Glutathione synthetase (GSS)
The protein contains 474 amino acids for an estimated molecular weight of 52385 Da.
No function (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.
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Biological Process
Aging
Cellular amino acid metabolic process
Glutathione biosynthetic process
Glutathione derivative biosynthetic process
Nervous system development
Response to amino acid
Response to cadmium ion
Response to nutrient levels
Response to oxidative stress
Response to tumor necrosis factor
Response to xenobiotic stimulus
Small molecule metabolic process
Xenobiotic metabolic process
The reference OMIM entry for this protein is 231900
Glutathione synthetase deficiency of erythrocytes, hemolytic anemia due to; gssde
A number sign (#) is used with this entry because of evidence hemolytic anemia due to glutathione synthetase deficiency of erythrocytes (GSSDE) can be caused by homozygous mutation in the gene encoding glutathione synthetase (GSS; 601002), on chromosome 20q11. The same gene is mutant in 5-oxoprolinuria (266130).
DESCRIPTION
Two forms of glutathione synthetase deficiency have been described; a mild form, referred to as glutathione synthetase deficiency of erythrocytes, causing hemolytic anemia, and a more severe form causing 5-oxoprolinuria with secondary neurologic involvement (266130).CLINICAL FEATURES
Mohler et al. (1970) described a man of Scottish extraction with hemolytic anemia due to deficiency of glutathione synthetase. Four children of the proband, 1 of 3 of his sibs, and both parents had intermediate levels of enzyme. Presumably, the families of Oort et al. (1961) and of Boivin et al. (1966) had the same condition. In the family reported by Prins et al. (1966), 3 of 12 sibs from second-cousin parents had absence of glutathione in the erythrocytes. The clinical picture was that of nonspherocytic hemolytic anemia. Glyoxalase activity, which is dependent on glutathione as a cofactor, was also deficient. Other enzymes were increased, presumably due to the younger average age of erythrocytes. In a later report on the kindred, 5 cases in 2 sibships, with all 4 parents traced to a common ancestral couple, were described. Glutathione (gamma-glutamyl-cysteinyl-glycine) was less than 10% of normal in presumed homozygotes. Spielberg et al. (1978) showed an enzymatic difference between 5-oxoprolinuria (pyroglutamic aciduria) and isolated hemolytic anemia due to glutathione synthetase deficiency. In the former all cell types examined have grossly deficient enzyme activity and glutathione content. In contrast, in the nonoxoprolinuric variant, red cells have reduced enzyme and glutathione, but nucleated cells are normal. The enzyme from the latter type is unstable in vitro and shows shortened survival in intact erythrocytes. Nucleated cells are apparently able to maintain sufficient enzyme activity and glutathione content to suppress overproduction of 5-oxoproline. Beutler et al. (1986) described 2 sibs with hemolytic anemia. Their red cells lacked GSH and were severely deficient in GSH-S. No neurologic abnormalities or 5-oxoprolinuria were present. A concurrent glutathione-S-transferase (GST; see 138350) deficiency was also found in red cells. The GSH-S activity was one-half normal in the parents, but GST was normal, indicating that GSH-S deficiency is the primary defect. Glutathione stabilizes GST.CLINICAL MANAGEMENT
Ristoff et al. (2001) studied 28 patients with GSS deficiency, which they classified into 3 types based on severity of clinical signs: mild (hemolytic anemia only), moderate (neonatal acidosis), and severe (neurologic involvement). They concluded that early supplementation with vitamins C and E may improve the long-term clinical outcome of these patients.MAPPING
By analysis of somatic cell hybrids and FISH, Webb et al. (1995) mapped the GSS gene to chromosome 20q11.2.MOLECULAR GENETICS
In the patient with GSS deficiency reported by Mohler et al. (1970), Shi et al. (1996) identified a homozygous missense mutation in the GSS gene (601002.0007). ... 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 231900 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed