Ribose-phosphate pyrophosphokinase 1 (PRPS1)
The protein contains 318 amino acids for an estimated molecular weight of 34834 Da.
Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis. (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
5-phosphoribose 1-diphosphate biosynthetic process
AMP biosynthetic process
Animal organ regeneration
Carbohydrate metabolic process
Hypoxanthine biosynthetic process
Nervous system development
Nucleoside metabolic process
Nucleotide biosynthetic process
Pathogenesis
Purine nucleobase metabolic process
Purine nucleotide biosynthetic process
Pyrimidine nucleotide biosynthetic process
Ribonucleoside monophosphate biosynthetic process
Small molecule metabolic process
Urate biosynthetic process
The reference OMIM entry for this protein is 300661
Phosphoribosylpyrophosphate synthetase superactivity
Prps1 superactivity gout, prps-related, included
A number sign (#) is used with this entry because the phenotype is caused by mutations in the gene encoding phosphoribosylpyrophosphate synthetase I (PRPS1; 311850) that result in increased enzyme activity. X-linked recessive Charcot-Marie-Tooth disease-5 (
CMT
X5; 311070) is an allelic disorder resulting from decreased enzyme activity. Affected individuals have neurologic symptoms, including sensorineural deafness. Another allelic disorder, Arts syndrome (301835), results from loss of PRPS1 activity and has a severe neurologic phenotype including mental retardation, early-onset hypotonia, and susceptibility to infections.DESCRIPTION
Phosphoribosylpyrophosphate synthetase I superactivity is an X-linked inborn error of metabolism in which increased enzyme activity is associated with hyperuricemia and gout. Some affected individuals have neurodevelopmental abnormalities, particularly sensorineural deafness (Becker et al., 1988; Roessler et al., 1993). Although different kinetic defects affecting the PRPS1 enzyme have been identified in this disorder, the common pathway involves increased synthesis of phosphoribosylpyrophosphate (PRPP), which leads to increased uric acid and purine production (Becker, 2001).CLINICAL FEATURES
Sperling et al. (1972, 1973) and Zoref et al. (1975, 1977) described a familial disorder characterized by early-adult onset of excessive purine production, gout, and uric acid urolithiasis associated with hyperuricemia and hyperuricosuria. The PRPS1 enzyme activity was described as 'superactive,' showing increased de novo synthesis of purine nucleotides. PRPS1 activity in red cells and cultured skin fibroblasts was resistant to feedback inhibition by guanosine diphosphate (GDP) and adenosine diphosphate (ADP). Fibroblast cultures were homogeneous for the mutant enzyme in affected males, whereas unaffected females showed mutant and normal activity. The pattern of inheritance was X-linked recessive. Becker et al. (1980) provided follow-up studies of a family reported by Nyhan et al. (1969) in which a boy had hyperuricemia, mental retardation, and sensorineural deafness from infancy associated with PRPS1 superactivity. His affected mother had gout, uric acid urolithiasis, and significant hearing loss. Fibroblast studies of this patient and his mother indicated that the mutant enzyme had both regulatory and catalytic defects. The enzyme showed 4- to 5-fold greater than normal resistance to feedback inhibition and, in addition, increased maximal velocity of the enzyme reaction. The son was hemizygous, and his mother heterozygous, for the defect. Simmonds et al. (1982) reported a 3-year-old boy with hypotonia, locomotor delay, and high frequency hearing loss associated with purine hyperactivity. The same disorder was probably present in 2 brothers who died in early childhood. The mother also showed hyperuricemia, purine overproduction, and sensorineural deafness from infancy. Severe depletion of red cell nicotinamide adenine dinucleotide (NAD) and GTP appeared to be associated with the neurologic abnormalities. Simmonds et al. (1982) referred to the report of Rosenberg et al. (1970) in which 5 family members had ataxia, deafness, hyperuricemia, and renal insufficiency. Serum urate levels were elevated in other members of the kindred who did not have renal insufficiency, indicating that the hyperuricemia was not secondary to renal disease. Red cell hypoxanthine-guanine phosphoribosyltransferas ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300661 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed