Property Summary

NCBI Gene PubMed Count 66
PubMed Score 184.98
PubTator Score 126.71

Knowledge Summary

Patent (10,885)


  Differential Expression (26)

Disease log2 FC p
Rheumatoid Arthritis 1.300 3.2e-02
psoriasis -1.600 1.1e-04
osteosarcoma -2.208 1.4e-03
group 3 medulloblastoma -1.600 3.4e-03
astrocytoma 2.400 5.6e-03
glioblastoma 1.200 2.6e-02
atypical teratoid/rhabdoid tumor -1.300 3.2e-04
medulloblastoma, large-cell -2.100 7.3e-05
acute quadriplegic myopathy 1.440 1.3e-02
type 2 diabetes -1.208 4.3e-02
tuberculosis and treatment for 3 months -2.000 4.6e-04
primary pancreatic ductal adenocarcinoma 1.713 1.1e-02
ulcerative colitis 3.400 2.9e-10
breast carcinoma -1.500 1.6e-03
fibroadenoma -1.800 2.8e-02
diabetes mellitus -1.800 3.3e-02
lung carcinoma -2.400 9.0e-30
gastric carcinoma 1.600 9.8e-03
Bipolar Disorder 1.122 3.9e-02
mucosa-associated lymphoid tissue lympho... 1.624 3.5e-02
ductal carcinoma in situ -2.800 5.5e-05
invasive ductal carcinoma -2.300 2.6e-03
ovarian cancer 1.500 3.3e-03
pituitary cancer -1.200 3.8e-04
pancreatic cancer 1.800 2.8e-03
dermatomyositis 2.200 2.6e-03

 MGI Phenotype (1)

Protein-protein Interaction (8)

Gene RIF (42)

