ATP-dependent 6-phosphofructokinase, liver type (PFKL)
The protein contains 780 amino acids for an estimated molecular weight of 85018 Da.
Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:22923583). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway (By similarity). (updated: April 25, 2018)
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 |
|---|---|
| empty | |
| dbSNP:rs755851304 | |
| dbSNP:rs1057037 |
Biological Process
Canonical glycolysis
Carbohydrate metabolic process
Carbohydrate phosphorylation
Fructose 1,6-bisphosphate metabolic process
Fructose 6-phosphate metabolic process
Glucose catabolic process
Glucose metabolic process
Glycolytic process
Negative regulation of insulin secretion
Neutrophil degranulation
Pathogenesis
Protein complex oligomerization
Protein homotetramerization
Response to glucose
Small molecule metabolic process
The reference OMIM entry for this protein is 171860
Phosphofructokinase, liver type; pfkl
Pfk, liver type
DESCRIPTION
The PFKL gene encodes the liver isoform of phosphofructokinase (PFK) (ATP:D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11). PFK catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate and is a key regulatory enzyme in glycolysis. Mammalian PFK is a tetramer made up of various combinations of 3 subunits: muscle (PFKM; 610681), liver (PFKL), and platelet (PFKP; 171840), the genes for which are located on chromosomes 12q13, 21q22, and 10p, respectively. The composition of the tetramers differs according to the tissue type. Muscle and liver PFK are a homotetramers of 4M and 4L subunits, respectively. Erythrocytes contain both L and M subunits, which randomly tetramerize to form M4, L4, M3L, M2L2, and ML3 hybrid forms of the holoenzyme (Vora et al., 1980; Raben and Sherman, 1995).CLONING
Levanon et al. (1986) isolated partial cDNA clones corresponding to the human PFKL gene. Levanon et al. (1987) isolated overlapping cDNA clones corresponding to the full-length human PFKL gene from a human fibroblast cDNA library. The deduced protein has a molecular mass of 80 kD and the PFKL mRNA is approximately 3.5 kb. Levanon et al. (1987) noted that the L-type isoform predominates in organs with active gluconeogenesis, such as liver and kidney. Levanon et al. (1989) stated that the human PFKL protein contains 779 amino acids and shares approximately 90% and 68% homology with mouse Pfkl and human PFKM, respectively. Gehnrich et al. (1988) described the isolation and nucleotide sequencing of mouse Pfkl cDNA and presented evidence of hormonal and nutritional regulation of its expression.GENE STRUCTURE
Elson et al. (1990) determined that the PFKL gene contains 22 exons and spans approximately 28 kb.GENE FUNCTION
Yi et al. (2012) demonstrated that the dynamic posttranslational modification of proteins by O-linked beta-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at ser529 of phosphofructokinase-1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at ser529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo.MAPPING
On the basis of apparent dosage effect in trisomy 21 (Down syndrome; 190685), Baikie et al. (1965) concluded that a gene for so-called 'red cell' phosphofructokinase was on chromosome 21. In support of these findings, Pantelakis et al. (1970) reported a 74% and 41% increase of erythrocyte PFK activity in newborn and older children with Down syndrome, respectively, suggesting localization of a gene to chromosome 21. By somatic cell hybridization, Vora and Francke (1981) mapped the PFKL gene to chromosome 21. The authors also found that the mean red cell PFK was elevated in persons with Down syndrome. By study of dosage effects in cases of partial monosomy or partial trisomy of chromosome 21, Chadefaux et al. (1984) concluded that the liver-type PFK is located at 21q21-qter. This mapping was consistent with the regional assignment to 21q22 by Cox et al. (1984). Van Keuren et al. (1986) mapped the PFKL gene to 21q22.3 by somatic cell hamster-human hybridization. Levanon et al. (1986) confirmed the assignment of PFKL to chromosome 21 by demonstrating hybridizati ... More on the omim web site
April 27, 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 171860 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed