Hypoxanthine-guanine phosphoribosyltransferase (HPRT1)
The protein contains 218 amino acids for an estimated molecular weight of 24579 Da.
Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway. (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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
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Biological Process
Adenine salvage
Central nervous system neuron development
Cerebral cortex neuron differentiation
Cytolysis
Dendrite morphogenesis
Dopamine metabolic process
GMP catabolic process
GMP salvage
Grooming behavior
Guanine salvage
Hypoxanthine metabolic process
Hypoxanthine salvage
IMP metabolic process
IMP salvage
Locomotory behavior
Lymphocyte proliferation
Nucleobase-containing small molecule metabolic process
Positive regulation of dopamine metabolic process
Protein homotetramerization
Purine nucleobase metabolic process
Purine nucleotide biosynthetic process
Purine ribonucleoside salvage
Purine-containing compound salvage
Response to amphetamine
Small molecule metabolic process
Striatum development
T cell mediated cytotoxicity
The reference OMIM entry for this protein is 300322
Lesch-nyhan syndrome; lns
Hypoxanthine guanine phosphoribosyltransferase 1 deficiency
Hprt1 deficiency
Hprt deficiency
Hprt deficiency, complete hprt deficiency, neurologic variant, included
Lesch-nyhan syndrome, neurologic variant, include
A number sign (#) is used with this entry because Lesch-Nyhan syndrome is caused by mutation in the HPRT gene (308000) encoding hypoxanthine guanine phosphoribosyltransferase.
CLINICAL FEATURES
The features of the Lesch-Nyhan syndrome are mental retardation, spastic cerebral palsy, choreoathetosis, uric acid urinary stones, and self-destructive biting of fingers and lips. Megaloblastic anemia has been found by some (van der Zee et al., 1968). Virtually complete deficiency of HPRT residual activity (less than 1.5%) is associated with the Lesch-Nyhan syndrome, whereas partial deficiency (at least 8%) is associated with the Kelley-Seegmiller syndrome (300323). LNS is characterized by abnormal metabolic and neurologic manifestations. In contrast, Kelley-Seegmiller syndrome is usually associated only with the clinical manifestations of excessive purine production. Renal stones, uric acid nephropathy, and renal obstruction are often the presenting symptoms of Kelley-Seegmiller syndrome, but rarely of LNS. After puberty, the hyperuricemia in Kelley-Seegmiller syndrome may cause gout. A third group of patients, with 1.5 to 8% of HPRT activity, is associated with a neurologic variant of LNS, with uric acid overproduction and neurologic disability that varies from minor clumsiness to debilitating extrapyramidal and pyramidal motor dysfunction (Jinnah and Friedmann, 2001). Bakay et al. (1979) restudied a patient with HPRT deficiency, choreoathetosis, spasticity, dysarthria, and hyperuricemia, but normal intelligence and no self-mutilation. (A maternal uncle had been identically affected.) Although HPRT deficiency seemed to be complete, cultured fibroblasts had some capacity for metabolism of hypoxanthine and guanine. Page et al. (1987) described 2 brothers and 2 of their maternal uncles who had HPRT deficiency as the cause of mild mental retardation, spastic gait, and pyramidal tract sign. They were, furthermore, short of stature with proximally placed thumbs and fifth finger clinodactyly. Activity of the enzyme was virtually zero in lysates of red cells or hair roots, but in intact fibroblasts the level of activity was 7.5% of normal. Kinetic studies also demonstrated differences. A sister of the brothers was, by enzyme assay, heterozygous. One of the affected uncles had advanced tophaceous gout by age 32 years. - Clinical Variability Hladnik et al. (2008) reported a family in which 5 individuals carrying the same splice site mutation in the HPRT gene showed marked phenotypic variability resulting from HPRT deficiency. One patient had classic Lesch-Nyhan syndrome with delayed development, spasticity, dystonia, and self-injurious behavior. Two patients had an intermediate phenotype with mild cognitive and learning difficulties, dystonia, and increased uric acid, but no self-injurious behavior, and 2 had mild spasticity, gout, and normal IQ. Hladnik et al. (2008) postulated that each individual had various expression of the mutant and wildtype transcript, and emphasized that individuals with the same genotype may not necessarily have the identical phenotype. Sarafoglou et al. (2010) reported a 3-generation family in which 3 individuals carrying the same missense mutation in the HPRT1 gene showed phenotypic variability. The proband presented at age 14.5 months with increased uric acid levels and later showed mildly delayed development. His cousin was diagnosed at age 26 months, and had mild generalized hypotonia, delayed motor development ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300322 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed