ATP-dependent 6-phosphofructokinase, muscle type (PFKM)
The protein contains 780 amino acids for an estimated molecular weight of 85183 Da.
Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis. (updated: March 4, 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.
- 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.
- 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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| Variant | Description |
|---|---|
| GSD7 | |
| GSD7 | |
| GSD7; Italian | |
| dbSNP:rs2228500 | |
| GSD7; Italian | |
| GSD7 | |
| GSD7 | |
| GSD7 | |
| GSD7; Italian | |
| GSD7 | |
| dbSNP:rs41291971 |
Biological Process
Canonical glycolysis
Carbohydrate metabolic process
Carbohydrate phosphorylation
Fructose 1,6-bisphosphate metabolic process
Fructose 6-phosphate metabolic process
Glucose catabolic process
Glucose homeostasis
Glucose metabolic process
Glycogen catabolic process
Glycolysis from storage polysaccharide through glucose-1-phosphate
Glycolytic process
Glycolytic process through fructose-6-phosphate
Muscle cell cellular homeostasis
Pathogenesis
Positive regulation of insulin secretion
Positive regulation of transcription by RNA polymerase II
Protein complex oligomerization
Protein homotetramerization
Small molecule metabolic process
The reference OMIM entry for this protein is 232800
Glycogen storage disease vii; gsd7
Gsd vii
Muscle phosphofructokinase deficiency
Pfkm deficiency
Tarui disease
A number sign (#) is used with this entry because glycogen storage disease VII (GSD7) is caused by homozygous or compound heterozygous mutation in the PFKM gene (610681), which encodes muscle phosphofructokinase, on chromosome 12q13.
DESCRIPTION
Glycogen storage disease VII is an autosomal recessive metabolic disorder characterized clinically by exercise intolerance, muscle cramping, exertional myopathy, and compensated hemolysis. Myoglobinuria may also occur. The deficiency of the muscle isoform of PFK results in a total and partial loss of muscle and red cell PFK activity, respectively. Raben and Sherman (1995) noted that not all patients with GSD VII seek medical care because in some cases it is a relatively mild disorder.CLINICAL FEATURES
Tarui et al. (1965) first described this disorder in 3 affected Japanese sibs, a 20-year-old female and 23- and 27-year-old males. The parents were first cousins. The affected sibs complained of easy fatigability and inability to keep pace with other persons. Physical examination revealed marked weakness and stiffness in muscle groups subjected to vigorous or prolonged exertion. Venous lactate failed to rise with the ischemic exercise test; 1 sib had myoglobinuria following the test. PFK activity was entirely absent in muscle and about half normal in erythrocytes. Layzer et al. (1967) reported an 18-year-old male with muscle PFK deficiency and red cell hemolysis. The erythrocytes of both unaffected parents showed partial enzyme activity. Layzer et al. (1967) suggested that red cell PFK is composed of 2 types of subunits, 1 of which is the sole subunit present in muscle PFK. The authors concluded that the genetic defect likely involves a subunit common to both the muscle and the red cell enzyme, and furthermore postulated autosomal recessive inheritance. Satoyoshi and Kowa (1967) described myopathy in 2 affected brothers. Family history revealed that myopathy was also present in a sister, their mother, and a son of 1 sister. Onset was about age 35 years with delayed muscle pain and stiffness on exertion, but absence of contracture or weakness on ischemic exercise. Phosphofructokinase activity was about 40% of normal in skeletal muscle. Oral ingestion of fructose relieved the symptoms. Satoyoshi and Kowa (1967) suggested the possible role of an inhibitor in the disease process. Waterbury and Frenkel (1972) found an intermediate level (60% of normal) of the PFK enzyme in the red cells of a physician with chronic compensated hemolysis and in his mother and grandmother who lacked evidence of hemolysis. The proband had 9% reticulocytes. PFK of the proband showed markedly increased lability on in vitro studies. The absence of muscle disease was atypical of the usual phenotype associated with type VII glycogen storage disease. Vora et al. (1980) studied a patient with the rare Tarui disease, in which myopathy and hemolysis are associated with PFK deficiency. The proband was a 31-year-old man who suffered from muscular weakness and myoglobinuria on exertion. He showed mild erythrocytosis despite laboratory evidence of hemolysis. His red cell PFK was exclusively of the L (liver) type (PFKL; 171860). Decreased production of 2,3-DPG was held responsible for the paradoxic erythrocytosis. Tani et al. (1983) studied 2 unrelated Japanese kindreds with PFKM deficiency associated with congenital nonspherocytic hemolytic anemia and mild myopathy. Both probands had jaundice, gallstones, and slig ... 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 232800 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed