ITPA Antibody – Rabbit Polyclonal

This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

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. Ref.11

Catalytic activity: A nucleoside triphosphate + H2O = a nucleotide + diphosphate. HAMAP-Rule MF_03148

Cofactor: Binds 1 magnesium ion per subunit. Ref.14

Subunit structure: Homodimer. Ref.1

Subcellular location: Cytoplasm Ref.1.

Tissue specificity: Ubiquitous. Highly expressed in heart, liver, sex glands, thyroid and adrenal gland.

Involvement in disease: Inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:613850]: A common inherited condition characterized by the abnormal accumulation of inosine triphosphate in erythrocytes. It might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs.Note: The disease is caused by mutations affecting the gene represented in this entry. 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. Ref.2 Ref.15 Ref.16

Sequence similarities: Belongs to the HAM1 NTPase family.

Biophysicochemical propertiesKinetic parameters:Vmax values are similar for dITP, dHAPTP and dGTP.KM=0.51 mM for ITP Ref.1 Ref.11KM=0.31 mM for dITPKM=0.57 mM for XTPKM=40.7 µM for dHAPTPKM=933 µM for dGTPVmax=1520 µmol/min/mg enzyme for ITPVmax=940 µmol/min/mg enzyme for dITPVmax=1680 µmol/min/mg enzyme for XTPpH dependence:Optimum pH is 10.