Glucose-6-phosphate 1-dehydrogenase (G6PD)
The protein contains 515 amino acids for an estimated molecular weight of 59257 Da.
Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. (updated: April 7, 2021)
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.
- 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
Carbohydrate metabolic process
Cellular response to oxidative stress
Cholesterol biosynthetic process
Cytokine production
Erythrocyte maturation
Glucose 6-phosphate metabolic process
Glucose metabolic process
Glutathione metabolic process
Lipid metabolic process
NADP metabolic process
NADPH regeneration
Negative regulation of cell growth involved in cardiac muscle cell development
Negative regulation of protein glutathionylation
Negative regulation of reactive oxygen species metabolic process
Oxidation-reduction process
Pathogenesis
Pentose biosynthetic process
Pentose-phosphate shunt
Pentose-phosphate shunt, oxidative branch
Positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
Regulation of neuron apoptotic process
Response to ethanol
Response to food
Response to iron(III) ion
Response to organic cyclic compound
Ribose phosphate biosynthetic process
Small molecule metabolic process
Substantia nigra development
The reference OMIM entry for this protein is 300908
Anemia, nonspherocytic hemolytic, due to g6pd deficiency
A number sign (#) is used with this entry because this form of nonspherocytic hemolyic anemia is caused by mutation in the G6PD gene (305900) on chromosome Xq28.
DESCRIPTION
G6PD deficiency is the most common genetic cause of chronic and drug-, food-, or infection-induced hemolytic anemia. G6PD catalyzes the first reaction in the pentose phosphate pathway, which is the only NADPH-generation process in mature red cells; therefore, defense against oxidative damage is dependent on G6PD. The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which in most patients is triggered by an exogenous agent, e.g., primaquine or fava beans (see 134700). Acute hemolysis is characterized by fatigue, back pain, anemia, and jaundice. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most G6PD-deficient patients are asymptomatic throughout their life. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria (see 611162) is endemic provided evidence that G6PD deficiency confers resistance against malaria (summary by Cappellini and Fiorelli, 2008).CLINICAL FEATURES
In primiquine-sensitive patients with hemolytic anemia, Carson et al. (1956) demonstrated an abnormality in the direct oxidation of glucose in red blood cells and deficiency of glucose-6-phosphate dehydrogenase. Cooper et al. (1972) and Gray et al. (1973) found that complete deficiency of G6PD produces not only nonspherocytic hemolytic anemia but also chronic granulomatous disease due to neutrophil dysfunction. The patient of Cooper et al. (1972) was a woman with complete leukocyte G6PD deficiency, partial deficiency in her red cells, and no family history of G6PD deficiency. Of the various possible explanations advanced by the authors, they preferred the suggestion that X-inactivation had affected the red cell and white cell series differently and that the patient indeed had G6PD deficiency. Gray et al. (1973) described 3 affected brothers. The mother showed an intermediate defect in leukocyte microbicidal and metabolic activity, as well as red and white blood cell mosaicism. In Saudi Arabia, Mallouh and Abu-Osba (1987) reviewed the G6PD status of all children aged 1 month to 14 years who were treated for meningitis, septicemia, osteomyelitis, or typhoid fever during a 9-year period. The observed frequency of G6PD deficiency was significantly higher than expected for the entire group, for females with both catalase-positive and catalase-negative infection, and for males with catalase-positive infections. Zinkham (1961) found that individuals with primaquine-sensitive erythrocytes had deficiency of G6PD activity in the lens. Orzalesi et al. (1981) found that G6PD deficiency was significantly more frequent among 210 male cataract patients in Sardinia than in 672 control subjects. This was particularly the case with presenile cataracts. Also in Sardinia, however, Meloni et al. (1990) found that patients with cataract had frequencies of G6PD deficiency no different from those in the general population. Ferraris et al. (1988) examined the hypothesis that there is a negative correlation between G6PD deficiency and hematologic malignancy. The frequency of G6PD deficiency in 481 Sardinian males with hematologic malignancies was not significantly different from that in a gro ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300908 was added.
Feb. 25, 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