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Information on EC 2.7.1.105 - 6-phosphofructo-2-kinase and Organism(s) Homo sapiens
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EC Tree
2.7.1.105 6-phosphofructo-2-kinaseIUBMB Comments
Not identical with EC 2.7.1.11 6-phosphofructokinase. The enzyme co-purifies with EC 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase.
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Word Map
- 2.7.1.105
- 2,6-bisphosphate
- fructose-2,6-bisphosphate
- pfkfb3
- 6-phosphofructo-1-kinase
-
camp-dependent
- phosphofructokinase-1
- mgatp
- phosphoenzyme
- medicine
- sn-glycerol
-
cyclic-amp-dependent
-
fru-6-p
-
3-3hglucose
- fbpase-2
- pharmacology
- diagnostics
- drug development
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria
Synonyms
6-phosphofructo-2-kinase, phosphofructokinase 2, phosphofructokinase-2, upfk-2, inducible 6-phosphofructo-2-kinase, fructose 6-phosphate 2-kinase, ipfk2, tpfk-2, phosphofructokinase-2/fructose bisphosphatase-2, 6-phosphofructose 2-kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
6-phosphofructo-2-kinase
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase
6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase
-
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
6-phosphofructose 2-kinase
-
-
-
-
ATP:D-fructose-6-phosphate 2-phosphotransferase
-
-
-
-
fructose 6-phosphate 2-kinase
-
-
-
-
kinase, 6-phosphofructo-2-(phosphorylating)
-
-
-
-
Pfk-2
PFK-2/FBPase-2
the bifunctional enzyme has 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities
PFKFB1
PFKFB2
PFKFB3
PFKFB4
phosphofructokinase 2
-
-
-
-
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase
-
-
-
-
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase
-
PFKFB2
the bifunctional enzyme has 6-phosphofructo-2-kinase and fructose-2,6-biphosphatase activities
PFKFB3
-
PFKFB3
bifunctional enzyme with 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities
PFKFB3
the bifunctional enzyme has 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities
PFKFB4
bifunctional enzyme with 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate
random mechanism
ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate
bifunctional protein: 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, reverse reaction catalysed by fructose 2,6-bisphosphatase: 3.1.3.46
-
ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate
bifunctional protein: 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, reverse reaction catalysed by fructose 2,6-bisphosphatase: 3.1.3.46
ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate
high 6-phosphofructo-2-kinase activity compared to the fructose 2,6-bisphosphatase
-
ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate
HBP1 and HBP2 both show a random order equilibrium bi bi mechanism, bifunctional enzyme comprises both 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase, EC 3.1.3.46, activities
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:beta-D-fructose-6-phosphate 2-phosphotransferase
Not identical with EC 2.7.1.11 6-phosphofructokinase. The enzyme co-purifies with EC 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase.
CAS REGISTRY NUMBER
COMMENTARY
78689-77-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
r
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
regulation of glycolysis
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
the inducible enzyme is an important regulator of glycolysis that may be responsible for sustaining the high glycolytic flux of rapidly proliferating leukemia cells
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
bifunctional enzyme catalyzes the forward and reverse reaction using different catalytic sites
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
PFKFB3 plays a crucial role in the progression of cancerous cells by enabling their glycolytic pathways even under severe hypoxic conditions
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
PFKFB3 is a potent stimulator of glycolysis, up-regulated by inflammatory and hypoxic stimuli
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
PFKFB3 is a potent stimulator of glycolysis, up-regulated by inflammatory and hypoxic stimuli, role in the progression of cancerous cells, antiproliferative effects during inhibitor incubation determined
-
-
?
additional information
?
-
-
also catalyses the degradation of fructose 2,6-bisphosphate (EC 3.1.3.46)
-
-
?
additional information
?
-
-
also catalyses the degradation of fructose 2,6-bisphosphate (EC 3.1.3.46)
-
-
?
additional information
?
-
-
also catalyses the degradation of fructose 2,6-bisphosphate (EC 3.1.3.46)
-
-
?
additional information
?
-
-
also catalyses the degradation of fructose 2,6-bisphosphate (EC 3.1.3.46)
-
-
?
additional information
?
-
also catalyses the degradation of fructose 2,6-bisphosphate (EC 3.1.3.46)
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the synthesis, 6-phosphofructo-2-kinase, and hydrolysis, fructose-2,6-bisphosphatase, of beta-D-fructose 2,6-bisphosphate, an activator of glycolysis and an inhibitor of gluconeogenesis
-
-
?
additional information
?
-
-
it is unlikely that protein kinase Czeta is required for activation of 6-phosphofructo-2-kinase by insulin in heart
-
-
?
additional information
?
-
-
PFKFB3 is activated by mitogenic inflammatory and hypoxic stimuli. PFKFB4 controls glycolytic flux to lactate and the nonoxidatibe pentose shunt, and is selectively required for the tumorigenic growth of ras-transformed cells
-
-
?
additional information
?
-
-
the expression of the inducible PFK2/FBPase is selectively necessary for the control of glycolytic flux in cells transformed with ras
-
-
?
additional information
?
-
expression analysis in different tumor specimens with high and low malignity grades, high expression of the PFKFB3 protein as an explanation for high glycolytic flux and lactate production in these tumors
-
-
?
additional information
?
-
expression analysis in different tumor specimens with high and low malignity grades, high expression of the PFKFB3 protein as an explanation for high glycolytic flux and lactate production in these tumors
-
-
?
additional information
?
-
expression analysis in different tumor specimens with high and low malignity grades, high expression of the PFKFB3 protein as an explanation for high glycolytic flux and lactate production in these tumors
-
-
?
additional information
?
-
expression analysis in different tumor specimens with high and low malignity grades, high expression of the PFKFB3 protein as an explanation for high glycolytic flux and lactate production in these tumors
-
-
?
additional information
?
-
recombinant human PFKFB4 kinase activity is 4.3-fold greater than its phosphatase activity
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
-
r
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
-
regulation of glycolysis
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
the inducible enzyme is an important regulator of glycolysis that may be responsible for sustaining the high glycolytic flux of rapidly proliferating leukemia cells
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
PFKFB3 plays a crucial role in the progression of cancerous cells by enabling their glycolytic pathways even under severe hypoxic conditions
-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
PFKFB3 is a potent stimulator of glycolysis, up-regulated by inflammatory and hypoxic stimuli
-
-
?
additional information
?
-
the bifunctional enzyme catalyzes the synthesis, 6-phosphofructo-2-kinase, and hydrolysis, fructose-2,6-bisphosphatase, of beta-D-fructose 2,6-bisphosphate, an activator of glycolysis and an inhibitor of gluconeogenesis
-
-
?
additional information
?
-
-
it is unlikely that protein kinase Czeta is required for activation of 6-phosphofructo-2-kinase by insulin in heart
-
-
?
additional information
?
-
-
PFKFB3 is activated by mitogenic inflammatory and hypoxic stimuli. PFKFB4 controls glycolytic flux to lactate and the nonoxidatibe pentose shunt, and is selectively required for the tumorigenic growth of ras-transformed cells
-
-
?
additional information
?
-
-
the expression of the inducible PFK2/FBPase is selectively necessary for the control of glycolytic flux in cells transformed with ras
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(2-bromoacetamido)ethyl phosphate
an irreversible inhibitor of PFK-2 in several cancer cell lines
2-(5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline-5-carbonitrile
-
4-(4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-5-bromo-6-oxopyridazin-1(6H)-yl)benzonitrile
-
4-bromo-2-phenyl-5-(((tetrahydrofuran-2-yl)methyl)amino)pyridazin-3(2H)-one
-
4-bromo-2-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzyl-4-bromopyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(3-phenylpropyl)pyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-((2-(dimethylamino)ethyl)-amino)benzyl)pyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-(trifluoromethoxy)phenyl)-pyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-chlorophenyl)pyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-iodobenzyl)pyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(pyrimidin-5-yl)pyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenethylpyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenylpyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-chloro-2-phenylpyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-ethoxy-2-phenylpyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-iodo-2-phenylpyridazin-3(2H)-one
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-isopropyl-2-phenylpyridazin-3(2H)-one
-
beta-D-fructose 6-phosphate
modeling of beta-D-fructose 6-phosphate as inhibitor
ethyl 1-(6-oxo-1-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1,6-dihydropyridazin-4-yl)-1H-1,2,3-triazole-4-carboxylate
-
phosphoenolpyruvate
HBP1 and HBP2, the bifunctional enzyme is regulated via inhibition by phosphoenolpyruvate, uncompetitive against ATP, noncompetitive against beta-D-fructose 6-phosphate
1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one
the inhibitor causes a rapid induction of apoptosis in transformed cells, has adequate pharmacokinetic properties, suppresses the glucose uptake and growth of Lewis lung carcinomas in syngeneic mice and yields anti-tumor effects in three human xenograft models of cancer in athymic mice that are comparable to FDA-approved chemotherapeutic agents
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
(3PO), small-molecule inhibitor, mixed inhibition mechanism, both competitive and uncompetitive inhibition, suppresses glycolytic flux and is cytostatic to neoplastic cells, inhibits activity of recombinantly expressed PFKFB3
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
the PFKFB3 inhibitor, 3PO, increases p27 protein in Lewis lung carcinoma cells in vitro and in vivo
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
3PO, a weak competitive inhibitor of PFKFB3, reduces the glucose metabolism and proliferation of cancer cells
additional information
enzyme structure-activity relationships, screening of a small-molecule library, and design and synthesis of 5-triazolo-2-arylpyridazinone analogus inhibitors, molecular docking using the X-ray structure for human PFKFB3, PDB ID 2AXN, overview
-
additional information
synthesis and screening of 3PO inhibitor derivatives for inhibitory potency against isozyme PFKFB3, overview. 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one displays improved pharmacokinetic properties relative to 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
-
additional information
-
synthesis and screening of 3PO inhibitor derivatives for inhibitory potency against isozyme PFKFB3, overview. 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one displays improved pharmacokinetic properties relative to 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
-
additional information
not inhibited by up to 0.75 mM 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Insulin
stimulates glycolysis in the heart by increasing glucose transport and activating H-PFK2 by phosphorylating Ser466 and Ser483 through protein kinase B within the C-terminal regulatory domain. Phosphorylation of Ser466 or Thr475 by protein kinase C does not change the enzyme activity. Phosphorylation at Ser84 possibly counteracts the effects of phosphorylation at the activating C-terminal sites
-
additional information
amino acids increase beta-D-fructose 2,6-bisphosphate concentration in HeLa and in MCF-7 human cells, molecular mechanisms involved differ from those observed with insulin. Only essential amino acids without glutamine are required to activate the PI3K/mTORC2 and p38/MAPKAPK-2 pathways and to increase the beta-D-fructose 2,6-bisphosphate concentration. The observed effects in signaling and metabolism are produced by a mixture of essential amino acids
-
additional information
-
amino acids increase beta-D-fructose 2,6-bisphosphate concentration in HeLa and in MCF-7 human cells, molecular mechanisms involved differ from those observed with insulin. Only essential amino acids without glutamine are required to activate the PI3K/mTORC2 and p38/MAPKAPK-2 pathways and to increase the beta-D-fructose 2,6-bisphosphate concentration. The observed effects in signaling and metabolism are produced by a mixture of essential amino acids
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
recombinant wild-type and mutant enzymes, Km for phosphorylated wild-type enzyme and mutants with beta-D-fructose 6-phosphate and beta-D-fructose 2,6-bisphosphate, kinetics, modeling
-
0.0064
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, HBP1 mutant S477D
0.0066
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, HBP1 mutants T470D and S460D/T470D
0.0067
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, HBP1 mutant S460D
0.0071
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, HBP1 mutant H253A/S460D
0.0071
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, wild-type HBP1
0.0073
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, HBP1 mutant H253A
0.0074
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, His-tagged wild-type HBP2
0.008
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, His-tagged wild-type HBP1
0.0092
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant Hnon-phosphorylated, is-tagged HBP1 deletion mutant
0.0095
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, His-tagged HBP1 mutant S302R
0.013
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged chimeric mutant enzyme, phosphorylated or nonphosphorylated
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
kcat of wild-type and mutant HBP1 and of HBP2 with beta-D-fructose 2,6-bisphosphate, kcat for phosphorylated wild-type enzyme and mutants with beta-D-fructose 6-phosphate and beta-D-fructose 2,6-bisphosphate
-
0.391
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant H253A
0.394
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant S460D
0.394
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant S460D/T470D
0.399
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged HBP1 mutant S302R
0.401
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant H253A/S460D
0.405
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant S477D
0.407
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant wild-type HBP1
0.43
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged wild-type HBP1
0.435
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant T470
0.447
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged wild-type HBP2
0.654
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, His-tagged chimeric mutant enzyme
0.678
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant phosphorylated, His-tagged chimeric mutant enzyme
0.696
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged HBP1 deletion mutant
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.025
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
inhibition of recombinant PFKFB3 protein, no inhibition of purified PFK-1 activity
additional information
additional information
modeling of inhibition of HBP1 and HBP2 by phosphoenolpyruvate and beta-D-fructose 6-phosphate, Km for phosphorylated wild-type enzyme and mutants with beta-D-fructose 6-phosphate and beta-D-fructose 2,6-bisphosphate
-
8.5
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant S460D/T470D
9.2
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant S460D
9.5
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant H253A/S460D
9.6
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged HBP1 deletion mutant
9.7
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant S477D
10.9
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged HBP1 mutant S302R
11.1
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant H253A
11.8
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged wild-type HBP2
12.2
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant His-tagged wild-type HBP1
12.7
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant non-phosphorylated, His-tagged chimeric mutant enzyme
13
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant HBP1 mutant T470
13.4
beta-D-fructose 6-phosphate
pH 7.5, 30°C, recombinant phosphorylated, His-tagged chimeric mutant enzyme
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.026
(2E)-3-(pyridin-3-yl)-1-(pyridin-4-yl)prop-2-en-1-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
1
2-((5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)amino)acetamide
Homo sapiens
above, pH 7.5, 30°C, recombinant GST-tagged enzyme
0.5
2-(5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline-5-carbonitrile
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.027
2-hydroxy-4-[(naphthalen-1-ylsulfonyl)amino]benzoic acid
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
1
3H-benzo[e]indol-2-yl(pyridin-4-yl)methanone
Homo sapiens
above, pH 7.5, 30°C, recombinant GST-tagged enzyme
0.0084
4-(4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-5-bromo-6-oxopyridazin-1(6H)-yl)benzonitrile
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
1
4-bromo-2-phenyl-5-(((tetrahydrofuran-2-yl)methyl)amino)pyridazin-3(2H)-one
Homo sapiens
above, pH 7.5, 30°C, recombinant GST-tagged enzyme
1
4-bromo-2-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridazin-3(2H)-one
Homo sapiens
above, pH 7.5, 30°C, recombinant GST-tagged enzyme
1
4-bromo-5-morpholino-2-phenylpyridazin-3(2H)-one
Homo sapiens
above, pH 7.5, 30°C, recombinant GST-tagged enzyme
0.0034
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzyl-4-bromopyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
10
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one
Homo sapiens
above, pH 7.5, 30°C, recombinant GST-tagged enzyme
0.011
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(3-phenylpropyl)pyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.5
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-((2-(dimethylamino)ethyl)-amino)benzyl)pyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.0091
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-(trifluoromethoxy)phenyl)-pyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.007
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-chlorophenyl)pyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.0087
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-iodobenzyl)pyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.0096
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(pyrimidin-5-yl)pyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.0026
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenethylpyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.0074
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenylpyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.026
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-chloro-2-phenylpyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
1
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-ethoxy-2-phenylpyridazin-3(2H)-one
Homo sapiens
above, pH 7.5, 30°C, recombinant GST-tagged enzyme
0.013
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-iodo-2-phenylpyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
0.5
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-isopropyl-2-phenylpyridazin-3(2H)-one
Homo sapiens
pH 7.5, 30°C, recombinant GST-tagged enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.277
specific PFK-2 activity of the recombinant PFKFB3 protein determined by measurement of fructose 2,6-bisphosphate
additional information
additional information
diet-induced obesity in transgenic mice, liver and plasma metabolites in transgenic and control mice, human Pfkfb3-specific gene probe used to quantify transgene overexpression by RT-PCR, measurement of fructose 2,6-bisphosphate levels in the liver, immunostaining and gene expression analysis in livers of transgenic and control mice, changes in hepatic gene expression profiles for key gluconeogenic and lipogenic enzymes, accumulation of lipids in periportal cells, gain in weight
additional information
expression analysis in different tumor specimens with high and low malignity grade, RT-PCR and Western blot
additional information
expression analysis in different tumor specimens with high and low malignity grade, RT-PCR and Western blot
additional information
expression analysis in different tumor specimens with high and low malignity grade, RT-PCR and Western blot
additional information
expression analysis in different tumor specimens with high and low malignity grade, RT-PCR and Western blot
additional information
proto-oncogenic character of the PFK-2/FBPase-2 of the PFKFB3 gene assumed to play a critical role in tumorigenesis, expression analyzed by RT-PCR and Western blot, expression up-regulated in astrocytomas with high malignity grade
additional information
proto-oncogenic character of the PFK-2/FBPase-2 of the PFKFB3 gene assumed to play a critical role in tumorigenesis, expression analyzed by RT-PCR and Western blot, expression up-regulated in astrocytomas with high malignity grade
additional information
proto-oncogenic character of the PFK-2/FBPase-2 of the PFKFB3 gene assumed to play a critical role in tumorigenesis, expression analyzed by RT-PCR and Western blot, expression up-regulated in astrocytomas with high malignity grade
additional information
proto-oncogenic character of the PFK-2/FBPase-2 of the PFKFB3 gene assumed to play a critical role in tumorigenesis, expression analyzed by RT-PCR and Western blot, expression up-regulated in astrocytomas with high malignity grade
additional information
nuclei isolated from cells transfected with wild type PFKFB3 exhibit 6-phosphofructo-2-kinase activity that is significantly higher than the nuclei obtained from both vector and K472A/K473A-transfected cells
