Information on EC 2.7.1.105 - 6-phosphofructo-2-kinase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
2.7.1.105
-
RECOMMENDED NAME
GeneOntology No.
6-phosphofructo-2-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
fructose 2,6-bisphosphate biosynthesis
-
-
Fructose and mannose metabolism
-
-
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 hide
78689-77-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cv. Columbia
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Jerusalem artichoke
-
-
Manually annotated by BRENDA team
crayfish
-
-
Manually annotated by BRENDA team
frog
-
-
Manually annotated by BRENDA team
castor bean
-
-
Manually annotated by BRENDA team
potato plant, enzyme of Solanum tuberosum is 83% identical with enzyme of Zea mays and 72% identical with enzyme of Pinus taeda
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
PFKFB3 enzymes are activated in human cancers
metabolism
-
glycolytic enzyme is present as testis-specific isoforms, these isoforms are expressed specifically or predominantly in spermatogenic cells, often during the post-meiotic phase, and replace the ubiquitous isozymes that are also present in somatic cells
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + beta-D-fructose 2,6-bisphosphate
ATP + beta-D-fructose 6-phosphate
show the reaction diagram
-
reverse reaction, at 50% the rate of forward reaction
-
r
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
ATP + D-fructose 6-phosphate
ADP + D-fructose 2,6-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + D-psicose 6-phosphate
?
show the reaction diagram
-
-
-
-
?
ATP + D-tagatose 6-phosphate
?
show the reaction diagram
-
-
-
-
?
ATP + L-sorbose 6-phosphate
?
show the reaction diagram
-
-
-
-
?
CTP + D-fructose 6-phosphate
CDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
-
-
-
-
?
GTP + beta-D-fructose 6-phosphate
GDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
ITP + beta-D-fructose 6-phosphate
IDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
-
-
-
-
?
MgATP2- + beta-D-fructose 6-phosphate
?
show the reaction diagram
UTP + D-fructose 6-phosphate
UDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
GMP
-
activation
IMP
-
activation
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
AsO43-
phosphate
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,5-anhydro-D-mannitol 6-phosphate
-
-
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-phosphoglycerate
-
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
AICAR, associated with phosphorylation of PFK-2 on Ser-32, phosphorylation increased of both wild-type and overexpressed PFK-2 protein in hepatocytes
beta-D-fructose 2,6-bisphosphate
beta-D-fructose 6-phosphate
modeling of beta-D-fructose 6-phosphate as inhibitor
citrate
dihydroxyacetone phosphate
diphosphate
glucagon
glycerate 2-phosphate
Glycerol 2-phosphate
-
-
glycerol 3-phosphate
20% inhibition at 2mM
glycolate 2-phosphate
-
-
guanidine
-
inactivation, unfolding
m-periodate
-
strong, DTT protects or reverses
Mg2+
-
MgATP
MgATP
-
inhibited by, structure determination reveals substrate inhibition due to sequential binding of two MgATP molecules per subunit, the first at the usual site occupied by the nucleotide in homologous enzymes and the second at the allosteric site, making a number of direct and Mg-mediated interactions with the first, two configurations observed for the second MgATP, one of which involves interactions with Tyr-23 from the adjacent subunit in the dimer and the other making an unusual non-Watson-Crick base pairing with the adenine in the substrate ATP
MgATP2-
MgNTP
-
strain DF903, substrate inhibition, most effective: MgATP2, at low fructose concentration
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N-(1-pyrenil)maleimide
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complete loss of catalytic activity, but modified enzyme is able to bind beta-D-fructose 6-phosphate, the presence of MgATP2- completely protects the enzyme activity, the modified enzyme elutes as a monomer
N-Bromoacetylethanolamine
o-phthalaldehyde
-
kinetics, DTT or substrates do not protect
phosphate
-
inhibits wild-type and mutant enzym E190Q. E190 contributs to the mechanism of phosphate inhibition in Pfk-2. E190Q mutant presents alterations in the inhibition by MgATP2- and phosphate
phosphoenolpyruvate
protein kinase A
inactivation via a 7fold increase in Km for fructose 6-phosphate without alteration of Vmax
-
pyrene maleimide
-
incorporation of 2 mol per mol of enzyme subunit, modifiying Cys-238 and Cys-295, leads to rapid inactivation, MgATP2- protects Cys295, modification of Cys238 does not abolish activity
