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Information on EC 2.7.1.11 - 6-phosphofructokinase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
The enzyme from rabbit muscle displays absolute stereoselectivity for the beta-anomer of D-fructofuranose 6-phosphate [9-11]. D-Tagatose 6-phosphate and sedoheptulose 7-phosphate can act as acceptors. UTP, CTP and ITP can act as donors. Not identical with EC 2.7.1.105 6-phosphofructo-2-kinase.
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
phosphofructokinase, 6-phosphofructokinase, 6-phosphofructo-1-kinase, pfk-1, phosphofructokinase-1, pfk-m, phosphofructokinase 1, atp-dependent phosphofructokinase, atp-pfk, pfk-l, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6-phosphofructo-1-kinase
-
-
6-phosphofructokinase, platelet type
-
-
-
-
6-phosphofructose 1-kinase
-
-
-
-
6-phosphofructose-1-kinase
-
-
-
-
ATP-dependent 6-phosphofructokinase
-
-
ATP-dependent PFK
-
ATP-dependent phosphofructokinase
-
-
-
-
ATP-PFK
-
-
-
-
ATP: D-fructose-6-phosphate-1-phosphotransferase
-
-
D-fructose-6-phosphate 1-phosphotransferase
-
-
-
-
fructose 6-phosphate kinase
-
-
-
-
fructose 6-phosphokinase
-
-
-
-
kinase, phosphofructo- (phosphorylating)
-
-
-
-
nucleotide triphosphate-dependent phosphofructokinase
-
-
-
-
PFK-L
PFK-M
PFK2
-
-
-
-
PFKP
phosphofructokinase 1 platelet isoform
phospho-1,6-fructokinase
-
-
-
-
phosphofructokinase
phosphofructokinase 1
-
-
-
-
phosphofructokinase-1
phosphofructokinase-P
-
phosphohexokinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:D-fructose-6-phosphate 1-phosphotransferase
The enzyme from rabbit muscle displays absolute stereoselectivity for the beta-anomer of D-fructofuranose 6-phosphate [9-11]. D-Tagatose 6-phosphate and sedoheptulose 7-phosphate can act as acceptors. UTP, CTP and ITP can act as donors. Not identical with EC 2.7.1.105 6-phosphofructo-2-kinase.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-80-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + D-fructose 1,6-bisphosphate
ATP + D-fructose 6-phosphate
show the reaction diagram
for human cells, the measured K0.5(ADP)0:5 values for the reaction with ADP and D-fructose 1,6-bisphosphate exceeds the cytosolic concentrations of ADP, but as steady-state concentrations of F0.5(D-fructose 1,6-bisphosphate) are lower than the K0.5(D-fructose 1,6-bisphosphate) values, it seems likely that under steady-state conditions the reverse reaction would indeed be inefficient. However, cells can be subjected to extreme conditions of stress and nutrient deprivation and the phosphofructokinase reverse flux may be very different in non-steady state, glucose-poor conditions and Q values of 500 or above can easily be achieved if ATP or glucose-6-phosphate are (transiently) depleted
-
-
r
ATP + D-fructose 1-phosphate
ADP + D-fructose 1,6-bisphosphate
show the reaction diagram
ATP + D-fructose 6-phosphate
ADP + D-fructose 1,6-bisphosphate
show the reaction diagram
additional information
?
-
-
insulin may increase the glucose consumption in human erythrocytes, through a mechanism involving Ca2+ influx, calmodulin and the detachment of 6-phosphofructose-1-kinase from the erythrocyte membrane
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + D-fructose 1-phosphate
ADP + D-fructose 1,6-bisphosphate
show the reaction diagram
-
key enzyme of glucose metabolism
-
-
?
ATP + D-fructose 6-phosphate
ADP + D-fructose 1,6-bisphosphate
show the reaction diagram
additional information
?
-
-
insulin may increase the glucose consumption in human erythrocytes, through a mechanism involving Ca2+ influx, calmodulin and the detachment of 6-phosphofructose-1-kinase from the erythrocyte membrane
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
-
Mn2+
-
activation
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
citrate
D-Fructose 1-phosphate
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
D-fructose 2,6-bisphosphate
-
-
D-Glucose 1,6-bisphosphate
-
0.02 mM, 474% and 360% activation of M- and L-type PFK, respectively
fructose 6-phosphate
S0.5 value for wild-type 0.88 mM, in presence of 1 mM AMP S0.5 value 0.052 mM. S0.5 value for N-terminal truncation mutant 0.089 mM, in presence of 1 mM AMP S0.5 value 0.030 mM
additional information
-
addition of oestradiol increases enzyme activity in intact cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0151 - 0.25
ATP
0.047 - 0.45
D-fructose 6-phosphate
additional information
ADP
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
357
ATP
-
wild type enzyme, at pH 7.0 in 50 mM HEPES, 100 mM KCl, 5 mM MgCl2 and 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.3 - 3.4
ADP
0.7 - 10
ATP
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
99.5
-
human skeletal muscle
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
phosphofructokinase-P is overexpressed in diverse types of cancer including HeLa cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug target
overexpression of phosphofructokinase-P by cancer cells is related to activation of survival pathways via upregulation ofMAPK and suggest PFK-P as a promising target for cancer therapy
malfunction
metabolism
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PFKAL_HUMAN
780
0
85018
Swiss-Prot
other Location (Reliability: 2)
PFKAM_HUMAN
780
0
85183
Swiss-Prot
other Location (Reliability: 2)
PFKAP_HUMAN
784
0
85596
Swiss-Prot
other Location (Reliability: 1)
A0A2R8Y891_HUMAN
883
0
96908
TrEMBL
other Location (Reliability: 4)
Q16184_HUMAN
19
0
2081
TrEMBL
other Location (Reliability: 2)
A0A7I2V3Z0_HUMAN
746
0
81800
TrEMBL
other Location (Reliability: 5)
A0A024R0Y5_HUMAN
780
0
85183
TrEMBL
other Location (Reliability: 2)
Q7KYX9_HUMAN
465
0
51065
TrEMBL
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
74250
-
x * 74250, L-type PFK
76000
-
x * 76000, SDS-PAGE
79500
-
x * 79500, M-type PFK
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oligomer
phosphofructokinase-1 assembles into filaments. Negative-stain electron micrographs reveals that filaments are apolar and made of stacked tetramers oriented with exposed catalytic sites positioned along the edge of the polymer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
insulin increases phosphorylation of human erythrocyte enzyme
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structures of the mammalian 6-phosphofructokinase PFK1 tetramer, for the human platelet isoform, in complex with MgATPMg2- and ADP at 3.1 and 3.4 A resolution, respectively. The structures reveal substantial conformational changes in the enzyme upon nucleotide hydrolysis as well as a unique tetramer interface. Mutations of residues in this interface can affect tetramer formation, enzyme catalysis and regulation. Somatic PFK1 mutations identified in human cancers have distinct effects on allosteric regulation of enzymic activity and lactate production
to 6.0 A resolution, space group P6222. Enzyme crystallizes as a dimer representing half of the physiologically active homotetramer
trunctation mutant in complex with ATP and with ADP, fructose 6-phosphate and fructose 1,6-bisphosphate, to 2.67-2.80 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D543A
-
the mutation causes an increased efficacy of ATP at the inhibitory allosteric binding site. The mutation drastically increases K0.5 for AMP. The activating effect of ADP found in wild type enzyme is completely lost
D564N
somatic mutation identified in human cancers. Mutant has decreased maximum velocity and affinity for fructose 6-phosphate
E657A
mutant has reduced affinity of about 4.5 mM for frucotse 6-phosphate, compared with about 0.8 mM in wild type, and an 2fold decrease in maximum activity
H242A
-