additional information
-
nuclei isolated from cells transfected with wild type PFKFB3 exhibit 6-phosphofructo-2-kinase activity that is significantly higher than the nuclei obtained from both vector and K472A/K473A-transfected cells
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4
SwissProt
isoform PFKFB2, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, EC 2.7.1.105 and EC 3.1.3.46, respectively
SwissProt
isoform PFKFB3, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, EC 2.7.1.105 and EC 3.1.3.46, respectively
SwissProt
isoform PFKFB4, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, EC 2.7.1.105 and EC 3.1.3.46, respectively
SwissProt
Pfkfb3 gene; overexpression of the Pfkfb3 gene in Mus musculus, generation of uPFK-2 transgenic line
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expression analysis in
additional information
40 human astrocytic gliomas and 20 non-neoplastic brain tissue specimens, different malignity grades, expression analysis in
low and high malignancy grades according to histological criteria, expression analysis in
long isozyme variants H1-PFK2, H2-PFK2, and H4-PFK2, and short isozyme variant H3-PFK2
engineered to overexpress PFKFB3, inhibitor studies on recombinant PFKFB3 activity in
overexpression of isozyme PFKFB4. PFKFB4 expression correlates with hypoxia in human lung adenocarcinoma xenografts
increased expression of PFKFB4 in multiple solid tumor types including breast, colon, and prostate
additional information
enzyme PFKFB3 is highly expressed and activated in human cancer cells
additional information
-
enzyme PFKFB3 is highly expressed and activated in human cancer cells
additional information
isozyme PFKFB3 variants are ubiquitously expressed, the variant I-PFK2 is inducible
additional information
isozyme PFKFB3 variants are ubiquitously expressed, the variant I-PFK2 is inducible
additional information
isozyme PFKFB3 variants are ubiquitously expressed, the variant I-PFK2 is inducible
additional information
isozyme PFKFB3 variants are ubiquitously expressed, the variant I-PFK2 is inducible
additional information
isozyme PFKFB4 tissue expression analysis, overview
additional information
PFKFB4 expression is induced in breast, colon, lung, gastric and pancreatic cancer cell lines
additional information
PFKFB4 expression is induced in breast, colon, lung, gastric and pancreatic cancer cell lines
additional information
PFKFB4 expression is induced in breast, colon, lung, gastric and pancreatic cancer cell lines
additional information
PFKFB4 expression is induced in breast, colon, lung, gastric and pancreatic cancer cell lines
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PFKFB3 splice variant 5, the carboxyl terminus is required for this localization
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
Akt inactivation blocks PFKFB2 phosphorylation and fructose 2,6-bisphosphate production
malfunction
knockdown of PFKFB4 in prostate cancer cells increases p62 and reactive oxygen species, but surprisingly increases autophagic flux. Addition of the reactive oxygen species scavenger N-acetyl cysteine prevents p62 accumulation in PFKFB4-depleted cells. PFKFB4 depletion acts upstream of ATG7 consistent with increased oxidative stress that induces autophagy and p62 upregulation
malfunction
PFKFB4 inhibition in H-460 cells reduces glycolytic flux to lactate and glutamate. PFKFB4 inhibition in H-460 cells increases apoptosis under normoxic and hypoxic conditions
malfunction
silencing of PFKFB4 results in increased levels of Fru-2,6-P2 in prostate cancer cells, knockdown of PFKFB4 blocks prostate cancer cell growth and remarkably induced regression of prostate tumor xenografts
malfunction
siRNA silencing of endogenous PFKFB3 inhibits Cdk1 activity, which in turn stabilizes p27 protein levels causing cell cycle arrest at G1/S and increased apoptosis in HeLa cells. PFKFB3 inhibition completely suppresses cell proliferation and results in increased early and late apoptotic cells. PFKFB3 inhibition results in increased nuclear and cytoplasmic p27 protein but has no effect on p57 or p21. Blockade of cell cycle progression and stimulation of apoptosis by PFKFB3 inhibition is mediated by p27
malfunction
enzyme knockdown inhibits clonogenic growth and enhances paclitaxel sensitivity in ovarian and breast cancer cell lines with wild type TP53
metabolism
cancer cells use control of PFKFB3 of the important glycolytic pathway to generate ATP
metabolism
expression level of some PFKFB and PFK1 genes in normoxic and hypoxic conditions in glioma cells is mediated by ERN1 signaling system of endoplasmic reticulum stress. Effect of hypoxia on the expression of genes encoded different 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB1, PFKFB2, PFKFB3 and PFKFB4) and 6-phosphofructo-1-kinase (PFKL, PFKM and PFKP) as well as lactate dehydrogenase in glioma U-87 cells and its subline with suppressed function of ERN1 signaling enzyme, overview
metabolism
expression level of some PFKFB and PFK1 genes in normoxic and hypoxic conditions in glioma cells is mediated by ERN1 signaling system of endoplasmic reticulum stress. Effect of hypoxia on the expression of genes encoded different 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB1, PFKFB2, PFKFB3 and PFKFB4) and 6-phosphofructo-1-kinase (PFKL, PFKM and PFKP) as well as lactate dehydrogenase in glioma U-87 cells and its subline with suppressed function of ERN1 signaling enzyme, overview. Increased expression of PFKFB3 and PFKFB4 under hypoxic conditions correlates with strong induction of PFKL expression in control glioma cells only
metabolism
fructose 2,6-bisphosphate is an important metabolite for the dynamic regulation of glycolytic flux by allosterically activating the rate-limiting enzyme of glycolysis phosphofructokinase-1, fructose 2,6-bisphosphate is a powerful allosteric activator of phosphofructokinase 1, PFK-1
metabolism
the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) comprises well established regulators of glucose metabolism via their synthesis of fructose-2,6 bisphosphate, a potent allosteric activator of 6-phosphofructo-1-kinase. But PFKFB3 and fructose-2,6 bisphosphate function not only as regulators of Pfk-1 but also of Cdk1 activity, and therefore serve to couple glucose metabolism with cell proliferation and survival in transformed cells
metabolism
upregulation of p62 and autophagy is a response to oxidative stress caused by PFKFB4. PFKFB4 is an autophagy regulator
metabolism
enzyme PFKFB3 is an essential target of epidermal growth factor receptor signaling. PFKFB3 activation is required for glycolysis stimulation upon epidermal growth factor receptor activation. PFKFB3 has a key role in mediating glucose metabolism and survival of NSCLC cells in response to epidermal growth factor receptor signaling
metabolism
PFKFB3 has the highest kinase:phosphatase ratio (710:1) to shunt glucose toward glycolysis, whereas PFKFB4 has more fructose-2,6-bisphosphatase-2 activity (kinase:phosphatase ratio of 4.6:1), redirecting glucose toward the pentose phosphate pathway, providing reducing power for lipid biosynthesis and scavenging reactive oxygen species. Co-expression of PFKFB3 and PFKFB4 provides sufficient glucose metabolism to satisfy the bioenergetics demand and redox homeostasis requirements of cancer cells
metabolism
PFKFB3 has the highest kinase:phosphatase ratio (710:1) to shunt glucose toward glycolysis, whereas PFKFB4 has more fructose-2,6-bisphosphatase-2 activity (kinase:phosphatase ratio of 4.6:1), redirecting glucose toward the pentose phosphate pathway, providing reducing power for lipid biosynthesis and scavenging reactive oxygen species. Co-expression of PFKFB3 and PFKFB4 provides sufficient glucose metabolism to satisfy the bioenergetics demand and redox homeostasis requirements of cancer cells. PFKFB4 acts as a protein kinase, regulates steroid receptor coactivator-3 activity and is involved in transcriptional regulation
physiological function
enzyme is required to balance glycolytic activity and antioxidant production to maintain cellular redox balance in prostate cancer cells. Depletion of the enzyme inhibits tumor growth in a xenograft model, indicating that it is required under physiologic nutrient levels. Enzyme mRNA expression is greater in metastatic prostate cancer compared with primary tumors
physiological function
enzyme PFKFB3 belongs to the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFBs) that controls the conversion of fructose-6-phosphate to and from fructose-2,6-bisphosphate, a key regulator of the glycolytic enzyme phosphofructokinase-1
physiological function
in human cancers, loss of PTEN, stabilization of HIF-1alpha and activation of Ras and AKT converge to increase the activity of a key regulator of glycolysis, 6-phosphofructo-2-kinase(PFKFB3). This enzyme synthesizes fructose 2,6-bisphosphate, which is an activator of 6-phosphofructo-1-kinase, a key step of glycolysis
physiological function
isozyme PFKFB4 expressed in multiple transformed cells and tumors functions to synthesize fructose 2,6-bisphosphate, PFKFB4 is required for cancer cell survival during the metabolic response to hypoxia, presumably to enable glycolytic production of ATP when the electron transport chain is not fully operational. Isozyme PFKFB4 is overexpressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines
physiological function
PFKFB3 is overexpressed in human cancers, regulated by HIF-1alpha, Akt and PTEN, and required for the survival and growth of multiple cancer types. Role of PFKFB3 in regulating Cdk1- and p27-mediated G1/S blockade and apoptosis
physiological function
possible role of different isozyme PFKFB4 splice variants in cell-specific and/or tissue-specific regulation of glycolysis, role of PFKFB proteins in the control of cancer metabolism. PFKFB4 may be important for cancer cell survival, PFKFB4 plays an essential role in the survival of glioma stem-like cells and of prostate cancer cells. PFKFB4 is known to be a component of the HIF-mediated response to hypoxia, hypoxic induction of PFKFB4 is mediated by a hypoxia response element (HRE) in the promoter region of the PFKFB4 gene
physiological function
role of PFKFB proteins in the control of cancer metabolism
physiological function
role of PFKFB proteins in the control of cancer metabolism. Liver, muscle and fetal isoform variants of PFKFB1 (L-PFK2, M-PFK2 and F-PFK2 respectively) are transcribed from the same gene, but only L-PFK2 contains a serine residue in position 32 of its C-terminal regulatory domain. This is consistent with its specific physiological role as liver cells need to modulate Fru-2,6-P2 levels to facilitate the production of glucose to fulfill the metabolic demand of other tissues. Response to glucagon, cyclic AMP-dependent protein kinase (PKA) phosphorylates Ser32 in the liver isoform of PFKFB1, leads to inactivation of its PFK-2 activity while activating its FBPase-2 function. This decreases glycolytic flux while increasing gluconeogenesis in liver cells While phosphorylation of L-PFK2 results in a decrease in its kinase activity, phosphorylation of H-PFK2 results in an increase in this activity
physiological function
role of PFKFB proteins in the control of cancer metabolism. PFKFB3 is known to be a component of the HIF-mediated response to hypoxia. PFKFB3 is a hypoxia-inducible gene that is stimulated through the interaction of HIF-1alpha with a consensus HRE within its promoter region
physiological function
the putative autophagy stimulator, isozyme PFKFB4, drives flux through pentose phosphate pathway. PFKFB4 suppresses oxidative stress and p62 accumulation, without which autophagy is stimulated likely as a reactive oxygen species detoxification response. Genes whose loss enhanced p62 elimination are putative negative regulators of autophagy and the bi-functional enzyme PFKFB4 highly inhibits p62 elimination. PFKFB4 is an autophagy regulator. PFKFB4 suppresses autophagy and p62 accumulation by mitigating reactive oxygen species
physiological function
both a PFKFB3 inhibitor or PFKFB3 silencing by siRNA suppress the basal and the H2O2-induced autophagy concomitantly with the inhibition of AMPK activity. Overexpression of wild-type PFKFB3 promotes H2O2-induced autophagy, but mutant K472/473A, which lost nuclear localizing property, inhibits the autophagic process. The K472/473A mutant stimulates more lactate production, and decreases the activity of AMPK compared to the wild-type
physiological function
overexpression of microRNA miR-26b represses PFKFB3 mRNA and protein levels followed by modulation of the expression of glycolytic components such as LDHA, GLUT-1 and markers of invasion and cell cycle such as MMP-9, MMP-2, cyclin D1 and p27. The binding site for miR-26b is predicted in the 3'-untranslated region of the PFKFB3 gene
physiological function
Transforming growth factor TGFbeta1 induces isoform PFKFB3 expression and stimulates glycolysis in Panc1 cells. siRNA silencing of PFKFB3 prevents the stimulation of glycolysis and in vitro invasion ability of Panc1 cells by TGFbeta1. PFKFB3 silencing suppresses the TGFbeta1-mediated induction of the Snail protein
physiological function
tumor suppressor p53 regulates the expression of PFKFB4 and p53-deficient cancer cells are highly dependent on the function of the enzyme. Depletion of PFKFB4 from p53-deficient cancer cells increases levels of fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 is also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Depletion of PFKFB4-attenuates cellular biosynthetic activity and results in the accumulation of reactive oxygen species and cell death in the absence of p53. Silencing of PFKFB4-induces apoptosis in p53-deficient cancer cells in vivo and interferes with tumor growth
physiological function
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2 regulates TP53-dependent paclitaxel sensitivity in ovarian and breast cancers
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). F261_HUMAN
471
0
54681
Swiss-Prot
other Location (Reliability: 5)
F262_HUMAN
505
0
58477
Swiss-Prot
other Location (Reliability: 1)
F263_HUMAN
520
0
59609
Swiss-Prot
other Location (Reliability: 4)
F264_HUMAN
469
0
54040
Swiss-Prot
other Location (Reliability: 4)
Q9H178_HUMAN
92
0
10031
TrEMBL
other Location (Reliability: 2)
Q66S35_HUMAN
462
0
53285
TrEMBL
other Location (Reliability: 4)
Q9BQU2_HUMAN
95
0
10469
TrEMBL
other Location (Reliability: 2)
O60352_HUMAN
176
0
19660
TrEMBL
other Location (Reliability: 3)
Q9UBT0_HUMAN
25
0
2984
TrEMBL
other Location (Reliability: 2)
Q9BQU3_HUMAN
61
0
6393
TrEMBL
other Location (Reliability: 2)
Q9BQU1_HUMAN
31
0
3565
TrEMBL
other Location (Reliability: 2)
Q5XLC3_HUMAN
278
0
32278
TrEMBL
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
58000
additional information
-
primary structures of human, rat and bovine liver enzyme
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
?
