Glutathione S-transferase theta-1 (GSTT1)
The protein contains 240 amino acids for an estimated molecular weight of 27335 Da.
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chloride and 4-nitrophenethyl bromide. Displays glutathione peroxidase activity with cumene hydroperoxide. (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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs2266635 | |
| dbSNP:rs2266633 | |
| dbSNP:rs2266637 | |
| dbSNP:rs2234953 |
The reference OMIM entry for this protein is 600436
Glutathione s-transferase, theta-1; gstt1
DESCRIPTION
Glutathione S-transferases catalyze the conjugation of glutathione to a wide range of potential toxins as the first step in detoxification. The GSTs form a superfamily whose dimeric proteins have been placed into several multigene families. For background information on GSTs, see 138350.CLONING
For a long time the glutathione S-transferases of the theta class were largely overlooked because of their low activity with the model substrate 1-chloro-2,4-dinitrobenzene (CDNB) and their failure to bind to immobilized glutathione affinity matrices. Pemble et al. (1994) reported the cDNA cloning of a human theta-class GST, termed GSTT1. The deduced 239-amino acid GSTT1 protein shares 80% sequence identity with the rat homolog.MAPPING
By in situ hybridization studies, Webb et al. (1996) mapped the GSTT1 gene to 22q11.2, the same band where GSTT2 (600437) is localized.MOLECULAR GENETICS
In humans, glutathione-dependent conjugation of halomethane is polymorphic, with 60% of the population classed as conjugators and 40% as nonconjugators. From PCR and Southern blot analyses, Pemble et al. (1994) showed that the GSTT1 gene was absent from 38% of the population. The presence or absence of the gene was coincident with the conjugator (GSTT1+) and nonconjugator (GSTT1-) phenotypes, respectively. The GSTT1+ phenotype can catalyze the glutathione conjugation of dichloromethane, a metabolic pathway that had been shown to be mutagenic in Salmonella typhimurium mutagenicity tester strains and was believed to be responsible for the carcinogenicity of dichloromethane in the mouse. In humans, the GSTT1 enzyme is found in the erythrocyte and this may act as a detoxification sink. Thus, Pemble et al. (1994) stated that characterization of the GSTT1 polymorphism would enable a more accurate assessment of human health risk from synthetic halomethanes and other industrial chemicals. Chen et al. (1996) compared the frequency of the GSTT1 null genotype in 96 patients with myelodysplastic syndromes (MDS) and 201 cancer-free controls of similar age, race, and sex. The frequency of the GSTT1 null genotype was 46% among MDS cases and 16% among controls. Inheritance of the GSTT1 null genotype was calculated to confer a 4.3-fold increased risk of MDS. The GSTM1 null genotype (138350) was not associated with an increased risk of MDS. The authors suggested that the mechanism of the association might be decreased detoxification of environmental or endogenous carcinogens. Patients with reduced ability to metabolize environmental carcinogens or toxins may be at risk of developing aplastic anemia. GST has been implicated in detoxifying mutagenic electrophilic compounds. Lee et al. (2001) investigated whether homozygous deletions of GSTM1 and GSTT1 affect the likelihood of developing aplastic anemia. They found that the incidence of GSTM1 and GSTT1 gene deletions was significantly higher for aplastic anemia patients than for healthy controls (odds ratio = 3.1, P = 0.01, and odds ratio = 3.1, P = 0.004, respectively). Among the aplastic anemia patients, 17.5% had chromosomal abnormalities at the time of diagnosis, and all aplastic anemia patients with chromosomal abnormalities showed GSTT1 gene deletions. Chen et al. (1996) described a method for simultaneous characterization of GSTM1 and GSTT1 and studied the genotypes in whites and blacks. The frequency of the null genotype for GSTM1 (GSTM1-) was higher in whites and that ... 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 600436 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed