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Information on EC 2.7.1.105 - 6-phosphofructo-2-kinase and Organism(s) Mus musculus and UniProt Accession P70265
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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
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fru-6-p
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3-3hglucose
- fbpase-2
- pharmacology
- diagnostics
- drug development
The taxonomic range for the selected organisms is: Mus musculus
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
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6-phosphofructose 2-kinase
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-
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ATP:D-fructose-6-phosphate 2-phosphotransferase
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fructose 6-phosphate 2-kinase
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iPFK2
kinase, 6-phosphofructo-2-(phosphorylating)
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phosphofructokinase 2
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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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
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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
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-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
transgene causes changes in cardiac metabolite concentrations, increased glycolysis, reduced palmitate oxidation, protection from hypoxia
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-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
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-
-
r
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
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-
-
?
additional information
?
-
-
also catalyses the degradation of fructose 2,6-bisphosphate (EC 3.1.3.46)
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-
?
additional information
?
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the expression of the inducible PFK2/FBPase is selectively necessary for the control of glycolytic flux in cells transformed with ras
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?
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
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-
-
?
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
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-
-
?
additional information
?
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the expression of the inducible PFK2/FBPase is selectively necessary for the control of glycolytic flux in cells transformed with ras
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-bromoacetylethanolamine
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repetitive administration affects inhibition of glycolysis and lipid metabolism, causing suppression of body weight gain
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
generation of transgenic mice with chronically elevated glycolysis by cardiac-specific overexpression of PFK-2, measurements of metabolites reveal 3fold elevated levels of fructose 2,6-bisphosphate, expression studies by real-time PCR and Western blot analysis, transgene causes significant increase in glycolysis providing acute benefits against hypoxia
additional information
identification and expression of alternative splice variants in different tissue under hypoxia, splice variants different at C-terminal region but catalytical domains of 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase identical, tissue-specific expression, different induction under hypoxic conditions, role of splice isoforms in cell adaptation to hypoxic conditions discussed
additional information
identification and expression of alternative splice variants in different tissue under hypoxia, splice variants different at C-terminal region but catalytical domains of 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase identical, tissue-specific expression, different induction under hypoxic conditions, role of splice isoforms in cell adaptation to hypoxic conditions discussed
additional information
A7UAK6
identification and expression of alternative splice variants in different tissue under hypoxia, splice variants different at C-terminal region but catalytical domains of 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase identical, tissue-specific expression, different induction under hypoxic conditions, role of splice isoforms in cell adaptation to hypoxic conditions discussed
additional information
-
identification and expression of alternative splice variants in different tissue under hypoxia, splice variants different at C-terminal region but catalytical domains of 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase identical, tissue-specific expression, different induction under hypoxic conditions, role of splice isoforms in cell adaptation to hypoxic conditions discussed
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
under hypoxia, expression analysis of alternative splice variants in
under hypoxia, expression analysis of alternative splice variants in
under hypoxia, expression analysis of alternative splice variants in
expressed at high abundance in both hypothalami and clonal hypothalamic neurons. In response to re-feeding, isoform PFKFB3 mRNA levels are increased by 10fold in mouse hypothalami
expressed at high abundance in both hypothalami and clonal hypothalamic neurons
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
Mb transgenic mice have reduced fructose 2,6-bisphosphate levels, due to cardiac expression of a transgene for a mutant, kinase deficient form of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) which controls the level of fructose 2,6-bisphosphate. Mb hearts are markedly more sensitive to transverse aortic constriction-induced damage showing lower fractional shortening in Mb-TAC mice as well as larger left ventricular end diastolic and end systolic diameters. Cardiac hypertrophy and pulmonary congestion are more severe in Mb-transverse aortic constriction mice, Mb transgene exacerbates transverse aortic constriction-induced increases in cardiac hypertrophy and lung weight, detailed phenotype, overview
physiological function
fructose 2,6-bisphosphate is a positive regulator of the glycolytic enzyme phosphofructokinase
malfunction
knockdown of PFKFB3/iPFK2 in N-43/5 neurons causes a decrease in rates of glycolysis, which is accompanied by increased AMPK phosphorylation, increased AgRP mRNA levels and decreased CART mRNA levels. Overexpression of PFKFB3/iPFK2 in N-43/5 neurons causes an increase in glycolysis, which is accompanied by decreased AMPK phosphorylation and decreased AgRP mRNA levels and increased CART mRNA levels
metabolism
physiological function
metabolism
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moderate grade hyperammonemia activates lactate dehydrogenase-4 and 6-phosphofructo-2-kinase to support increased lactate turnover in the brain slices
metabolism
re-feeding increases plasma levels of glucose and insulin and stimulates PFKFB3 expression. Glucose and insulin stimulate PFKFB3 expression, increase glycolysis, and decrease AMPK phosphorylation in clonal hypothalamic neurons
physiological function
knockdown of isoform PFKFB3/iPFK2 in N-43/5 neurons causes a decrease in rates of glycolysis, which is accompanied by increased AMP-activated protein kinase phosphorylation, increased agouti-related protein mRNA levels and decreased cocaine-amphetamine-related transcript mRNA levels. Overexpression of PFKFB3/iPFK2 in N-43/5 neurons causes an increase in glycolysis, which is accompanied by decreased AMP-activated protein kinase phosphorylation and decreased agouti-related protein mRNA levels and increased cocaine-amphetamine-related transcript mRNA levels
physiological function
role for PFKFB3/iPFK2 in regulating glycolysis in hypothalamic neurons, in the context of neuronal glucose sensing and neuropeptide expression. PFKFB3/iPFK2 responds to re-feeding, which in turn stimulates hypothalamic glycolysis and decreases hypothalamic AMPK phosphorylation and alters neuropeptide expression in a pattern that is associated with suppression of food intake
physiological function
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the PFK2 domain of PFK2/FBPase2 regulates glycolysis to maintain the pyruvate pool for lactate synthesis
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). F262_MOUSE
519
0
59925
Swiss-Prot
other Location (Reliability: 2)
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
re-feeding increases plasma levels of glucose and insulin and stimulates PFKFB3 expression. Glucose and insulin stimulate PFKFB3 expression, increase glycolysis, and decrease AMPK phosphorylation in clonal hypothalamic neurons
the PFK2 expression is increased about 2fold in 0.5 mM ammonia treated brain slices
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upon re-feeding, isoform PFKFB3 mRNA levels are increased by 10fold in mouse hypothalami
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
analysis of increase in cardiac glycolysis during ischemia and heart failure
diagnostics
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the level of PFK2 is considered as a marker of glycolytic activation at tissue level
medicine
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the pharmacologic inhibition of this enzyme may effect the survival and growth of neoplastic cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Harada, Y.; Tominaga, N.; Watanabe, M.; Shimokawa, R.; Ishiguro, M.; Sakakibara, R.
Inhibition of fructose-6-phosphate,2-kinase by N-bromoacetylethanolamine phosphate in vitro and in vivo
J. Biochem.
121
724-730
1997
Mus musculus, Rattus norvegicus
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
Wang, Q.; Donthi, R.V.; Wang, J.; Lange, A.J.; Watson, L.J.; Jones, S.P.; Epstein, P.N.
Cardiac phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase increases glycolysis, hypertrophy, and myocyte resistance to hypoxia
Am. J. Physiol. Heart Circ. Physiol.
294
H2889-H2897
2008
Mus musculus (P70265)
Mykhalchenko, V.G.; Minchenko, D.O.; Tsuchihara, K.; Moenner, M.; Komisarenko, S.V.; Bikfalvi, A.; Esumi, H.; Minchenko, O.H.
Expression of mouse 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 mRNA alternative splice variants in hypoxia
Ukr. Biokhim. Zh.
80
19-25
2008
Rattus norvegicus (A7UAK3), Mus musculus (A7UAK4), Mus musculus (A7UAK5), Mus musculus (A7UAK6), Mus musculus
Li, H.; Guo, X.; Xu, H.; Woo, S.; Halim, V.; Morgan, C.; Wu, C.
A role for inducible 6-phosphofructo-2-kinase in the control of neuronal glycolysis
J. Nutr. Biochem.
24
:1153-1158
2012
Mus musculus (Q7TS91), Mus musculus
Li, H.; Guo, X.; Xu, H.; Woo, S.; Halim, V.; Morgan, C.; Wu, C.
A role for inducible 6-phosphofructo-2-kinase in the control of neuronal glycolysis
J. Nutr. Biochem.
24
1153-1158
2013
Mus musculus (A7UAK5), Mus musculus, Mus musculus C57/BL6J (A7UAK5)
Mehrotra, A.; Trigun, S.K.
Moderate grade hyperammonemia activates lactate dehydrogenase-4 and 6-phosphofructo-2-kinase to support increased lactate turnover in the brain slices
Mol. Cell. Biochem.
381
157-161
2013
Mus musculus
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