x * 58000, long isozyme variants H1-PFK2, H2-PFK2, and H4-PFK2, x * 54000, short isozyme variant H3-PFK2
additional information
domain organization of isozyme PFKFB1 tissue variants, overview
additional information
domain organization of isozyme PFKFB1 tissue variants, overview
additional information
domain organization of isozyme PFKFB1 tissue variants, overview
additional information
domain organization of isozyme PFKFB1 tissue variants, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
side-chain modification
PCAF- and GCN5-mediated acetylation of Lys472/473 disrupts the NLS and sequesters PFKFB3 in the cytoplasm, facilitating its phosphorylation on Ser461 by AMPK. Polyubiquitination on Lys142 of PFKFB3 leads to proteasomal degradation of PFKFB3, shunting glucose metabolism from glycolysis to the PPP. Asymmetrical dimethylation on Arg131 and Arg134 stabilizes PFKFB3. Reduced methylation of PFKFB3 reroutes flux into the oxidative arm of PPP
phosphoprotein
-
phophorylation by cAMP-dependent protein kinase causes activation
phosphoprotein
recombinant His-tagged HBP2, and nontagged wild-type and mutant S460D HBP1 are phosphorylated by several protein kinases, i.e. protein kinases A, B, and C, and by AMP activated kinase, HBP1 mutants are phosphorylated by protein kinase C, overview
phosphoprotein
in response to glucagon, cyclic AMP-dependent protein kinase phosphorylates Ser32 in the liver isoform variant of PFKFB1, leading to inactivation of its PFK-2 activity while activating its FBPase-2 function. Two serine residues, Ser466 and Ser483, within the C-terminal regulatory domain of PFKFB2 can be phosphorylated by protein kinase B (Akt/PKB) in response to insulin
phosphoprotein
specific phosphorylation of heart 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoenzyme PFKFB2 at Ser483. This activation is mediated by the phosphatidylinositol-4,5-bisphosphate 3-kinase and p38 signaling pathways. Amino acid-activated Akt phosphorylates PFKFB2 at Ser483. Akt inactivation blocks PFKFB2 phosphorylation and fructose 2,6-bisphosphate production
phosphoprotein
phosphorylation of Ser461 by AMPK and Thr463 and Ser467 by CDK6 activates 6-phosphofructo-2-kinase activity and promotes glycolysis
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
His-tagged enzyme recombinantly expressed in Escherichia coli, sitting drop vapor diffusion method
the crystal structure of liver enzyme: a head-to-head homodimer, depending on the liganding conditions each subunit contains an ATPgammaS, ADP or P molecule to the kinase domain, and two phosphates, regardless of the liganding conditions, bound to phosphatase domain, structure of enzyme very similar to that of the rat testis isoform
to 2.0 A resolution. Citrate cocrystallizes in the 2-kinase domain, occupying the fructose-6-phosphate binding-site and extending into the gamma-phosphate binding pocket of ATP. In complex with ATP analogue AMPPNP, the presence of a gamma-phosphate makes adoption of the catalytic ATP binding mode impossible for AMPPNP, forcing the analogue to bind atypically with concomitant conformational changes to the ATP binding-pocket
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H253A
site-directed mutagenesis, altered kinetics compared to wild-type enzyme, overview
H253A/S460D
site-directed mutagenesis, altered kinetics compared to wild-type enzyme, overview
K472/473A
mutant fails to localize in nucleus, mainly localizes in cytoplasm. The mutant inhibits the autophagic process, stimulates lactate production, and decreases the activity of AMPK compared to the wild-type
P2R
-
kinetic properties of human liver mutant and rat wild-type enzyme are very similar
S302R
site-directed mutagenesis, altered kinetics compared to wild-type enzyme, overview
S460D
site-directed mutagenesis, altered kinetics compared to wild-type enzyme, overview
S460D/T470D
site-directed mutagenesis, altered kinetics compared to wild-type enzyme, overview
S477D
site-directed mutagenesis, altered kinetics compared to wild-type enzyme, overview
T470D
site-directed mutagenesis, altered kinetics compared to wild-type enzyme, overview
additional information
additional information
construction of a chimeric mutant fusing the N-terminal portion of residues 1-444 of the human enzyme to the C-terminal part, residues 450-530, of the Bos taurus enzyme, i.e. HBPBHP, construction of a deletion mutant lacking the entire carboxyterminal region of residues 446-519
additional information
knockdown of PFKFB4 in prostate cancer cells by specific shRNA targeting
additional information
siRNA silencing of endogenous PFKFB3 in HeLa cells by siRNA
additional information
-
siRNA silencing of endogenous PFKFB3 in HeLa cells by siRNA
additional information
stable shRNA knockdown of PFKFB4, silencing by siRNA and genomic deletion of PFKFB4 decrease fructose 2,6-bisphosphate. PFKFB4 overexpression increases fructose 2,6-bisphosphate and selective PFKFB4 inhibition in vivo markedly reduces fructose 2,6-bisphosphate, glucose uptake, and ATP levels
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged isozyme PFKFB3 from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
recombinant His6-tagged enzyme variants HBP1 and HBP2 and of mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity and ion exchange chromatography, the tag is cleaved off, recombinant enzyme form HBP1 partially from Sf9 insect cells by affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
both parent and double mutant (K472A/K473A) constructs are transformed into the BL21 strain of Escherichia coli, overexpression of PFKFB3 causes no change in glucose metabolism but rather a marked increase in cell proliferation
expressed in Escherichia coli, overexpression under the control of the phosphoenolpyruvate carboxykinase promoter in Mus musculus, microinjection of fertilized eggs, C57BL56/SJL receptor females of Mus musculus implanted with microinjected oocytes
gene PFKFB1, located on chromosome Xp11.21, the PFKFB1 gene contains 17 exons and encodes 3 different mRNAs L, M and F
gene PFKFB2, located on chromosome 1q31, encodes the heart isozyme, the PFKFB2 gene encodes four different mRNAs that are derived from different promoters and that vary only in non-coding sequences at the 5'-end
gene PFKFB3, located on chromosome 10p14-p15, gene PFKFB3 contains at least 19 exons and generates at least 6 different transcripts by alternative splicing. The resulting polypeptides differ in the length of their C-terminal variable regions that are encoded by the last seven exons. Alternative splicing of exon 15 generates the two main isoforms that differ by a short C-terminal sequence: the ubiquitous PFK2 (U-PFK2, 15 exons) and the inducible PFK2 (I-PFK2, 16 exons) isoforms
gene PFKFB3, recombinant expression of GST-tagged isozyme PFKFB3 in Escherichia coli strain BL21(DE3)
gene PFKFB4, located on chromosome 3p21-p22, the gene contains at least 14 exons, and several splice variants of the PFKFB4 mRNA
isoform of enzyme that is induced by proinflammatory stimuli and that is distinguished by the presence of multiple copies of the AUUUA instability motif in its 3' untranslated region is identified and the complete cDNA is cloned and sequenced, expression in eigth human tumor cell lines
subcloned into the pET-30b(+) vector, expression in BL21 (DE3) Escherichia coli
subcloning and overexpression of 2 brain enzyme variants HBP1 and HBP2 and of mutant enzymes as His6-tagged proteins in Escherichia coli, expression of enzyme form HBP1 in Spodoptera frugiperda Sf9 insect cells via baculovirus infection system
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
bifunctional 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 mRNA expression is greater in metastatic prostate cancer compared with primary tumors
blocking the function of ERN1 enzyme, the key endoplasmic reticulum stress sensor, leads to an increase in the expression levels of PFKFB1, PFKFB2, PFKFB3 and PFKFB4 mRNA, being more significant for PFKFB4 and PFKFB2
