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Information on EC 3.1.3.46 - fructose-2,6-bisphosphate 2-phosphatase and Organism(s) Mus musculus
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3.1.3.46 fructose-2,6-bisphosphate 2-phosphataseIUBMB Comments
The enzyme copurifies with EC 2.7.1.105 6-phosphofructo-2-kinase. (cf. EC 3.1.3.54 fructose-2,6-bisphosphate 6-phosphatase).
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Word Map
- 3.1.3.46
- fructose-1,6-bisphosphatase
-
gluconeogenesis
-
gluconeogenic
- amp
- 6-phosphate
-
1,6-bisphosphatase
-
tp53-induced
- phosphoenolpyruvate
- isozyme
- chloroplast
- endothelial
- glycogen
- pentose
- 6-phosphofructo-1-kinase
- hepatocytes
-
carboxykinase
- fructose-6-phosphate
-
hypoxia-inducible
- glucokinase
-
camp-dependent
-
warburg
- pepck
-
3.1.3.11
-
glucose-induced
- g6pase
- spinach
- hk2
-
fructose-1
- hypoglycemia
- glucose-6-phosphatase
- hexokinase
-
fru-6-p
-
glycogenolysis
-
calvin
-
p53-inducible
-
anaphase-promoting
- phosphofructokinase-1
- phosphoenzyme
-
fructose-6-p
- molecular biology
- medicine
- pharmacology
- agriculture
-
pentose-phosphate
-
z-line
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
fbpase, pfkfb3, tigar, pfk-2, pfkfb4, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, fructose-2,6-bisphosphatase, pfkfb2, pfk-2/fbpase-2, f-2,6-p2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
D-fructose-2,6-bisphosphatase
-
-
-
-
FBPase-2
fructose-2,6-bisphosphatase
fructose-2,6-diphosphatase
-
-
-
-
PFKFB-3
isoform, bifunctional enzyme possessing 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities
phosphatase, fructose 2,6-di-
-
-
-
-
additional information
fructose-2,6-bisphosphatase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
beta-D-fructose 2,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate
FBPase performs a reaction following a classical ping pong mechanism with formation of a phosphoryl-enzyme intermediate on a histidine residue located in an Arg-His-Gly triad, catalytic site structure, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
beta-D-fructose-2,6-bisphosphate 2-phosphohydrolase
The enzyme copurifies with EC 2.7.1.105 6-phosphofructo-2-kinase. (cf. EC 3.1.3.54 fructose-2,6-bisphosphate 6-phosphatase).
CAS REGISTRY NUMBER
COMMENTARY
81611-75-8
-
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
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
-
-
-
-
?
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
-
-
-
?
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
metabolic regulation of isozyme PFKFB2
-
-
?
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
metabolic regulation of isozyme PFKFB3
-
-
?
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
-
the bifunctional enzyme is responsible for regulation of intracellular beta-D-fructose 2,6-bisphosphate level, isozyme PFKFB3 mediates beta-D-fructose 2,6-bisphosphate production in proliferating cells, isozyme roles in glycolysis regulation in adipocytes, overview
-
-
?
additional information
?
-
-
enzyme expression is highly reduced in diabetic mice, insulin is required for enzyme induction/regulation, a high enzyme expression level reduces blood glucose level and increases the expression of glucokinase, metabolic regulation overview
-
-
?
additional information
?
-
-
PFKFB3 overexpression increases the glycolysis level
-
-
?
additional information
?
-
-
the enzyme rather than its substrate fructose 2,6-bisphosphate is crucial in glucose-induced insulin secretion through regulation of glucokinase activity or subcellular targeting
-
-
?
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
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
-
-
-
-
?
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
metabolic regulation of isozyme PFKFB2
-
-
?
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
metabolic regulation of isozyme PFKFB3
-
-
?
