Genetic studies of human erythrocyte inosine triphosphatase

Vanderheiden, Bernardo S.

doi:10.1007/bf00521144

Cited by 64 publications

(29 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subject GM1617 was a 29-year-old woman with complete ITP-ase deficiency originally reported by Vanderheiden (1969). DNA from five normal Caucasian control subjects was also sequenced.…”

Section: Methodsmentioning

confidence: 99%

“…ITP-ase is a nucleoside triphosphate pyrophosphohydrolase that is specific for ITP (Vanderheiden 1975). Vanderheiden (1969) reported high levels of ITP in the erythrocytes of two siblings and suggested that this resulted from homozygous deficiency of ITP-ase (MIM 147520). Support was provided by subsequent larger scale biochemical studies, which determined an allele frequency for the putative dysfunctional variant of ~0.05 in Caucasian populations (Holmes et al 1979;van Waeg et al 1988;Duley et al 1990).…”

mentioning

confidence: 99%

See 1 more Smart Citation

DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency

Cao¹,

Hegele²

2002

J Hum Genet

View full text Add to dashboard Cite

“…Subject GM1617 was a 29-year-old woman with complete ITP-ase deficiency originally reported by Vanderheiden (1969). DNA from five normal Caucasian control subjects was also sequenced.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency

Cao¹,

Hegele²

2002

J Hum Genet

View full text Add to dashboard Cite

“…In one population study, evidence was presented that a deficiency of ITPase was responsible for the high level of ITP found in 7 of Ͼ6,000 samples from mainly unrelated individuals. The frequency of heterozygosity for ITPase deficiency in Caucasian populations is estimated to be ϳ5% (6,(13)(14)(15). The gene coding for ITPase, ITPA, is located on the short arm of chromosome 20 (16).…”

mentioning

confidence: 99%

Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

Lin

McLennan

Kong

et al. 2001

Journal of Biological Chemistry

129

156

View full text Add to dashboard Cite

ITP and dITP exist in all cells. dITP is potentially mutagenic, and the levels of these nucleotides are controlled by inosine triphosphate pyrophosphatase (EC 3.6.1.19). Here we report the cloning, expression, and characterization of a 21.5-kDa human inosine triphosphate pyrophosphatase (hITPase), an enzyme whose activity has been reported in many animal tissues and studied in populations but whose protein sequence has not been determined before. At the optimal pH of 10.0, recombinant hITPase hydrolyzed ITP, dITP, and xanthosine 5-triphosphate to their respective monophosphates whereas activity with other nucleoside triphosphates was low. K m values for ITP, dITP, and xanthosine 5-triphosphate were 0.51, 0.31, and 0.57 mM, respectively, and k cat values were 580, 360, and 640 s ؊1 , respectively. A divalent cation was absolutely required for activity. The gene encoding the hITPase cDNA sequence was localized by radiation hybrid mapping to chromosome 20p in the interval D20S113-D20S97, the same interval in which the ITPA inosine triphosphatase gene was previously localized. A BLAST search revealed the existence of many similar sequences in organisms ranging from bacteria to mammals. The function of this ubiquitous protein family is proposed to be the elimination of minor potentially mutagenic or clastogenic purine nucleoside triphosphates from the cell.

show abstract

“…In addition to the studies of Mohrenweiser (1981) and Satoh et al (1983) which looked at an array of enzymes, variants have been reported for pyridoxine kinase (Chern and Beutler 1976), inosine triphosphatase (Vanderheiden 1969), phosphoglucose isomerase (Satoh and Mohrenweiser 1979), and glutamic oxaloacetic transaminase (Wurzinger and Mohrenweiser 1982). In all of these studies, the inheritance of a variant without alteration of the activity pattern was confirmed in family studies.…”

Section: Activity Variants and Null Allelesmentioning

confidence: 85%

The estimate of protein polymorphism in human populations: Lack of evidence for overestimation due to post-translational modification.

Fuerst

Ferrell

1985

The Japanese journal of genetics

View full text Add to dashboard Cite

New sensitive population screening procedures, such as isoelectric focusing, enzyme activity assays and the use of multiple electrophoretic conditions have uncovered considerable hidden variation at many structural loci. It has been suggested, however, that a significant portion of the newly identified variation is due to alleles at modifier genes which cause the post-translational modification of the structural gene product. Some investigators have questioned whether genetic variability assigned to structural loci in Drosophila has been greatly overestimated because of a failure to recognize the existence of such polymorphic modifier genes. Data from human populations has been reviewed for evidence of such genetically mediated posttranslational modification (GMPTM).Tnree genetic systems (glucose-6-phosphate dehydrogenase, alpha-1-antitrypsin and hemoglobin) are reviewed in detail. Each system is subject to non-genetic post-translational modification, but none of the data currently available indicates any role of GMPTM.Other data, including studies on null alleles, activity variants, population surveys and somatic cell hybrids is also reviewed. Again, no convincing evidence has been uncovered for the presence of GMPTM. It is concluded that the current estimates of polymorphism for enzymes and structural proteins in human populations have not been inflated due to the presence of polymorphism for modifier loci.

show abstract

Genetic studies of human erythrocyte inosine triphosphatase

Cited by 64 publications

References 6 publications

DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency

DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency

Cloning, Expression, and Characterization of a Human Inosine Triphosphate Pyrophosphatase Encoded by the ITPAGene

The estimate of protein polymorphism in human populations: Lack of evidence for overestimation due to post-translational modification.

Contact Info

Product

Resources

About