sn-glycerol 3-phosphate
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
glucose
-
inhibition by N-bromoacetylethanolamine
Insulin
-
activation of transfected heart enzyme in human embryonic kidney 293 cells by inducing the phosphorylation of Ser466 and Ser483, activation is mediated by 3-phosphoinositide-dependent kinase-1, protein kinase B is in vivo not essential, activation is sensitive to LY294002 and wortmannin and insensitive to rapaycin and PD98059
-
iodoacetamide
additional information
-
one enzyme form is activated dramatically as result of modification by MgATP during preincubation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00087 - 1.62
ATP
0.02 - 0.21
beta-D-fructose 2,6-bisphosphate
0.0038 - 39
beta-D-fructose 6-phosphate
0.9 - 2
CTP
0.0094 - 0.1
D-fructose 6-phosphate
7.4
D-psicose 6-phosphate
-
pH 7.5, 30C
15
D-tagatose 6-phosphate
-
pH 7.5, 30C
0.35 - 1.5
GTP
0.3
ITP
-
pH 8.2, 30C, strain DF903
0.175
L-Sorbose 6-phosphate
-
pH 7.5, 30C
0.0072 - 2
MgATP2-
0.78 - 2.3
UTP
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.14 - 0.19
ATP
0.17 - 9320
beta-D-fructose 6-phosphate
0.14 - 53
D-fructose 6-phosphate
1.43 - 9320
MgATP2-
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.095
2,5-anhydro-D-mannitol 6-phosphate
-
pH 7.5, 30C
0.025
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
-
inhibition of recombinant PFKFB3 protein, no inhibition of purified PFK-1 activity
0.16
ADP
-
pH 6.6, 25C
0.008 - 0.01
ATP
8.5 - 13.4
beta-D-fructose 6-phosphate
0.025 - 6
citrate
0.25 - 1.9
dihydroxyacetone phosphate
0.026 - 0.16
diphosphate
0.016 - 0.45
glycerate 2-phosphate
0.084
Glycerate 3-phosphate
pH 7.8, 25C
0.02 - 0.18
glycolate 2-phosphate
2 - 15
N-Bromoacetylethanolamine
0.028
o-phthalaldehyde
-
pH 7.4, room temperature
0.014 - 2.3
phosphoenolpyruvate
0.018 - 8.07
sn-glycerol 3-phosphate
additional information
additional information
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00031
-
skeletal muscle
0.00295
-
heart
0.0104 - 0.0159
-
0.011
purified enzyme
0.021
-
liver
0.04
-
-
0.042
-
-
0.055
-
adult
0.068
-
-
0.075
-
-
0.08
-
foetal
0.092
-
-
0.11
-
-
0.142
-
-
0.2
recombinant purified HBP1 from Escherichia coli
0.277
-
specific PFK-2 activity of the recombinant PFKFB3 protein determined by measurement of fructose 2,6-bisphosphate
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
assay at
7.3 - 8.4
-
wild-type enzyme
7.4 - 7.9
-
-
7.5
-
assay at
7.5 - 8
-
native enzyme
8.4
-
5 mM phosphate
9.3
-
muscle-type isozyme
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8.5
-
continuous increase of activity from pH 5.5 with 70% of maximal activity to maximal activity from pH 7.5 to 8.5, phosphorylated enzyme
6 - 10
6.6 - 8.5
-
about half-maximal activity at pH 6.6 and about 90% of maximal activity at pH 8.5, native enzyme
7 - 8.2
7.1 - 8.3
-
about half-maximal activity at pH 7.1 and 8.3, peak 1 enzyme
7.3 - 9.5
-
about half-maximal activity at pH 7.3 and 9.5
7.5 - 10
-
linear increase up to pH 10 from 10% of maximal activity at pH 7.5
7.8 - 8
-
MgATP-activated enzyme form
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.7 - 4.8
-
isoelectric focusing
9.3
isozymes, sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
equal amounts of isozyme L and M
Manually annotated by BRENDA team
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; low and high malignancy grades according to histological criteria, expression analysis in; low and high malignancy grades according to histological criteria, expression analysis in
Manually annotated by BRENDA team
-
ras-transformed
Manually annotated by BRENDA team
expression less detectable in; expression less detectable in
Manually annotated by BRENDA team
expression analysis in; expression analysis in; expression analysis in; expression analysis in
Manually annotated by BRENDA team
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resembles muscle enzyme
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
-
engineered to overexpress PFKFB3, inhibitor studies on recombinant PFKFB3 activity in
Manually annotated by BRENDA team
-
placenta-type isozyme is expressed in Kupffer cells of the liver
Manually annotated by BRENDA team
-
ras-transformed
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
expressed at high abundance in both hypothalami and clonal hypothalamic neurons
Manually annotated by BRENDA team
low expression; low expression
Manually annotated by BRENDA team
low expression in; low expression in
Manually annotated by BRENDA team
-
uPFK-2, tPFK-2
Manually annotated by BRENDA team
additional information