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
-
the bifunctional enzyme is responsible for regulation of intracellular beta-D-fructose 2,6-bisphosphate level, isozyme PFKFB3 mediates beta-D-fructose 2,6-bisphosphate production in proliferating cells, isozyme roles in glycolysis regulation in adipocytes, overview
-
-
?
additional information
?
-
-
enzyme expression is highly reduced in diabetic mice, insulin is required for enzyme induction/regulation, a high enzyme expression level reduces blood glucose level and increases the expression of glucokinase, metabolic regulation overview
-
-
?
additional information
?
-
-
PFKFB3 overexpression increases the glycolysis level
-
-
?
additional information
?
-
-
the enzyme rather than its substrate fructose 2,6-bisphosphate is crucial in glucose-induced insulin secretion through regulation of glucokinase activity or subcellular targeting
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
expression of isozyme PFKFB3 is reduced by prolonged treatment of 3T3-L1 cells with insulin
-
additional information
-
streptozotocin highly reduces enzyme expression, treated mice show undetecable low levels of insulin, the effect is reversible by application of insulin
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
the hepatic enzyme expression is stimulated at transcriptional level by both insulin and glucocorticoids
-
additional information
significant increase of the expression of PFKFB-3 mRNA is observed in the mouse lungs, testes and brain in hypoxia
-
additional information
-
significant increase of the expression of PFKFB-3 mRNA is observed in the mouse lungs, testes and brain in hypoxia
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
tissue-specific expression of the different isozymes, overview
additional information
tissue-specific expression of the different isozymes, overview
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
flux through phosphofructokinase-1 is controlled by the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 via production/degradation of fructose-2,6-bisphosphate, a potent allosteric activator of phosphofructokinase-1, as well as direct activation of glucokinase due to a protein-protein interaction
physiological function
physiological function
-
PFK2/FBPase2 is most helpful to the glucose-sensing capacity of glucokinase in a fasted organism, or in the transition to threshold as glucose is elevated during feeding
physiological function
TIGAR potently inhibits NF-kappaB-dependent gene expression by suppressing the upstream activation of IKKbeta phosphorylation and kinase activation. Inhibition occurs through a direct binding competition between NEMO and TIGAR for association with the linear ubiquitination assembly complex LUBAC. A TIGAR phosphatase activity-deficient mutant is equally effective as wild-type TIGAR in inhibiting NEMO linear ubiquitination. TIGAR knockout mice display enhanced adipose tissue NF-kappaB signaling, and adipocyte-specific overexpression of TIGAR suppresses adipose tissue NF-kappaB signaling
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). TIGAR_MOUSE
269
0
29191
Swiss-Prot
other Location (Reliability: 3)
F261_MOUSE
471
0
54849
Swiss-Prot
Mitochondrion (Reliability: 4)
F262_MOUSE
519
0
59925
Swiss-Prot
other Location (Reliability: 2)
F264_MOUSE
469
0
54067
Swiss-Prot
other Location (Reliability: 4)
A2AUP5_MOUSE
514
0
58967
TrEMBL
other Location (Reliability: 4)
A7UAK8_MOUSE
543
0
62201
TrEMBL
other Location (Reliability: 4)
C9VZF1_MOUSE
415
0
47921
TrEMBL
other Location (Reliability: 4)
Q3U3S6_MOUSE
549
0
62906
TrEMBL
other Location (Reliability: 4)
C9VZF2_MOUSE
435
0
50246
TrEMBL
other Location (Reliability: 4)
B0FLL3_MOUSE
102
0
11434
TrEMBL
other Location (Reliability: 1)
A7UAK4_MOUSE
462
0
53481
TrEMBL
other Location (Reliability: 4)
A7UAK5_MOUSE
555
0
63653
TrEMBL
