Inosine triphosphate pyrophosphatase (ITPA)
The protein contains 194 amino acids for an estimated molecular weight of 21446 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
Biological Process
Chromosome organization
Deoxyribonucleoside triphosphate catabolic process
ITP catabolic process
Nucleobase-containing small molecule metabolic process
Nucleoside triphosphate catabolic process
Purine nucleotide catabolic process
Small molecule metabolic process
Cellular Component
Cytoplasm
Cytosol
Intracellular membrane-bounded organelle
Nuclear body
Nucleoplasm
The reference OMIM entry for this protein is 147520
Inosine triphosphatase; itpa
Inosine triphosphate pyrophosphohydrolase
DESCRIPTION
Inosine triphosphate pyrophosphohydrolase (ITPase; EC 3.6.1.19) catalyzes the pyrophosphohydrolysis of inosine triphosphate (ITP) to inosine monophosphate (IMP) (Sumi et al., 2002).CLONING
Lin et al. (2001) isolated and expressed a full-length cDNA clone encoding human ITPase. The 1,085-basepair cDNA contained an open reading frame of 585 nucleotides encoding a protein of 194 amino acids. Lin et al. (2001) showed that ITPase is present not only in red blood cells, but also in many tissues.GENE STRUCTURE
Sumi et al. (2002) showed that the ITPA gene contains 8 exons.MAPPING
From cell hybrid studies, the ITPA structural gene was shown to be on chromosome 20 (Meera Khan et al., 1976; Hopkinson et al., 1976). Gene dosage studies of adenosine deaminase (ADA; 608958) and ITPA provided corroboration of partial trisomy 20 diagnosed cytogenetically (Rudd et al., 1979). The human ITPA gene is on 20p; the gene for ADA, a functionally related enzyme, is on 20q (Mohandas et al., 1980). Using linkage methods, Taylor et al. (1987) assigned the mouse Itp locus to chromosome 2.GENE FUNCTION
Sumi et al. (2002) stated that the putative role of ITPase is to recycle purines trapped in the form of ITP and to protect the cell from the accumulation of 'rogue' nucleotides such as ITP, dITP, or xanthosine triphosphate (XTP) that may be incorporated into RNA and DNA.MOLECULAR GENETICS
Harris et al. (1974) found no genetic variants at the inosine triphosphatase locus by electrophoretic means. Sumi et al. (2002) identified 2 mutations in the ITPA gene (147520.0001, 147520.0002) associated with deficient ITPase enzyme activity (613850). Sumi et al. (2002) suggested that the possibility of thiopurine drug toxicity consequent to ITPase deficiency warrants further investigation. Chronic hepatitis C virus infection is treated with a combination of pegylated interferon-alpha (147660) and ribavirin. One of the most important side effects is ribavirin-induced hemolytic anemia, which affects most patients and is severe enough to require dose modification in up to 15% of patients. Fellay et al. (2010) showed that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against hemolytic anemia in hepatitis C-infected patients receiving ribavirin. The association between the ITPA gene variants with protection against anemia was identified by an association between the SNP dbSNP rs6051702 with a genomewide P value of 1.1 x 10(-45) among European Americans. This SNP was in linkage disequilibrium with 2 less common alleles within ITPA, a P32T mutation (dbSNP rs1127354, 147520.0001) and a splice site variant (dbSNP rs7270101, 147520.0002). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 147520 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed