PFKFB4

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.[5][6]

PFKFB4
Identifiers
Aliases	PFKFB4, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4
External IDs	OMIM: 605320 MGI: 2687284 HomoloGene: 48288 GeneCards: PFKFB4
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.31 Start 48,517,684 bp[1] End 48,562,015 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 F2 Start 108,991,778 bp[2] End 109,032,228 bp[2]
Gene ontology Molecular function • transferase activity • nucleotide binding • fructose-2,6-bisphosphate 2-phosphatase activity • catalytic activity • hydrolase activity • ATP binding • kinase activity • 6-phosphofructo-2-kinase activity Cellular component • cytosol Biological process • fructose metabolic process • metabolism • fructose 2,6-bisphosphate metabolic process • phosphorylation • dephosphorylation • carbohydrate phosphorylation • positive regulation of glycolytic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5210	270198
Ensembl	ENSG00000114268	ENSMUSG00000025648
UniProt	Q16877	Q6DTY7
RefSeq (mRNA)	NM_004567 NM_001317134 NM_001317135 NM_001317136 NM_001317137 NM_001317138	NM_001039215 NM_001039216 NM_001039217 NM_173019
RefSeq (protein)	NP_001304063 NP_001304064 NP_001304065 NP_001304066 NP_001304067 NP_004558	NP_766607
Location (UCSC)	Chr 3: 48.52 – 48.56 Mb	Chr 9: 108.99 – 109.03 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.

In 2012 research 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.”[7]

References

1. GRCh38: Ensembl release 89: ENSG00000114268 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025648 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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". Journal of Biochemistry. 119 (3): 506–11. doi:10.1093/oxfordjournals.jbchem.a021270. PMID 8830046.
6. 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.
7. Ros S, Santos CR, Moco S, Baenke F, Kelly G, Howell M, Zamboni N, Schulze A (April 2012). "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): 328–43. doi:10.1158/2159-8290.CD-11-0234. PMID 22576210.

Further reading

• Pilkis SJ, Claus TH, Kurland IJ, Lange AJ (1995). "6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme". Annual Review of Biochemistry. 64 (1): 799–835. doi:10.1146/annurev.bi.64.070195.004055. PMID 7574501.
• Gómez M, Manzano A, Navarro-Sabaté A, Duran J, Obach M, Perales JC, Bartrons R (January 2005). "Specific expression of pfkfb4 gene in spermatogonia germ cells and analysis of its 5'-flanking region". FEBS Letters. 579 (2): 357–62. doi:10.1016/j.febslet.2004.11.096. PMID 15642344.
• Minchenko OH, Ochiai A, Opentanova IL, Ogura T, Minchenko DO, Caro J, Komisarenko SV, Esumi H (November 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.
• Minchenko O, Opentanova I, Minchenko D, Ogura T, Esumi H (October 2004). "Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation". FEBS Letters. 576 (1–2): 14–20. doi:10.1016/j.febslet.2004.08.053. PMID 15474002.
• Bobarykina AY, Minchenko DO, Opentanova IL, Moenner M, Caro J, Esumi H, Minchenko OH (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 Biochimica Polonica. 53 (4): 789–99. PMID 17143338.
• Ros S, Santos CR, Moco S, Baenke F, Kelly G, Howell M, Zamboni N, Schulze A (2012). "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): 328–43. doi:10.1158/2159-8290.CD-11-0234. PMID 22576210.