Inosine triphosphate pyrophosphatase is an enzyme that in humans is encoded by the ITPAgene,[5][6] by the rdgBgene in bacteria E.coli[7] and the HAM1gene 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]
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 significanceedit
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 ITPase reduced enzymatic activity present 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]
Readingedit
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, Brox LW, McCoy EE (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, Shukla RR, Patel SG, Connor L, 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, Burton J, Gilbert JG, Jones M, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi:10.1038/414865a. PMID 11780052.
Sumi S, Marinaki AM, Arenas M, Fairbanks L, Shobowale-Bakre M, Rees D, 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, Derge JG, Klausner RD, Collins FS, 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, 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. PMC528928. PMID 15489334.
Marinaki AM, Duley JA, Arenas M, Ansari A, Sumi S, Lewis CM, 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, Fairbanks L, Harihara S, Shimizu K, 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, Ohkubo Y, Ito T, Marinaki AM, 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, Pavlov YI, Borgstahl GE (2006). "Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase". Acta Crystallographica Section F. 62 (Pt 11): 1076–81. doi:10.1107/S1744309106041790. PMC2225220. PMID 17077483.
Arenas M, Duley J, Sumi S, Sanderson J, Marinaki A (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, Graslund S, Landry R, Nordlund P, 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, Mladenova A, Genova M, Wieland E, 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.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000125877 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000074797 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Lin S, McLennan AG, Ying K, Wang Z, Gu S, Jin H, et al. (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.
itpa, inosine, triphosphate, pyrophosphatase, enzyme, that, humans, encoded, gene, rdgb, gene, bacteria, coli, ham1, gene, yeast, cerevisiae, protein, also, encoded, some, viruses, potyviridae, family, transcript, variants, encoding, different, isoforms, have,. 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 ITPAAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes2CAR 2I5D 2J4E 4F95IdentifiersAliasesITPA C20orf37 HLC14 06 P dJ794I6 3 My049 ITPase NTPase inosine triphosphatase DEE35External IDsOMIM 147520 MGI 96622 HomoloGene 6289 GeneCards ITPAGene location Human Chr Chromosome 20 human 1 Band20p13Start3 208 868 bp 1 End3 223 870 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 F1 2 63 24 cMStart130 509 530 bp 2 End130 523 534 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright lobe of thyroid glandleft lobe of thyroid glandright uterine tubeleft adrenal glandskin of abdomenminor salivary glandspleenbody of stomachmonocytebody of pancreasTop expressed inendocardial cushionprimitive streakmorulaganglionic eminenceneural tubeotic placodemaxillary prominenceabdominal wallatrioventricular valvemedial ganglionic eminenceMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionnucleotide 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 bindingCellular componentcytoplasm cytosolBiological processITP catabolic process nucleotide metabolic process chromosome organization nucleoside triphosphate catabolic process purine nucleotide catabolic process deoxyribonucleoside triphosphate catabolic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez370416434EnsemblENSG00000125877ENSMUSG00000074797UniProtQ9BY32Q9D892RefSeq mRNA NM 001267623NM 033453NM 181493NM 001324236NM 001324237NM 001324238NM 001324240NM 001351739NM 025922NM 001362648RefSeq protein NP 001254552NP 001311165NP 001311166NP 001311167NP 001311169NP 258412NP 852470NP 001338668NP 080198NP 001349577Location UCSC Chr 20 3 21 3 22 MbChr 2 130 51 130 52 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 Reading 4 ReferencesFunction editThe 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 editDefects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency 6 The enzyme ITPase dephosphorylates ribavirin triphosphate in vitro to ribavirin monophosphate and ITPase reduced enzymatic activity present 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 Reading editHolmes 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 Brox LW McCoy EE 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 Shukla RR Patel SG Connor L 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 Burton J Gilbert JG Jones M et al 2002 The DNA sequence and comparative analysis of human chromosome 20 Nature 414 6866 865 71 Bibcode 2001Natur 414 865D doi 10 1038 414865a PMID 11780052 Sumi S Marinaki AM Arenas M Fairbanks L Shobowale Bakre M Rees D 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 Derge JG Klausner RD Collins FS 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 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Gerhard DS Wagner L Feingold EA Shenmen CM Grouse LH Schuler G 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 Ansari A Sumi S Lewis CM 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 Fairbanks L Harihara S Shimizu K 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 Ohkubo Y Ito T Marinaki AM 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 Pavlov YI Borgstahl GE 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 Sanderson J Marinaki A 2007 The ITPA c 94C gt A and g IVS2 21A gt 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 Graslund S Landry R Nordlund P 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 Mladenova A Genova M Wieland E 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 References edit a b c GRCh38 Ensembl release 89 ENSG00000125877 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000074797 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Lin S McLennan AG Ying K Wang Z Gu S Jin H et al 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 a b c Entrez Gene ITPA inosine triphosphatase nucleoside triphosphate pyrophosphatase 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 a b 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 Pasin F Daros JA Tzanetakis IE 2022 Proteome expansion in the Potyviridae evolutionary radiation FEMS Microbiology Reviews 46 4 fuac011 doi 10 1093 femsre fuac011 ISSN 1574 6976 PMC 9249622 PMID 35195244 Nystrom K Wanrooij PH Waldenstrom J Adamek L Brunet S Said J et al October 2018 Inosine Triphosphate Pyrophosphatase Dephosphorylates Ribavirin Triphosphate and Reduced Enzymatic Activity Potentiates Mutagenesis in Hepatitis C Virus Journal of Virology 92 19 01087 18 doi 10 1002 hep 27009 PMC 6146798 PMID 30045981 Rembeck K Waldenstrom J Hellstrand K Nilsson S Nystrom K Martner A et al June 2014 Variants of the inosine triphosphate pyrophosphatase gene are associated with reduced relapse risk following treatment for HCV genotype 2 3 Hepatology 59 6 2131 2139 doi 10 1002 hep 27009 PMID 24519039 nbsp This article on a gene on human chromosome 20 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title ITPA amp oldid 1217007412, wikipedia, wiki, book, books, library,
