Phosphoglycerate kinase 1 (PGK1)
The protein contains 417 amino acids for an estimated molecular weight of 44615 Da.
Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). May play a role in sperm motility (PubMed:26677959). (updated: Oct. 16, 2019)
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.
(right-click above to access to more options from the contextual menu)
Biological Process
Canonical glycolysis
Carbohydrate metabolic process
Cellular response to hypoxia
Epithelial cell differentiation
Gluconeogenesis
Glucose metabolic process
Glycolytic process
Modulation by symbiont of host process
Negative regulation of angiogenesis
Pathogenesis
Phosphorylation
Plasminogen activation
Positive regulation of oxidative phosphorylation
Small molecule metabolic process
The reference OMIM entry for this protein is 300653
Phosphoglycerate kinase 1 deficiency
Pgk1 deficiency
A number sign (#) is used with this entry because phosphoglycerate kinase-1 deficiency is caused by mutation in the PGK1 gene (311800).
DESCRIPTION
Phosphoglycerate kinase-1 deficiency is an X-linked recessive condition with a highly variable clinical phenotype that includes hemolytic anemia, myopathy, and neurologic involvement. Patients can express 1, 2, or all 3 of these manifestations (Shirakawa et al., 2006).CLINICAL FEATURES
Kraus et al. (1968) attributed lifelong anemia in a 63-year-old Caucasian woman to deficiency of red cell phosphoglycerate kinase. Although no relatives were available for study, the proband's mother and 2 of her sibs had a history of anemia. Valentine et al. (1969) found hemolytic anemia with deficient red and white cell phosphoglycerate kinase in a large Chinese kindred. Mild hemolysis was present in presumed heterozygotes. Guis et al. (1987) reported a boy with hemolytic anemia but no neuromuscular manifestations who was found to have a PGK variant termed 'San Francisco.' The anemia was severe and partially transfusion dependent. Guis et al. (1987) suggested that unusual stability of the mutant enzyme and a continuing ability to synthesize at least limited amounts of enzyme had protected nonerythroid tissues. In contrast, mature red cells, lacking the ability to synthesize new proteins, had a severely compromised life span. Rosa et al. (1982) reported a man with episodes of rhabdomyolysis and acute renal failure who did not have hemolysis. He had a severe deficiency of PGK in muscle, white blood cells, red blood cells, and platelets. His mother and 2 daughters had a partial enzyme defect in red blood cells, suggesting X-linked recessive transmission. DiMauro et al. (1983) reported a 14-year-old boy with recurrent myoglobinuria and renal failure after intense exercise. Muscle PGK activity was 5% of normal values in the patient and was decreased in his mother but normal in his father. Tonin et al. (1993) reported a 37-year-old man with exercise intolerance, myalgia, recurrent myoglobinuria, and retinitis pigmentosa who had decreased PGK activity. Sugie et al. (1994) demonstrated PGK deficiency in 3 unrelated men who presented with myoglobinuria. All 3 were mentally retarded, and 2 had epilepsy. The patient who did not have epilepsy was the only one of the 3 who showed any hemolytic anemia. Sugie et al. (1994) noted that organ-specific isozymes or posttranslational modification are not the explanation for the variable involvement of hematopoietic, muscle and nervous tissue since enzymes derived from different tissues in the same individual do not differ in physical and biochemical characteristics. The variable clinical features of the disease were thought to be the consequence of the unique biochemical properties of the individual PGK mutants. Noel et al. (2005) reported 2 unrelated boys of Spanish origin with PGK1 deficiency. At the age of 2 years, the first child was hospitalized for a febrile episode associated with severe anemia and jaundice, for which exchange transfusion was given. Subsequently, several similar hemolytic crises occurred, mainly due to viral infections, and exchange transfusion was required on 2 occasions. Due to the persistence of the microcytosis, a molecular study for thalassemia was performed, leading to the secondary diagnosis of heterozygosity for the alpha(-3.7) mutation. At 7 years of age the hemolytic crises were associated with a progressive neurologic imp ... More on the omim web site
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: 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 300653 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed