ID:ITPA_HUMAN DESCRIPTION: RecName: Full=Inosine triphosphate pyrophosphatase; Short=ITPase; Short=Inosine triphosphatase; EC=3.6.1.19; AltName: Full=Non-canonical purine NTP pyrophosphatase; AltName: Full=Non-standard purine NTP pyrophosphatase; AltName: Full=Nucleoside-triphosphate diphosphatase; AltName: Full=Nucleoside-triphosphate pyrophosphatase; Short=NTPase; AltName: Full=Putative oncogene protein hlc14-06-p; 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. CATALYTIC ACTIVITY: A nucleoside triphosphate + H(2)O = a nucleotide + diphosphate. COFACTOR: Binds 1 magnesium ion per subunit. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.51 mM for ITP; KM=0.31 mM for dITP; KM=0.57 mM for XTP; KM=40.7 uM for dHAPTP; KM=933 uM for dGTP; Vmax=1520 umol/min/mg enzyme for ITP; Vmax=940 umol/min/mg enzyme for dITP; Vmax=1680 umol/min/mg enzyme for XTP; Note=Vmax values are similar for dITP, dHAPTP and dGTP; pH dependence: Optimum pH is 10; SUBUNIT: Homodimer. SUBCELLULAR LOCATION: Cytoplasm. TISSUE SPECIFICITY: Ubiquitous. Highly expressed in heart, liver, sex glands, thyroid and adrenal gland. DISEASE: Defects in ITPA are the cause of inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:613850]. It is a common inherited trait characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes and also leukocytes and fibroblasts. The pathological consequences of ITPA deficiency, if any, are unknown. However, it might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs. Note=Three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) and low activity. The variant Thr-32 is associated with complete loss of enzyme activity, may be by altering the local secondary structure of the protein. Heterozygotes for this polymorphism have 22.5% of the control activity: this is consistent with a dimeric structure of the enzyme. SIMILARITY: Belongs to the HAM1 NTPase family.
Protein Domain and Structure Information
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Other Names for This Gene
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Methods, Credits, and Use Restrictions
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for details on how this gene model was made and data restrictions if any.
