Glutathione peroxidase 1 (GPX1)
The protein contains 203 amino acids for an estimated molecular weight of 22088 Da.
Protects the hemoglobin in erythrocytes from oxidative breakdown. In platelets, plays a crucial role of glutathione peroxidase in the arachidonic acid metabolism (PubMed:11115402). (updated: June 17, 2020)
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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs8179169 | |
| dbSNP:rs6446261 | |
| dbSNP:rs1050450 |
Biological Process
Aging
Angiogenesis involved in wound healing
Arachidonic acid metabolic process
Biological process involved in interaction with symbiont
Blood vessel endothelial cell migration
Cell redox homeostasis
Cellular response to oxidative stress
Endothelial cell development
Fat cell differentiation
Glutathione metabolic process
Heart contraction
Hydrogen peroxide catabolic process
Intrinsic apoptotic signaling pathway in response to oxidative stress
Lipoxygenase pathway
Myoblast proliferation
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Negative regulation of inflammatory response to antigenic stimulus
Negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
Negative regulation of release of cytochrome c from mitochondria
Nucleobase-containing small molecule metabolic process
Positive regulation of protein kinase B signaling
Positive regulation of supramolecular fiber organization
Protein oxidation
Purine nucleobase metabolic process
Purine nucleotide catabolic process
Regulation of gene expression, epigenetic
Regulation of mammary gland epithelial cell proliferation
Regulation of neuron apoptotic process
Regulation of proteasomal protein catabolic process
Response to estradiol
Response to folic acid
Response to gamma radiation
Response to glucose
Response to hydrogen peroxide
Response to hydroperoxide
Response to lipid hydroperoxide
Response to nicotine
Response to reactive oxygen species
Response to selenium ion
Response to symbiotic bacterium
Response to toxic substance
Response to xenobiotic stimulus
Sensory perception of sound
Skeletal muscle fiber development
Skeletal muscle tissue regeneration
Small molecule metabolic process
Temperature homeostasis
Triglyceride metabolic process
UV protection
Vasodilation
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Mitochondrial matrix
Mitochondrion
Nucleus
Obsolete cell
The reference OMIM entry for this protein is 138320
Glutathione peroxidase; gpx1
DESCRIPTION
Glutathione peroxidase (EC 1.11.1.9) catalyzes the reduction of organic hydroperoxides and hydrogen peroxide by glutathione and thereby protects against oxidative damage (summary by Cohen et al., 1989).CLONING
Paglia and Valentine (1967) characterized red cell glutathione peroxidase. Sukenaga et al. (1987) presented the sequence of GPX cDNA. GPX is one of only a few proteins known in higher vertebrates to contain selenocysteine. This unusual amino acid occurs at the active site of GPX and is coded by the nonsense (stop) codon TGA. Sequence analysis of cDNA clones confirmed previous findings that the unusual amino acid selenocysteine is encoded by the opal terminator codon UGA (Le Beau, 1989). (Note that TGA = UGA; they represent the cDNA and mRNA code, respectively.) There appears to be a selenocysteyl-tRNA that donates selenocysteine to the growing polypeptide chain of GPX, and therefore, selenocysteine becomes the twenty-first naturally occurring amino acid. A tRNA molecule that carries selenocysteine has its own translating factor that delivers it to the translating ribosome (Bock et al., 1991). Bacterial formate dehydrogenase also contains selenocysteine.MAPPING
Wijnen et al. (1978) presented evidence that GPX1 is on chromosome 3. Johannsmann et al. (1979) concluded that the GPX locus is on 3p. In situ hybridization localized the gene to 3p13-q12 (Johannsmann et al., 1981). McBride et al. (1988) used a cDNA probe to study DNAs isolated from human-rodent somatic cell hybrids. A 609-bp probe containing the entire coding region hybridized to human chromosomes 3, 21, and Xp. An intronic probe detected only the gene on chromosome 3. The sequences on chromosomes X and 21 showed equal conservation of the 3-prime untranslated and coding sequences but did not contain introns, suggesting that they represent processed pseudogenes. By fluorescence in situ hybridization and PCR analysis, Kiss et al. (1997) mapped the GPX1 gene to 3p21.3. Their results were compatible with the existence of a pseudogene of GPX1 on 3q11-q12 (Chada et al., 1990). Mehdizadeh et al. (1996) mapped the Gpx1 gene to mouse chromosome 9 in a region of known conserved homology between mouse chromosome 9 and human chromosome 3.GENE FUNCTION
Using a radioimmunoassay for GSHPx, Takahashi et al. (1986) showed that there is a direct relationship between GPX enzyme activity and enzyme protein concentration. Thus, selenium is necessary for the synthesis of protein. Selenium deficiency (see 614164) results in a decrease not only in glutathione peroxidase activity but also in GSHPx protein. Only erythrocytes formed in the presence of selenium contain GSHPx activity. The possibility of confusing genetic and environmental factors is indicated. Takahashi et al. (1987) observed a selenium-dependent GPX in human plasma that is distinct from the one found in erythrocytes.MOLECULAR GENETICS
By electrophoretic means, Beutler and West (1974) demonstrated polymorphism of red cell glutathione peroxidase in Afro-Americans. An electrophoretic polymorphism of glutathione peroxidase was described by Beutler et al. (1974). Beutler and Matsumoto (1975) found that persons of Jewish ancestry and others of Mediterranean origin have a decrease in red cell GPX activity, but not of leukocyte or fibroblast activity. Oriental populations showed a significantly lower scatter in red cell enzyme levels in comparison with Occidental populati ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 138320 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed