ITPA

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, DEE35
External IDs	OMIM: 147520; MGI: 96622; HomoloGene: 6289; GeneCards: ITPA; OMA:ITPA - orthologs
Gene location (Human)
Chr.	Chromosome 20 (human)
End	3,223,870 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	130,523,534 bp
RNA expression pattern
	Top expressed in
	right lobe of thyroid gland; ; left lobe of thyroid gland; ; mucosa of transverse colon; ; right adrenal cortex; ; right uterine tube; ; left adrenal gland; ; left adrenal cortex; ; mucosa of esophagus; ; granulocyte; ; skin of leg;
	Top expressed in
	embryo; ; embryo; ; ventricular zone; ; endocardial cushion; ; epiblast; ; primitive streak; ; morula; ; ganglionic eminence; ; neural tube; ; otic placode;
	More reference expression data
	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
	3704
	16434
	ENSG00000125877
	ENSMUSG00000074797
	Q9BY32
	Q9D892
NM_001267623 ; NM_033453 ; NM_181493 ; NM_001324236 ; NM_001324237 ;
	NM_001324238 ; NM_001324240 ; NM_001351739
	NM_025922 ; NM_001362648
NP_001254552 ; NP_001311165 ; NP_001311166 ; NP_001311167 ; NP_001311169 ;
	NP_258412 ; NP_852470 ; NP_001338668
	NP_080198 ; NP_001349577
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 14, 2025

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 ]}

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]

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, 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>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.

Related Research Articles

Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

<span class="mw-page-title-main">Ribavirin</span> Antiviral medication

Ribavirin, also known as tribavirin, is an antiviral medication used to treat illness caused by respiratory syncytial virus (RSV) and hepatitis C virus (HCV) infections, as well as some viral hemorrhagic fevers. For HCV, it is used in combination with other medications, such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. It can also be used for viral hemorrhagic fevers—specifically, for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infections. Ribavirin is usually taken orally or inhaled. Despite widespread usage, it has faced scrutiny in the 21st century because of lack of proven efficacy in treating viral infections for which it has been prescribed in the past.

Inosinic acid or inosine monophosphate (IMP) is a nucleotide. Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine nucleotides. It can also be formed by the deamination of adenosine monophosphate by AMP deaminase. It can be hydrolysed to inosine.

<span class="mw-page-title-main">Purine nucleoside phosphorylase</span> Enzyme

Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase is an enzyme that in humans is encoded by the NP gene. It catalyzes the chemical reaction

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">Nucleoside-diphosphatase</span> Group of proteins having nucleoside-diphosphatase activity

In enzymology, a nucleoside-diphosphatase (EC 3.6.1.6) is an enzyme that catalyzes the chemical reaction

In enzymology, a nucleoside-triphosphate diphosphatase (EC 3.6.1.19) is an enzyme that catalyzes the chemical reaction

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 is an enzyme that in humans is encoded by the ENPP1 gene.

Cytosolic 5'-nucleotidase 3 (NT5C3), also known as cytosolic 5'-nucleotidase 3A, pyrimidine 5’-nucleotidase, and p56, is an enzyme that in humans is encoded by the NT5C3, or NT5C3A, gene on chromosome 7.

dCTP pyrophosphatase 1 is an enzyme that in humans is encoded by the DCTPP1 gene.

Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical] is an enzyme that in humans is encoded by the NUDT2 gene.

Molybdenum cofactor synthesis protein 2A and molybdenum cofactor synthesis protein 2B are a pair of proteins that in humans are encoded from the same MOCS2 gene. These two proteins dimerize to form molybdopterin synthase.

Ectonucleoside triphosphate diphosphohydrolase 6 is an enzyme that in humans is encoded by the ENTPD6 gene.

CTP synthase 1 is an enzyme that is encoded by the CTPS1 gene in humans. CTP synthase 1 is an enzyme in the de novo pyrimidine synthesis pathway that catalyses the conversion of uridine triphosphate (UTP) to cytidine triphosphate (CTP). CTP is a key building block for the production of DNA, RNA and some phospholipids.

NOD-like receptor family pyrin domain containing 11 is a protein that in humans is encoded by the NLRP11 gene located on the long arm of human chromosome 19q13.42. NLRP11 belongs to the NALP subfamily, part of a large subfamily of CATERPILLER. It is also known as NALP11, PYPAF6, NOD17, PAN10, and CLR19.6

Interferon lambda 3 encodes the IFNL3 protein. IFNL3 was formerly named IL28B, but the Human Genome Organization Gene Nomenclature Committee renamed this gene in 2013 while assigning a name to the then newly discovered IFNL4 gene. Together with IFNL1 and IFNL2, these genes lie in a cluster on chromosomal region 19q13. IFNL3 shares ~96% amino-acid identity with IFNL2, ~80% identity with IFNL1 and ~30% identity with IFNL4.

2-hydroxy-dATP diphosphatase is an enzyme that in humans is encoded by the NUDT1 gene. During DNA repair, the enzyme hydrolyses oxidized purines and prevents their addition onto the DNA chain. As such it has important role in aging and cancer development.

Deoxyinosine monophosphate (dIMP) is a nucleoside monophosphate and a derivative of inosinic acid. It can be formed by the deamination of the purine base in deoxyadenosine monophosphate (dAMP). The enzyme deoxyribonucleoside triphosphate pyrophosphohydrolase, encoded by YJR069C in S. cerevisiae and containing (d)ITPase and (d)XTPase activities, hydrolyses dITP, resulting in the release of pyrophosphate and dIMP.

Inosine triphosphate (ITP) is an intermediate in the purine metabolism pathway, seen in the synthesis of ATP and GTP. It comprises an inosine nucleotide containing three phosphate groups esterified to the sugar moiety.

Hermione Anne Simmonds was a New Zealand biochemist, who worked mostly in the United Kingdom. She was an expert in inborn errors of purine and pyrimidine metabolism, publishing more than 400 papers and book chapters. Simmonds was a co-founder of the Purine and Pyrimidine Society, the Purine Metabolic Patients' Association and the Association of Researchers in Medical Science.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000125877 – Ensembl, May 2017
1 2 3 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.
1 2 3 "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.
1 2 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, Daròs 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.
↑ Nyström K, Wanrooij PH, Waldenström 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, Nyström 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.

This article on a gene on human chromosome 20 is a stub. You can help Wikipedia by expanding it.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000125877 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[pmid11278832-5] 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.

[entrez-6] 1 2 3 "Entrez Gene: ITPA inosine triphosphatase (nucleoside triphosphate pyrophosphatase)".

[pmid_17090528-7] 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.

[pmid_22531138-8] 1 2 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.

[9] Pasin F, Daròs 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.

[10] Nyström K, Wanrooij PH, Waldenström 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.

[11] Rembeck K, Waldenstrom J, Hellstrand K, Nilsson S, Nyström 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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]