the mutant enzyme shows reduced Km value for ATP and 38.4% residual activity in the presence of 4.5 mM ADP
K386A
-
the mutant enzyme shows increased Km value for ATP and 33.1% residual activity in the presence of 4.5 mM ADP
K678A
-
the mutant enzyme shows reduced Km value for ATP. Ki values of ADP and ATP remain unchanged
N341A
N341A/R246A/K386A
-
the mutant enzyme shows reduced Km value for ATP and 21.9% residual activity in the presence of 4.5 mM ADP
N426S
somatic mutation identified in human cancers. Mutation partially relieves ATP inhibition
R246A
-
the mutant enzyme shows slightly increased Km value for ATP and 41.7% residual activity in the presence of 4.5 mM ADP
R246A/K386A
-
the mutant enzyme shows increased Km value for ATP and 33.2% residual activity in the presence of 4.5 mM ADP
R48C
somatic mutation identified in human cancers. Residue Arg48 interacts with a bound phosphate ion in the structure, and the mutant shows reduced citrate inhibition
S377A
-
the mutant enzyme shows reduced Km value for ATP. Ki values of ADP and ATP remain unchanged
S377A/K678A
-
the mutant enzyme shows reduced Km value for ATP. Ki values of ADP and ATP are significantly reduced in this mutant
additional information
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, purified enzyme with 10% glycerol (v/v), 2 weeks, no loss of activity
-
5°C, 50 mM potassium phosphate buffer, pH 8, 1 mM EDTA, 1 mM AMP, 1 mM dithiothreitol, 2 mM fructose 6-phosphate, 30% loss of activity per month
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
10% (w/v) PEG precipitation, DE52 column chromatography, Blue-Sepharose column chromatography, phosphocellulose column chromatography, and Superdex 200 gel filtration
-
batch DEAE-cellulose, ammonium sulfate, heat, DEAE-cellulose, Blue Dextran
-
Cibacron Blue F3GA-Sephadex G75 gel filtration, Resource Q column chromatography, and BioSep SEC-S4000 gel filtration
-
PEG 6000 precipitation, Resource Q column chromatography, and BioSep SEC-S4000 gel filtration
-
QAE-Sepharose, partially purified
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in pfk-deficient Saccharomyces cerevisiae strain HD152-1D
-
expressed in Saccharomyces cerevisiae strain HD114-8D
-
expression in Escherichia coli
expression in Saccharomyces cerevisiae
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
phosphofructokinase-P is overexpressed in diverse types of cancer including HeLa cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bloxham, D.P.; Lardy, H.A.
Phosphofructokinase
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
8
239-278
1973
Klebsiella aerogenes, Arthrobacter crystallopoietes, Glutamicibacter nicotianae, Bos taurus, Brassica oleracea var. gemmifera, Saccharomyces cerevisiae, Gallus gallus, Clostridium pasteurianum, Oryctolagus cuniculus, Daucus carota, Dictyostelium discoideum, Escherichia coli, Fasciola hepatica, Thermus thermophilus, Ovis aries, Homo sapiens, Lactiplantibacillus plantarum, Lacticaseibacillus casei, Mus musculus, Neurospora crassa, Pisum sativum, Rattus norvegicus, Zea mays
-
Manually annotated by BRENDA team
Massey, T.; Deal, W.C.
Phosphofructokinase from porcine liver and kidney and from other mammalian tissues
Methods Enzymol.
42C
99-110
1975
Bos taurus, Capra hircus, Gallus gallus, Oryctolagus cuniculus, Ovis aries, Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Layzer, R.B.
Phosphofructokinase from human erythrocytes
Methods Enzymol.
42C
110-115
1975
Homo sapiens
-
Manually annotated by BRENDA team
Durante, P.; Raleigh, X.; Gomez, M.E.; Campos, G.; Ryder, E.
Isozyme analysis of human normal polymorphonuclear leukocyte phosphofructokinase
Biochem. Biophys. Res. Commun.
216
898-905
1995
Homo sapiens
Manually annotated by BRENDA team
Xie, P.; Liu, M.L.; Gu, Y.P.; Lu, J.; Xu, X.; Zeng, W.M.; Song, H.P.
Oestrogen improves glucose metabolism and insulin signal transduction in HepG2 cells
Clin. Exp. Pharmacol. Physiol.
30
643-648
2003
Homo sapiens
Manually annotated by BRENDA team
Zancan, P.; Sola-Penna, M.
Calcium influx: a possible role for insulin modulation of intracellular distribution and activity of 6-phosphofructo-1-kinase in human erythrocytes
Mol. Genet. Metab.
86
392-400
2005
Homo sapiens
Manually annotated by BRENDA team
Zancan, P.; Sola-Penna, M.