blocking the function of ERN1 enzyme, the key endoplasmic reticulum stress sensor, leads to an increase in the expression levels of PFKFB1, PFKFB2, PFKFB3 and PFKFB4 mRNA, being more significant for PFKFB4 and PFKFB2. Hypoxic conditions leads to an increase of the expression level of PFKFB3 and PFKFB4 mRNA both in control glioma cells and cells with ERN1 loss of function, being more significant for PFKFB4. The blockade of ERN1 signaling enzyme function decreases the effect of hypoxia on the expression level of both PFKFB3 and PFKFB4 mRN
ectopic expression of wild type PFKFB3 increases phosphorylation of the cell cycle inhibitor p27, a member of the Kip/Cip family of proteins and a universal inhibitor of cyclin-dependent kinases and the cell cycle, at threonine 187 and decreases total p27 protein levels
enzyme expression in esophageal squamous cell carcinoma cell is significantly higher than in adjacent non-tumor tissues
ERN1 loss of function and hypoxic conditions do not affect PFKFB1 mRNA levels
hypoxic conditions do not affect PFKFB2 mRNA levels
in cells with ERN1 loss of function decreases PFKFB2 mRNA
p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases
PFKFB3 is the major 6-phosphofructo-2-kinase isozymes overexpressed in human cancers
PFKFB4 is the major 6-phosphofructo-2-kinase isozymes overexpressed in human cancers
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
isozyme PFKFB4 appears to be a rational target for anti-neoplastic drug development
medicine
pharmacology
role of PFKFB3 protein in tumorigenesis, expression studies in human astrocytic gliomas of different malignancy grades
medicine
a molecule in which EDTA is covalently linked to ADP is a good starting molecule for the development of new cancer-therapeutic molecules
medicine
-
the key role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in neoplastic transformation provides a rational for the development of agents that selectively inhibit the PFKFB3 enzyme as antineoplastic agents
medicine
-
the pharmacologic inhibition of this enzyme may effect the survival and growth of neoplastic cells
medicine
clinical development of PFKFB3 inhibitors as chemotherapeutic agents
medicine
bifunctional 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 mRNA expression is greater in metastatic prostate cancer compared with primary tumors
medicine
pharmacological disruption of the PFKFB4 kinase domain may have clinical utility for the treatment of human cancers
medicine
PFK-2/FBPase-2 enzymes is attractive targets for cancer treatment
medicine
in colonic and bladder cancer cells, additive growth inhibitory effects are seen with phenformin and with an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3. The increased acidification of the culture medium and glucose uptake caused by phenformin is blocked by combined treatment with PFKFB3 inhibitors
medicine
tumor suppressor p53 regulates the expression of PFKFB4 and p53-deficient cancer cells are highly dependent on the function of the enzyme. Depletion of PFKFB4 from p53-deficient cancer cells increases levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 is also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Depletion of PFKFB4-attenuated cellular biosynthetic activity and results in the accumulation of reactive oxygen species and cell death in the absence of p53. Silencing of PFKFB4-induces apoptosis in p53-deficient cancer cells in vivo and interferes with tumor growth
medicine
chemical enzyme PFKFB3 inhibition synergizes with erlotinib in increasing erlotinib s antiproliferative activity in NSCLC cells
medicine
enzyme inhibition can enhance the effect of paclitaxel-based primary chemotherapy upon ovarian and breast cancers retaining wild type TP53
medicine
high PFKFB3 protein and gene expression may be associated with the occurrence, development, and prognosis of esophageal squamous cell carcinoma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sakakibara, R.; Uemura, M.; Hirata, T.; Okamura, N.; Kato, M.
Human placental fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase: its isozymic form, expression and characterization
Biosci. Biotechnol. Biochem.
61
1949-1952
1997
Homo sapiens
Sakakibara, R.; Kato, M.; Okamura, N.; Nakagawa, T.; Komada, Y.; Tominaga, N.; Shimojo, M.; Fukasawa, M.
Characterization of a human placental fructose-6-phosphate,2-kinase fructose-2,6-bisphosphatase
J. Biochem.
122
122-128
1997
Homo sapiens
Lange, A.J.; Li, L.; Vargas, A.M.; Pilkis, S.J.
Expression of human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Escherichia coli. Role of N-2 proline in degradation of the protein
J. Biol. Chem.
268
8078-8084
1993
Homo sapiens, Rattus norvegicus
Lee, Y.H.; Li, Y.; Uyeda, K.; Hasemann, C.A.
Tissue-specific structure/function differentiation of the liver isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
J. Biol. Chem.
278
523-530
2003
Homo sapiens (P16118)
Sakakibara, R.; Okudaira, T.; Fujiwara, K.; Kato, M.; Hirata, T.; Yamanaka, S.; Naito, M.; Fukasawa, M.
Tissue distribution of placenta-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
Biochem. Biophys. Res. Commun.
257
177-181
1999
Homo sapiens, Rattus norvegicus
Chesney, J.; Mitchell, R.; Benigni, F.; Bacher, M.; Spiegel, L.; Al-Abed, Y.; Han, J.H.; Metz, C.; Bucala, R.
An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect
Proc. Natl. Acad. Sci. USA
96
3047-3052
1999
Faxonius limosus, Homo sapiens (Q16875), Homo sapiens
Manes, N.P.; El-Maghrabi, M.R.
The kinase activity of human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is regulated via inhibition by phosphoenolpyruvate
Arch. Biochem. Biophys.
438
125-136
2005
Homo sapiens (Q16875)
Kim, S.G.; Manes, N.P.; El-Maghrabi, M.R.; Lee, Y.H.
Crystal structure of the hypoxia-inducible form of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3): a possible new target for cancer therapy
J. Biol. Chem.
281
2939-2944
2006
Homo sapiens (P16118), Homo sapiens
Mouton, V.; Vertommen, D.; Bertrand, L.; Hue, L.; Rider, M.H.
Evaluation of the role of protein kinase Czeta in insulin-induced heat 6-phosphofructo-2-kinase activation
Cell. Signal.
19
52-61
2007
Homo sapiens
Chesney, J.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis
Curr. Opin. Clin. Nutr. Metab. Care
9
535-539
2006
Homo sapiens
Telang, S.; Yalcin, A.; Clem, A.L.; Bucala, R.; Lane, A.N.; Eaton, J.W.; Chesney, J.
Ras transformation requires metabolic control by 6-phosphofructo-2-kinase
Oncogene
25
7225-7234
2006
Homo sapiens, Mus musculus
Kessler, R.; Bleichert, F.; Warnke, J.P.; Eschrich, K.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is up-regulated in high-grade astrocytomas
J. Neurooncol.
86
257-264
2008
Homo sapiens (O60825), Homo sapiens (P16118), Homo sapiens (Q16875), Homo sapiens (Q16877)
Duran, J.; Navarro-Sabate, A.; Pujol, A.; Perales, J.C.; Manzano, A.; Obach, M.; Gomez, M.; Bartrons, R.
Overexpression of ubiquitous 6-phosphofructo-2-kinase in the liver of transgenic mice results in weight gain
Biochem. Biophys. Res. Commun.
365
291-297
2008
Homo sapiens (Q16875)
Clem, B.; Telang, S.; Clem, A.; Yalcin, A.; Meier, J.; Simmons, A.; Rasku, M.A.; Arumugam, S.; Dean, W.L.; Eaton, J.; Lane, A.; Trent, J.O.; Chesney, J.
Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth
Mol. Cancer Ther.
7
110-120
2008
Homo sapiens (Q16875), Homo sapiens
Yalcin, A.; Clem, B.F.; Simmons, A.; Lane, A.; Nelson, K.; Clem, A.L.; Brock, E.; Siow, D.; Wattenberg, B.; Telang, S.; Chesney, J.
Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases
J. Biol. Chem.
284
24223-24232
2009
Homo sapiens (Q16875), Homo sapiens
Ros, S.; Santos, C.R.; Moco, S.; Baenke, F.; Kelly, G.; Howell, M.; Zamboni, N.; Schulze, A.
Functional metabolic screen identifies 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 as an important regulator of prostate cancer cell survival
Cancer Discov.
2
328-343
2012
Homo sapiens (Q16877)
Brooke, D.G.; van Dam, E.M.; Watts, C.K.; Khoury, A.; Dziadek, M.A.; Brooks, H.; Graham, L.J.; Flanagan, J.U.; Denny, W.A.
Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3)
Bioorg. Med. Chem.
22
1029-1039
2014
Homo sapiens (Q16875)
Novellasdemunt, L.; Tato, I.; Navarro-Sabate, A.; Ruiz-Meana, M.; Mendez-Lucas, A.; Perales, J.C.; Garcia-Dorado, D.; Ventura, F.; Bartrons, R.; Rosa, J.L.
Akt-dependent activation of the heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) isoenzyme by amino acids
J. Biol. Chem.
288
10640-10651
2013
Homo sapiens (O60825), Homo sapiens, Rattus norvegicus (Q9JJH5), Rattus norvegicus Sprague-Dawley (Q9JJH5)
Chesney, J.; Clark, J.; Klarer, A.C.; Imbert-Fernandez, Y.; Lane, A.N.; Telang, S.
Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is required for the glycolytic response to hypoxia and tumor growth
Oncotarget
5
6670-6686
2014
Homo sapiens (Q16877)
Ros, S.; Schulze, A.
Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism
Cancer Metab.
1
8
2013
Homo sapiens (O60825), Homo sapiens (P16118), Homo sapiens (Q16875), Homo sapiens (Q16877)
Klarer, A.C.; ONeal, J.; Imbert-Fernandez, Y.; Clem, A.; Ellis, S.R.; Clark, J.; Clem, B.; Chesney, J.; Telang, S.
Inhibition of 6-phosphofructo-2-kinase (PFKFB3) induces autophagy as a survival mechanism
Cancer Metab.
2
2
2014
Homo sapiens (Q16875), Homo sapiens
Yalcin, A.; Clem, B.F.; Imbert-Fernandez, Y.; Ozcan, S.C.; Peker, S.; ONeal, J.; Klarer, A.C.; Clem, A.L.; Telang, S.; Chesney, J.
6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27
Cell Death Dis.
5
e1337
2014
Homo sapiens (Q16875), Homo sapiens
Clem, B.F.; ONeal, J.; Tapolsky, G.; Clem, A.L.; Imbert-Fernandez, Y.; Kerr, D.A.; Klarer, A.C.; Redman, R.; Miller, D.M.; Trent, J.O.; Telang, S.; Chesney, J.
Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer
Mol. Cancer Ther.
12
1461-1470
2013
Homo sapiens (Q16875), Homo sapiens
Strohecker, A.M.; Joshi, S.; Possemato, R.; Abraham, R.T.; Sabatini, D.M.; White, E.
Identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel autophagy regulator by high content shRNA screening
Oncogene
34
5662-5676
2015
Homo sapiens (Q16877)
Minchenko, D.; Lypova, N.; Harmash, Y.; Kulinich, A.; Marunych, R.; Karbovskyi, L.; Minchenko, O.
Expression of genes encoded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and 6-phosphofructo-1-kinase in U87 glioma cells with ERN1 loss of function: hypoxic regulation
Res. J. Pharm. Biol. Chem. Sci.
4
28-42
2013
Homo sapiens (O60825), Homo sapiens (P16118), Homo sapiens (Q16875), Homo sapiens (Q16877)
-
Lea, M.A.; Guzman, Y.; Desbordes, C.
Inhibition of growth by combined treatment with inhibitors of lactate dehydrogenase and either phenformin or inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
Anticancer Res.
36
1479-1488
2016
Homo sapiens (Q16875)
Yalcin, A.; Solakoglu, T.H.; Ozcan, S.C.; Guzel, S.; Peker, S.; Celikler, S.; Balaban, B.D.; Sevinc, E.; Gurpinar, Y.; Chesney, J.A.
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor beta1-enhanced invasion of Panc1 cells invitro
Biochem. Biophys. Res. Commun.
484
687-693
2017
Homo sapiens (Q16875)
Ros, S.; Floeter, J.; Kaymak, I.; Da Costa, C.; Houddane, A.; Dubuis, S.; Griffiths, B.; Mitter, R.; Walz, S.; Blake, S.; Behrens, A.; Brindle, K.M.; Zamboni, N.; Rider, M.H.; Schulze, A.
6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells
Oncogene
36
3287-3299
2017
Homo sapiens (Q16877)
Du, J.Y.; Wang, L.F.; Wang, Q.; Yu, L.D.
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
Oncol. Rep.
33
1890-1898
2015
Homo sapiens (Q16875)
Yan, S.; Wei, X.; Xu, S.; Sun, H.; Wang, W.; Liu, L.; Jiang, X.; Zhang, Y.; Che, Y.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 spatially mediates autophagy through the AMPK signaling pathway
Oncotarget
8
80909-80922
2017
Homo sapiens (Q16875)
Crochet, R.; Kim, J.; Lee, H.; Yim, Y.; Kim, S.; Neau, D.; Lee, Y.
Crystal structure of heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) and the inhibitory influence of citrate on substrate binding
Proteins
85
117-124
2017
Homo sapiens (O60825), Bos taurus (P26285)
Langer, S.; Hofmeister-Brix, A.; Waterstradt, R.; Baltrusch, S.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and small chemical activators affect enzyme activity of activating glucokinase mutants by distinct mechanisms
Biochem. Pharmacol.
168
149-161
2019
Homo sapiens (O60825)
Yang, H.; Shu, Z.; Jiang, Y.; Mao, W.; Pang, L.; Redwood, A.; Jeter-Jones, S.L.; Jennings, N.B.; Ornelas, A.; Zhou, J.; Rodriguez-Aguayo, C.; Bartholomeusz, G.; Iles, L.R.; Zacharias, N.M.; Millward, S.W.; Lopez-Berestein, G.; Le, X.F.; Ahmed, A.A.; Piwnica-Worms, H.; Sood, A.K.; Bast, R.C.; Lu, Z.
6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase-2 regulates TP53-dependent paclitaxel sensitivity in ovarian and breast cancers
Clin. Cancer Res.
25
5702-5716
2019
Homo sapiens (O60825)
Emini Veseli, B.; Perrotta, P.; Van Wielendaele, P.; Lambeir, A.M.; Abdali, A.; Bellosta, S.; Monaco, G.; Bultynck, G.; Martinet, W.; De Meyer, G.R.Y.
Small molecule 3PO inhibits glycolysis but does not bind to 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3)
FEBS Lett.
594
3067-3075
2020
Homo sapiens (Q16875)
Lypova, N.; Telang, S.; Chesney, J.; Imbert-Fernandez, Y.
Increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity in response to EGFR signaling contributes to non-small cell lung cancer cell survival
J. Biol. Chem.
294
10530-10543
2019
Homo sapiens (Q16875)
Bao, J.; Wu, Y.; Wang, L.; Zhu, Y.
The role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 in esophageal squamous cell carcinoma
Medicine (Baltimore)
99
e19626
2020
Homo sapiens (Q16875)
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