other Location (Reliability: 4)
C9VZF3_MOUSE
330
0
38219
TrEMBL
other Location (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
head-to-head structure of the two subunits of the bifunctional enzyme, overview
additional information
head-to-head structure of the two subunits of the bifunctional enzyme, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
cardiac expression of kinase-deficient enzyme in amyocyte cell line inhibits glycolysis, promotes hypertrophy, impairs myocyte function, and reduces insulin sensitivity
additional information
-
PFKFB3 overexpression increases the glycolysis level in recombinant COS-7 cells
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in MIN-6 cell by incubation for 2h with increasing titres of adenoviral vectors
-
expression of wild-type and mutant PFK-2 in 6-phosphofructo-2-kinase-deficient myocytes
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isozyme PFKFB3 from 3T3-L1 adipocytes, expression and splicing analysis, overview, expression as His-tagged enzyme in Escherichia coli, expression of His-tagged enzyme in COS-7 cells
-
overexpression of hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphate using an adenoviral vector
-
phylogenetic analysis, transcriptional control of isozymes, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
-
overexpression alone has negligible effects on insulin secretion, only in combination with 6-phosphofructo-2-kinase, partial down-regulation of endogenous PFKFB2 and PFKFB3 in INS1 cells by siRNA decreased PFK-2/FBPase-2 protein, fructose 2,6-bisphosphate content, glucokinase activity and glucose-induced insulin secretion
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rider, M.H.; Bertrand, L.; Vertommen, D.; Michels, P.A.; Rousseau, G.G.; Hue, L.
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis
Biochem. J.
381
561-579
2004
Arabidopsis thaliana (Q9MB58), Bos taurus (P26285), Bos taurus (P49872), Bos taurus (Q28901), Desulfovibrio desulfuricans, Drosophila melanogaster (Q9VWH7), Homo sapiens (O60825), Homo sapiens (P16118), Homo sapiens (Q16875), Homo sapiens (Q16877), Leishmania major, Mus musculus (P70265), Mus musculus (Q9ESY2), Rattus norvegicus (O35552), Rattus norvegicus (P07953), Rattus norvegicus (P25114), Rattus norvegicus (Q9JJH5), Schizosaccharomyces pombe
Atsumi, T.; Nishio, T.; Niwa, H.; Takeuchi, J.; Bando, H.; Shimizu, C.; Yoshioka, N.; Bucala, R.; Koike, T.
Expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase/PFKFB3 isoforms in adipocytes and their potential role in glycolytic regulation
Diabetes
54
3349-3357
2005
Homo sapiens, Mus musculus
Wu, C.; Okar, D.A.; Stoeckman, A.K.; Peng, L.J.; Herrera, A.H.; Herrera, J.E.; Towle, H.C.; Lange, A.J.
A potential role for fructose-2,6-bisphosphate in the stimulation of hepatic glucokinase gene expression
Endocrinology
145
650-658
2004
Mus musculus
Donthi, R.V.; Ye, G.; Wu, C.; McClain, D.A.; Lange, A.J.; Epstein, P.N.
Cardiac expression of kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase inhibits glycolysis, promotes hypertrophy, impairs myocyte function, and reduces insulin sensitivity
J. Biol. Chem.
279
48085-48090
2004
Mus musculus
Arden, C.; Hampson, L.J.; Huang, G.C.; Shaw, J.A.; Aldibbiat, A.; Holliman, G.; Manas, D.; Khan, S.; Lange, A.J.; Agius, L.
A role for PFK-2/FBPase-2 as distinct from fructose 2,6-bisphosphate in regulation of insulin secretion in pancreatic beta-cells
Biochem. J.
411
41-51
2007
Homo sapiens, Mus musculus, Mus musculus C57/BL6, Rattus norvegicus, Rattus norvegicus Wistar
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
Mus musculus (Q3U3S6), Mus musculus
Merrins, M.J.; Bertram, R.; Sherman, A.; Satin, L.S.
Phosphofructo-2-kinase/fructose-2,6-bisphosphatase modulates oscillations of pancreatic islet metabolism
PLoS ONE
7
e34036
2012
Mus musculus
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