inosine triphosphate pyrophosphatase; ITPase; inosine triphosphatase; non-canonical purine NTP pyrophosphatase; non-standard purine NTP pyrophosphatase; nucleoside-triphosphate diphosphatase; nucleoside-triphosphate pyrophosphatase; NTPase; oncogene protein hlc14-06-p (ITPA C20orf37 My049 OK/SW-cl9)
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Function
- pyrophosphatase
- hydrolyzes ITP & dITP to their respective monophosphates
- does not distinguish between deoxy- & ribose forms
- probably excludes non-canonical purines from RNA & DNA precursor pools, thus preventing their incorporation into RNA & DNA & avoiding chromosomal lesions
Cofactor: binds 1 Mg+2 per subunit
- 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
- Vmax values are similar for dITP, dHAPTP & dGTP
- pH dependence: optimum pH is 10
Structure
Compartment
Expression
- ubiquitous
- highly expressed in heart, liver, sex glands, thyroid & adrenal gland
Pathology
- defects in ITPA are the cause of ITPA deficiency
- consequences of ITPA deficiency, if any, are unknown
Polymorphism
- three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) & 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, consistent with a dimeric structure of the enzyme