PFKFB4

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4
PDB rendering based on 3bif.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3bif​, 1bif​, 2bif​
Identifiers
Symbol	PFKFB4
External IDs	OMIM: 605320 MGI: 2687284 HomoloGene: 48288 GeneCards: PFKFB4 Gene
EC number	2.7.1.105, 3.1.3.46
Gene ontology Molecular function • 6-phosphofructo-2-kinase activity • fructose-2,6-bisphosphate 2-phosphatase activity • ATP binding Cellular component • cytosol Biological process • carbohydrate metabolic process • fructose metabolic process • fructose 2,6-bisphosphate metabolic process • glucose metabolic process • protein dephosphorylation • small molecule metabolic process • carbohydrate phosphorylation • canonical glycolysis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5210	270198
Ensembl	ENSG00000114268	ENSMUSG00000025648
UniProt	Q16877	Q6DTY7
RefSeq (mRNA)	NM_004567	NM_001039215
RefSeq (protein)	NP_004558	NP_766607
Location (UCSC)	Chr 3: 48.52 – 48.56 Mb	Chr 9: 108.99 – 109.03 Mb
PubMed search

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 also known as PFKFB4 is an enzyme which in humans is encoded by the PFKFB4 gene.^[1][2]

Function

The bifunctional 6-phosphofructo-2-kinase (EC 2.7.1.105)/fructose-2,6-bisphosphatase (EC 3.1.3.46) (PFKFB) regulates the steady-state concentration of fructose 2,6-bisphosphate, an activator of a key regulatory enzyme of glycolysis, phosphofructokinase.
Latest research made by scientists at Cancer Research UK’s London Research Institute show that an enzyme called PFKFB4 is essential for balancing these two processes – making sure the cell’s energy needs are met without allowing free radicals to build up and trigger cell death. Study leader Dr. Almut Schulze, said: “Our study suggests that PFKFB4 acts to fine-tune the process by which cells convert glucose into energy. Blocking this enzyme in prostate cancer cells grown in the lab stalled growth and triggered a catastrophic build-up of free-radicals, suggesting that it could be a suitable drug target. Importantly, this route to energy production is common to many different types of cancer, suggesting that drugs to target it could potentially be used to treat a variety of cancers.”^[3]

References

1. Sakai A, Kato M, Fukasawa M, Ishiguro M, Furuya E, Sakakibara R (March 1996). "Cloning of cDNA encoding for a novel isozyme of fructose 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase from human placenta". J. Biochem. 119 (3): 506–11. doi:10.1093/oxfordjournals.jbchem.a021270. PMID 8830046.
2. Manzano A, Pérez JX, Nadal M, Estivill X, Lange A, Bartrons R (March 1999). "Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene". Gene 229 (1-2): 83–9. doi:10.1016/S0378-1119(99)00037-2. PMID 10095107.
3. Ros, Susana; Claudio R. Santos; Sofia Moco; Franziska Baenke; Gavin Kelly; Michael Howell; Nicola Zamboni; Almut Schulze (2012-03-20). "Functional Metabolic Screen Identifies 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 as an Important Regulator of Prostate Cancer Cell Survival". Cancer Discovery 2 (4): 328–343. doi:10.1158/2159-8290.CD-11-0234.

Further reading

• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Pilkis SJ, Claus TH, Kurland IJ, Lange AJ (1995). "6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme.". Annu. Rev. Biochem. 64 (1): 799–835. doi:10.1146/annurev.bi.64.070195.004055. PMID 7574501.
• Gómez M, Manzano A, Navarro-Sabaté A; et al. (2005). "Specific expression of pfkfb4 gene in spermatogonia germ cells and analysis of its 5'-flanking region.". FEBS Lett. 579 (2): 357–62. doi:10.1016/j.febslet.2004.11.096. PMID 15642344.
• Minchenko OH, Ochiai A, Opentanova IL, et al. (2005). "Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors.". Biochimie 87 (11): 1005–10. doi:10.1016/j.biochi.2005.04.007. PMID 15925437.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Minchenko O, Opentanova I, Minchenko D, et al. (2004). "Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation.". FEBS Lett. 576 (1-2): 14–20. doi:10.1016/j.febslet.2004.08.053. PMID 15474002.
• Bobarykina AY, Minchenko DO, Opentanova IL, et al. (2006). "Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers.". Acta Biochim. Pol. 53 (4): 789–99. PMID 17143338.
• Susana Ros, Claudio R. Santos, Sofia Moco, Franziska Baenke, Gavin Kelly, Michael Howell, Nicola Zamboni, Almut Schulze; et al. "Functional Metabolic Screen Identifies 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 as an Important Regulator of Prostate Cancer Cell Survival.". Cancer Discovery.