Alternative titles; symbols
HGNC Approved Gene Symbol: PFKP
Cytogenetic location: 10p15.2 Genomic coordinates (GRCh38): 10:3,067,548-3,136,805 (from NCBI)
The PFKP gene encodes the platelet 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. The PFKP gene, which maps to chromosome 10p, is also expressed in fibroblasts. See also the muscle (PFKM; 610681) and liver (PFKL; 171860) isoforms of phosphofructokinase, which map to chromosomes 12q13 and 21q22, respectively.
Vora (1981) determined that full tetrameric phosphofructokinase enzyme expressed in platelets can be composed of subunits P4, P3L, and P2L2.
Simpson and Fothergill-Gilmore (1991) isolated a cDNA corresponding to the PFKP gene from a human lymphocyte Raji cell line cDNA library using a cDNA for human muscle PFK as a probe. The deduced amino acid sequence showed 71% identity to the amino acid sequence for the human muscle isoenzyme and 63% identity to the human liver isoenzyme.
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.
Park et al. (2020) reported that the transfer of human bronchial epithelial cells from stiff to soft substrates caused a downregulation of glycolysis via proteasomal degradation of the rate-limiting metabolic enzyme PFK. PFK degradation was triggered by the disassembly of stress fibers, which released the PFK-targeting E3 ubiquitin ligase TRIM21 (109092). Transformed non-small-cell lung cancer cells, which maintain high glycolytic rates regardless of changing environmental mechanics, retained PFK expression by downregulating TRIM21, and by sequestering residual TRIM21 on a stress fiber subset that is insensitive to substrate stiffness. Park et al. (2020) concluded that their data revealed a mechanism by which glycolysis responds to architectural features of the actomyosin cytoskeleton, thus coupling cell metabolism to the mechanical properties of the surrounding tissue. These processes enable normal cells to tune energy production in variable microenvironments, whereas the resistance of the cytoskeleton in response to mechanical cues enables the persistence of high glycolytic rates in cancer cells despite constant alterations of the tumor tissue.
Weil et al. (1980) developed a method of specific immunoprecipitation of human PFK and used it to locate the structural gene for fibroblast PFK (PFKF) to chromosome 10 in somatic cell hybrids. Vora et al. (1983) assigned the PFKP gene to 10p by use of a mouse antihuman P-subunit-specific antiserum in the study of human/rodent somatic cell hybrids. A single discordant hybrid cell containing only 10q did not express PFKP, and fibroblasts from a patient with duplication of 10p exhibited PFK activity values 180% of normal.
Schwartz et al. (1984) confirmed the assignment of PFKP and hexokinase-1 (HK1; 142600) to 10p by dosage effects in a case of 10p partial trisomy. The synteny of PFKP and HK1 may have functional significance because the enzymes which they encode are the primary and secondary control points of the glycolytic pathway.
By use of the cDNA clone as a biotinylated probe for in situ hybridization to human chromosome spreads, Morrison et al. (1992) assigned the PFKP gene to chromosome 10p15.3-p15.2.
Francke (1983) suggested that this form of PFK is best called the 'platelet' type and symbolized PFKP because it is the only form made by platelets, whereas fibroblasts have more than one form of PFK.
Francke, U. Personal Communication. New Haven, Conn. 8/1983.
Gonzalez, G. H., Billerbeck, A. E. C., Takayama, L. C., Wajntal, A. Duplication 10p in a girl due to a maternal translocation t(10;14)(p11;q12). Am. J. Med. Genet. 14: 159-167, 1983. [PubMed: 6829605] [Full Text: https://doi.org/10.1002/ajmg.1320140122]
Morrison, N., Simpson, C., Fothergill-Gilmore, L., Boyd, E., Connor, J. M. Regional chromosomal assignment of the human platelet phosphofructokinase gene to 10p15. Hum. Genet. 89: 105-106, 1992. [PubMed: 1533608] [Full Text: https://doi.org/10.1007/BF00207053]
Park, J. S., Burckhardt, C. J., Lazcano, R., Solis, L. M., Isogai, T., Li, L., Chen, C. S., Gao, B., Minna, J. D., Bachoo, R., DeBerardinis, R. J., Danuser, G. Mechanical regulation of glycolysis via cytoskeleton architecture. Nature 578: 621-626, 2020. [PubMed: 32051585] [Full Text: https://doi.org/10.1038/s41586-020-1998-1]
Schwartz, S., Cohen, M. M., Panny, S. R., Beisel, J. H., Vora, S. Duplication of chromosome 10p: confirmation of regional assignments of platelet-type phosphofructokinase. Am. J. Hum. Genet. 36: 750-759, 1984. [PubMed: 6236690]
Simpson, C. J., Fothergill-Gilmore, L. A. Isolation and sequence of a cDNA encoding human platelet phosphofructokinase. Biochem. Biophys. Res. Commun. 180: 197-203, 1991. [PubMed: 1834056] [Full Text: https://doi.org/10.1016/s0006-291x(05)81276-8]
Vora, S., Miranda, A. F., Hernandez, E., Francke, U. Regional assignment of the human gene for platelet-type phosphofructokinase (PFKP) to chromosome 10p: novel use of polyspecific rodent antisera to localize human enzyme genes. Hum. Genet. 63: 374-379, 1983. [PubMed: 6222962] [Full Text: https://doi.org/10.1007/BF00274765]
Vora, S., Seaman, C., Durham, S., Piomelli, S. Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system. Proc. Nat. Acad. Sci. 77: 62-66, 1980. [PubMed: 6444721] [Full Text: https://doi.org/10.1073/pnas.77.1.62]
Vora, S. Isozymes of human phosphofructokinase in blood cells and cultured cell lines: molecular and genetic evidence for a trigenic system. Blood 57: 724-732, 1981. [PubMed: 6451249]
Weil, D., Cottreau, D., Cong, N. V., Rebourcet, R., Foubert, C., Gross, M.-S., Dreyfus, J.-C., Kahn, A. Assignment of the gene for F-type phosphofructokinase to human chromosome 10 by somatic cell hybridization and specific immunoprecipitation. Ann. Hum. Genet. 44: 11-16, 1980. [PubMed: 6459753] [Full Text: https://doi.org/10.1111/j.1469-1809.1980.tb00941.x]
Yi, W., Clark, P. M., Mason, D. E., Keenan, M. C., Hill, C., Goddard, W. A., III, Peters, E. C., Driggers, E. M., Hsieh-Wilson, L. C. Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337: 975-980, 2012. [PubMed: 22923583] [Full Text: https://doi.org/10.1126/science.1222278]