>C sequence variants contribute to missplicing of the ITPA gene". Biochim. Biophys. Acta. 1772 (1): 96–102. doi:10.1016/j.bbadis.2006.10.006. PMID 17113761.
• Stenmark P, Kursula P, Flodin S, et al. (2007). "Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T". J. Biol. Chem. 282 (5): 3182–7. doi:10.1074/jbc.M609838200. PMID 17138556.
• Atanasova S, Shipkova M, Svinarov D, et al. (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.