27491149 The expression of PFKFB3, PFKFB4, NAMPT, and TSPAN13 is strongly up-regulated in pediatric glioma.
26827442 Insulin resistance in obese boys leads to up-regulation of INSIG2 gene expression as well as to down-regulation of PFKFB1, PFKFB3, and HK2 genes in the blood cells as compared to obese patients with normal insulin sensitivity.
26718307 a novel role of PFKFB3 in glycolytic metabolism and ER stress of OA cartilage explants and chondrocytes
26681033 MicroRNA-26b inhibits osteosarcoma cell migration and invasion by down-regulating PFKFB3 expression
26530697 Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of colorectal cancer (CRC).
26337471 Data indicate that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) and phosphofructokinase (PFK1) expression allows discrimination between induced pluripotent stem cells (iPS) and cancer stem cells (CSCs).
26322680 Data show that inhibition of AMP-Activated kinase (AMPK) or 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) results in enhanced cell death in mitosis.
26171876 Shh regulates PFKFB3 activation in breast cancer cells.
26093295 study demonstrated that miR-206 regulated PFKFB3 expression in breast cancer cells, thereby stunting glycolysis, cell proliferation and migration
25672572 A binding site for miR-26b was predicted in the 3'UTR of PFKFB3. miR-26b overexpression repressed PFKFB3 mRNA and protein levels.
25359860 Shear stress-mediated repression of endothelial cell metabolism via KLF2 and PFKFB3 controls endothelial cell phenotype.
25032860 PFKFB3 promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27.
24700124 PFKFB3 is a promising target for the reduction of endothelial glycolysis and its related pathological angiogenesis
24633012 Reduced methylation of PFKFB3 shifted glucose utilization from glycolysis toward the pentose phosphate pathway.
24515104 estrogen receptor directly promotes PFKFB3 mRNA transcription
24332967 blockade of PFKFB3 by the small molecule 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) reduced vessel sprouting.
24295899 PFKFB3 regulates oxidative stress homeostasis via its S-glutathionylation in cancer.
24204309 Because deregulation of endometrial SRC-2 expression has been associated with common gynecological disorders of reproductive-age women, this signaling pathway, involving SRC-2 and PFKFB3
24043759 Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells.
23911327 Study showed that endothelial cells (ECs)relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation.
23548149 Stress stimuli affect PFKFB3 transcriptional regulation and kinase activation by protein phosphorylation and glycolysis in cancer cells.
22275052 Low bisphosphatase activity of PFKFB3 is solely due to the presence of a serine at residue 302.
22106309 The breakdown of PFKFB3 during S phase occurs specifically via a distinct residue (S(273)) within the conserved recognition site for SCF-beta-TrCP.
21987444 The allelic deletion of PFKFB3 resulted in a decrease of PFKFB3 mRNA level accompanied by a lower PFKFB3 protein level.
21860432 inducible PFKFB3 is required for increased growth, metabolic activity and is regulated through active JAK2 and STAT5.
21402913 Data demonstrate that PFKFB3 is essential for cell division and that it is regulated by APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP.
20453422 Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3.
20080744 Glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is degraded by the E3 ubiquitin ligase APC/C-Cdh1.
19490427 Our results demonstrate that the splice variant UBI2K4 impedes the tumour cell growth and might serve as a tumour suppressor in astrocytic tumours.
19473963 ectopic expression of PFKFB3 increased the expression of several key cell cycle proteins, including cyclin-dependent kinase (Cdk)-1, Cdc25C, and cyclin D3 and decreased the expression of the cell cycle inhibitor p27
18039179 PFK-2/FBPase-2 protein rather than its product fructose 2,6-P(2) is the over-riding determinant of glucose-induced insulin secretion through regulation of glucokinase activity or subcellular targeting.
17499765 Results show a direct substrate-substrate interaction in the kinase domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3).
17143338 PFKFB-4 and PFKFB-3 genes are expressed in gastric and pancreatic cancer cells, they strongly respond to hypoxia via a HIF-1alpha dependent mechanism and possibly have a significant role in the Warburg effect which is found in malignant cells
16698023 The results obtained highlight the importance of uPFK-2 on the regulation of glycolysis, on cell viability and proliferation and also on anchorage-independent growth.
16385451 Observational study of gene-disease association. (HuGE Navigator)
16311927 Our results clearly demonstrated the existence of splice isoform of PFKFB-4 mRNA in the DB-1 melanoma cells and its overexpression under hypoxic conditions.
16306349 Insulin induces the phosphorylation of PFKFB3 protein, expanding the role of these structurally unique iPFK-2/PFKFB3 isoforms in the metabolic regulation of adipocytes.
16115917 Findings support a potential role for the phosphorylation of PFKFB3 protein in the progression of cancer and angiogenesis.
15896703 kinase activity of human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is regulated via inhibition by phosphoenolpyruvate
15466858 pfkfb3 is a hypoxia-inducible gene that is stimulated through HIF interaction with the consensus HRE site in its promoter region
12963966 PFKFB3 cloning and characterization
12935880 The results show the expression of the pfkfb3 gene in and its downregulation during myogenic cell differentiation, the decrease of uPFK-2 isozyme levels, product of pfkfb3 gene, is due to its degradation through the ubiquitin-proteasome pathway

AA Sequence

PSCLPPEVPTQLPGQNMKGSRSSADSSRKH                                            491 - 520

Text Mined References (73)

