Glutathione reductase, mitochondrial (GSR)

The protein contains 522 amino acids for an estimated molecular weight of 56257 Da.

 

Maintains high levels of reduced glutathione in the cytosol. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 97

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VariantDescription
dbSNP:rs8190955
dbSNP:rs8190976
dbSNP:rs8190976
dbSNP:rs8190997
dbSNP:rs8191004
dbSNP:rs2020916
HAGRD

The reference OMIM entry for this protein is 138300

Glutathione reductase; gsr glutathione reductase, hemolytic anemia due to deficiency of, in red cells, included

Long (1967) found in a black American a variant red cell GSR (EC 1.6.4.2) characterized by greater electrophoretic mobility and enzyme activity per unit of hemoglobin than the normal. Inheritance was autosomal codominant. Three homozygotes were identified. The relation to gout, suggested by Long (1967), is problematical. Long (1972) observed 2 variant forms of red cell GSR which appear to bind far more avidly than the common form of the enzyme. In cases of mosaic trisomy for chromosome 8, de la Chapelle et al. (1976) found elevated glutathione reductase activity, with other enzymes normal. George and Francke (1976) assigned the gene to the region 8p21-p23 by the gene dosage method. In an infant with terminal deletion of the short arm of chromosome 8, de la Chapelle et al. (1976) found low GSR activity. They concluded that the GSR locus is in the region 8pter-p21. Sinet et al. (1977) narrowed the assignment to 8p21. The GSR locus has also been assigned by somatic cell hybridization; it is one of the enzyme-markers for each chromosome (table 1 in Shows and Sakaguchi, 1980), useful for synteny mapping. Lohr and Waller (1962) observed a 'new' form of enzyme-deficiency hemolytic anemia in which glutathione reductase was deficient and glutathione (GSH) was low as a consequence. (This condition is apparently distinct from that described by Oort et al. (1961) in which GSH was also low, but glucose-6-phosphate dehydrogenase and glutathione reductase were normal.) Lohr (1963) observed 10 homozygotes and 5 heterozygotes in a family distribution consistent with autosomal recessive inheritance. Blume et al. (1968) studied a kindred with many persons who were demonstrably heterozygous by chemical test. Hampel et al. (1969) found a markedly increased frequency of chromosomal aberrations in a patient with pancytopenia and absent GSR-II band in the electropherogram. The mother was hematologically normal but had absent GSR-II band and a moderate increase in the frequency of chromosomal aberrations. Addition of chloramphenicol to the cultures increased the number of damaged chromosomes in both the mother and the son. Staal et al. (1969) described a variety of glutathione reductase anemia in which the variant enzyme had diminished affinity for flavin adenine dinucleotide (FAD). The patient's anemia was corrected by vitamin B2. Administration of flavin compounds to normal individuals or addition to hemolysates of most normal persons causes an increase in activity of GSR (Beutler, 1969). In a patient with systemic lupus erythematosus, Fajnholc et al. (1971) found red cell GSR deficiency which was correctable in vivo with riboflavin and in vitro with FAD. The same deficiency was found in the mother and some of her relatives (who were asymptomatic) but not in the father and his relatives. Enzyme kinetics were normal. These workers concluded that the defect was not in the apoenzyme. Loos et al. (1976) found virtually complete absence of GSR activity in the erythrocytes of 3 children of a consanguineous marriage and intermediate levels in the parents. Activity was not restored by FAD in vitro or riboflavin in vivo. Clinically the deficiency was manifested by favism in 1 child and by cataracts in 2. Reduced GSR was found in leukocytes, as well as evidence of impaired bactericidal capacity, but there was no history of repeated infections. Furthermore, Roos et al. (1979) found that chemotaxis, phagocytosis of opsonized S. aureus, and degranulation proceeded normall ... More on the omim web site

Subscribe to this protein entry history

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 138300 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed