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Identification
HMDB Protein ID HMDBP00431
Secondary Accession Numbers
  • 5668
  • HMDBP03327
Name Inosine triphosphate pyrophosphatase
Synonyms
  1. ITPase
  2. Inosine triphosphatase
  3. Putative oncogene protein hlc14-06-p
  4. Non-canonical purine NTP pyrophosphatase
  5. Non-standard purine NTP pyrophosphatase
  6. Nucleoside-triphosphate diphosphatase
  7. Nucleoside-triphosphate pyrophosphatase
  8. NTPase
Gene Name ITPA
Protein Type Unknown
Biological Properties
General Function Involved in hydrolase activity
Specific Function Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.
Pathways
  • Adenine phosphoribosyltransferase deficiency (APRT)
  • Adenosine Deaminase Deficiency
  • Adenylosuccinate Lyase Deficiency
  • AICA-Ribosiduria
  • Azathioprine Action Pathway
  • Beta Ureidopropionase Deficiency
  • Dihydropyrimidinase Deficiency
  • Drug metabolism - other enzymes
  • Gout or Kelley-Seegmiller Syndrome
  • Lesch-Nyhan Syndrome (LNS)
  • Mercaptopurine Action Pathway
  • Mitochondrial DNA depletion syndrome
  • MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)
  • Molybdenum Cofactor Deficiency
  • Myoadenylate deaminase deficiency
  • Purine Metabolism
  • Purine metabolism
  • Purine Nucleoside Phosphorylase Deficiency
  • Pyrimidine Metabolism
  • Pyrimidine metabolism
  • Thioguanine Action Pathway
  • UMP Synthase Deficiency (Orotic Aciduria)
  • Xanthine Dehydrogenase Deficiency (Xanthinuria)
  • Xanthinuria type I
  • Xanthinuria type II
Reactions
A nucleoside triphosphate + Water → a nucleotide + Pyrophosphate details
Guanosine triphosphate + Water → Guanosine monophosphate + Pyrophosphate details
Uridine triphosphate + Water → Uridine 5'-monophosphate + Pyrophosphate details
Inosine triphosphate + Water → Inosinic acid + Pyrophosphate details
dGTP + Water → 2'-Deoxyguanosine 5'-monophosphate + Pyrophosphate details
Deoxyuridine triphosphate + Water → dUMP + Pyrophosphate details
Xanthosine 5-triphosphate + Water → Xanthylic acid + Pyrophosphate details
2'-Deoxyinosine triphosphate + Water → dIMP + Pyrophosphate details
6-Mercaptopurine ribonucleoside triphosphate + Water → 6-Thioinosine-5'-monophosphate + Pyrophosphate details
GO Classification
Biological Process
chromosome organization
ITP catabolic process
Cellular Component
cytoplasm
Function
catalytic activity
hydrolase activity
Molecular Function
metal ion binding
dITP diphosphatase activity
nucleotide binding
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 20
Locus 20p
SNPs ITPA
Gene Sequence
>585 bp
ATGGCGGCCTCATTGGTGGGGAAGAAGATCGTGTTTGTAACGGGGAACGCCAAGAAGCTG
GAGGAGGTCGTTCAGATTCTAGGAGATAAGTTTCCATGCACTTTGGTGGCACAGAAAATT
GACCTGCCGGAGTACCAAGGGGAGCCGGATGAGATTTCCATACAGAAATGTCAGGAGGCA
GTTCGCCAGGTACAGGGGCCCGTGCTGGTTGAGGACACTTGTCTGTGCTTCAATGCCCTT
GGAGGGCTCCCCGGCCCCTACATAAAGTGGTTTCTGGAGAAGTTAAAGCCTGAAGGTCTC
CACCAGCTCCTGGCCGGGTTCGAGGACAAGTCAGCCTATGCGCTCTGCACGTTTGCACTC
AGCACCGGGGACCCAAGCCAGCCCGTGCGCCTGTTCAGGGGCCGGACCTCGGGCCGGATC
GTGGCACCCAGAGGCTGCCAGGACTTTGGCTGGGACCCCTGCTTTCAGCCTGATGGATAT
GAGCAGACGTACGCAGAGATGCCTAAGGCGGAGAAGAACGCTGTCTCCCATCGCTTCCGG
GCCCTGCTGGAGCTGCAGGAATACTTTGGCAGTTTGGCAGCTTGA
Protein Properties
Number of Residues 194
Molecular Weight 16833.23
Theoretical pI 7.174
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Inosine triphosphate pyrophosphatase
MAASLVGKKIVFVTGNAKKLEEVVQILGDKFPCTLVAQKIDLPEYQGEPDEISIQKCQEA
VRQVQGPVLVEDTCLCFNALGGLPGPYIKWFLEKLKPEGLHQLLAGFEDKSAYALCTFAL
STGDPSQPVRLFRGRTSGRIVAPRGCQDFGWDPCFQPDGYEQTYAEMPKAEKNAVSHRFR
ALLELQEYFGSLAA
GenBank ID Protein 21104378
UniProtKB/Swiss-Prot ID Q9BY32
UniProtKB/Swiss-Prot Entry Name ITPA_HUMAN
PDB IDs
GenBank Gene ID AB062127
GeneCard ID ITPA
GenAtlas ID ITPA
HGNC ID HGNC:6176
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed:11780052 ]
  3. Lin S, McLennan AG, Ying K, Wang Z, Gu S, Jin H, Wu C, Liu W, Yuan Y, Tang R, Xie Y, Mao Y: Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene. J Biol Chem. 2001 Jun 1;276(22):18695-701. Epub 2001 Mar 13. [PubMed:11278832 ]
  4. Stenmark P, Kursula P, Flodin S, Graslund S, Landry R, Nordlund P, Schuler H: Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T. J Biol Chem. 2007 Feb 2;282(5):3182-7. Epub 2006 Nov 29. [PubMed:17138556 ]
  5. Sumi S, Marinaki AM, Arenas M, Fairbanks L, Shobowale-Bakre M, Rees DC, Thein SL, Ansari A, Sanderson J, De Abreu RA, Simmonds HA, Duley JA: Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency. Hum Genet. 2002 Oct;111(4-5):360-7. Epub 2002 Aug 15. [PubMed:12384777 ]
  6. Cao H, Hegele RA: DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency. J Hum Genet. 2002;47(11):620-2. [PubMed:12436200 ]