PMID Year Title
26718307 2016 PFKFB3 modulates glycolytic metabolism and alleviates endoplasmic reticulum stress in human osteoarthritis cartilage.
26681033 2015 MicroRNA-26b inhibits osteosarcoma cell migration and invasion by down-regulating PFKFB3 expression.
26530697 2016 Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer.
26337471 2015 The expression pattern of PFKFB3 enzyme distinguishes between induced-pluripotent stem cells and cancer stem cells.
26322680 2015 AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest.
26171876 2015 Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation.
26093295 2015 Overexpression of miR-206 suppresses glycolysis, proliferation and migration in breast cancer cells via PFKFB3 targeting.
25849762 2015 Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3.
25672572 2015 miR-26b inhibits proliferation, migration, invasion and apoptosis induction via the downregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 driven glycolysis in osteosarcoma cells.
25359860 2015 Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3.
25117820 2014 Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100.
25032860 2014 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27.
24999842 2014 Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.
24700124 2014 Endothelial PFKFB3 plays a critical role in angiogenesis.
24633012 2014 Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway.
24515104 2014 Estradiol stimulates glucose metabolism via 6-phosphofructo-2-kinase (PFKFB3).
24332967 2014 Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis.
24295899 2014 PFKFB3 regulates oxidative stress homeostasis via its S-glutathionylation in cancer.
24204309 2013 Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization.
24043759 2013 Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells.
23911327 2013 Role of PFKFB3-driven glycolysis in vessel sprouting.
23548149 2013 PFKFB3 activation in cancer cells by the p38/MK2 pathway in response to stress stimuli.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22275052 2012 Molecular basis of the fructose-2,6-bisphosphatase reaction of PFKFB3: transition state and the C-terminal function.
22106309 2011 Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells.
21987444 2011 LOH on 10p14-p15 targets the PFKFB3 gene locus in human glioblastomas.
21860432 2012 The JAK2V617F oncogene requires expression of inducible phosphofructokinase/fructose-bisphosphatase 3 for cell growth and increased metabolic activity.
21402913 2011 Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle.
20453422 2010 Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3.
20080744 2010 E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19490427 2009 The PFKFB3 splice variant UBI2K4 is downregulated in high-grade astrocytomas and impedes the growth of U87 glioblastoma cells.
19473963 2009 Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18039179 2008 A role for PFK-2/FBPase-2, as distinct from fructose 2,6-bisphosphate, in regulation of insulin secretion in pancreatic beta-cells.
17499765 2007 A direct substrate-substrate interaction found in the kinase domain of the bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17143338 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.
16698023 2006 PFKFB3 gene silencing decreases glycolysis, induces cell-cycle delay and inhibits anchorage-independent growth in HeLa cells.
16385451 2006 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16316985 2006 Crystal structure of the hypoxia-inducible form of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3): a possible new target for cancer therapy.
16311927 2005 Splice isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4: expression and hypoxic regulation.
16306349 2005 Expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase/PFKFB3 isoforms in adipocytes and their potential role in glycolytic regulation.
16115917 2005 Phosphorylation of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase/PFKFB3 family of glycolytic regulators in human cancer.
15896703 2005 The kinase activity of human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is regulated via inhibition by phosphoenolpyruvate.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15466858 2004 6-Phosphofructo-2-kinase (pfkfb3) gene promoter contains hypoxia-inducible factor-1 binding sites necessary for transactivation in response to hypoxia.
15164054 2004 The DNA sequence and comparative analysis of human chromosome 10.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12963966 2003 Cloning and chromosomal characterization of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 gene (PFKFB3, iPFK2).
12935880 2003 Regulation of ubiquitous 6-phosphofructo-2-kinase by the ubiquitin-proteasome proteolytic pathway during myogenic C2C12 cell differentiation.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12384552 2002 High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers.
12065600 2002 The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase.
11245987 2001 The human ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene (PFKFB3): promoter characterization and genomic structure.
11245921 2001 Splice isoforms of ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in human brain.
10673355 2000 Identification of the promoter region of human placental 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.
10508479 1999 Antigens recognized by autologous antibody in patients with renal-cell carcinoma.
10095107 1999 Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.
10077634 1999 An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect.
10072580 1998 Molecular cloning, expression, and chromosomal localization of a ubiquitously expressed human 6-phosphofructo-2-kinase/ fructose-2, 6-bisphosphatase gene (PFKFB3).
9828130 1998 Cloning of ARE-containing genes by AU-motif-directed display.
9464277 1998 Expression of human placental-type 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase in various cells and cell lines.
9276680 1997 Characterization of a human placental fructose-6-phosphate, 2-kinase/fructose-2,6-bisphosphatase.
9146922 1997 The third human isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) map position 10p14-p15.
9092801 1997 Identification of PRG1, a novel progestin-responsive gene with sequence homology to 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.
8830046 1996 Cloning of cDNA encoding for a novel isozyme of fructose 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase from human placenta.
7574501 1995 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme.
2837207 1988 Molecular cloning, sequence analysis, and expression of a human liver cDNA coding for fructose-6-P,2-kinase:fructose-2,6-bisphosphatase.