Regulation of human erythrocyte metabolism by insulin: cellular distribution of 6-phosphofructo-1-kinase and its implication for red blood cell function
Mol. Genet. Metab.
86
401-411
2005
Homo sapiens
Manually annotated by BRENDA team
Brueser, A.; Kirchberger, J.; Schoeneberg, T.
Altered allosteric regulation of muscle 6-phosphofructokinase causes Tarui disease
Biochem. Biophys. Res. Commun.
427
133-137
2012
Oryctolagus cuniculus, Homo sapiens
Manually annotated by BRENDA team
Martinez-Costa, O.; Sanchez, V.; Lzaro, A.; Hernandez, E.; Tornheim, K.; Aragon, J.
Distinct functional roles of the two terminal halves of eukaryotic phosphofructokinase
Biochem. J.
445
213-218
2012
Dictyostelium discoideum, Homo sapiens
Manually annotated by BRENDA team
Brueser, A.; Kirchberger, J.; Kloos, M.; Straeter, N.; Schoeneberg, T.
Functional linkage of adenine nucleotide binding sites in mammalian muscle 6-phosphofructokinase
J. Biol. Chem.
287
17546-17553
2012
Homo sapiens
Manually annotated by BRENDA team
Kloos, M.; Brser, A.; Kirchberger, J.; Schneberg, T.; Strter, N.
Crystallization and preliminary crystallographic analysis of human muscle phosphofructokinase, the main regulator of glycolysis
Acta Crystallogr. Sect. F
70
578-582
2014
Homo sapiens (P08237), Homo sapiens
Manually annotated by BRENDA team
Kloos, M.; Brueser, A.; Kirchberger, J.; Schoeneberg, T.; Straeter, N.
Crystal structure of human platelet phosphofructokinase-1 locked in an activated conformation
Biochem. J.
469
421-432
2015
Homo sapiens (Q01813), Homo sapiens
Manually annotated by BRENDA team
Webb, B.A.; Forouhar, F.; Szu, F.E.; Seetharaman, J.; Tong, L.; Barber, D.L.
Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations
Nature
523
111-114
2015
Homo sapiens (Q01813), Homo sapiens
Manually annotated by BRENDA team
Wang, G.; Xu, Z.; Wang, C.; Yao, F.; Li, J.; Chen, C.; Sun, S.
Differential phosphofructokinase-1 isoenzyme patterns associated with glycolytic efficiency in human breast cancer and paracancer tissues
Oncol. Lett.
6
1701-1706
2013
Homo sapiens
Manually annotated by BRENDA team
Fernandes, P.; Kinkead, J.; McNae, I.; Bringaud, F.; Michels, P.; Walkinshaw, M.
The kinetic characteristics of human and trypanosomatid phosphofructokinases for the reverse reaction
Biochem. J.
476
179-191
2019
Leishmania infantum (A4I4W5), Trypanosoma brucei brucei (O15648), Homo sapiens (P08237), Homo sapiens (P17858), Homo sapiens (Q01813), Trypanosoma cruzi (Q4E657), Trypanosoma cruzi CL Brener (Q4E657)
Manually annotated by BRENDA team
Bhise, S.; Rao, J.; Hegde, M.; Katyare, S.
Type 2 diabetes differentially affects the substrate saturation kinetic attributes of erythrocyte hexokinase and phosphofructokinase
FEBS Lett.
594
240-250
2020
Homo sapiens (Q01813)
Manually annotated by BRENDA team
Lee, J.; Shao, F.; Ling, J.; Lu, S.; Liu, R.; Du, L.; Chung, J.; Koh, S.; Leem, S.; Shao, J.; Xing, D.; An, Z.; Lu, Z.
Phosphofructokinase 1 platelet isoform promotes beta-catenin transactivation for tumor development
Front. Oncol.
10
211
2020
Homo sapiens (Q01813), Homo sapiens
Manually annotated by BRENDA team
Webb, B.A.; Dosey, A.M.; Wittmann, T.; Kollman, J.M.; Barber, D.L.
The glycolytic enzyme phosphofructokinase-1 assembles into filaments
J. Cell Biol.
216
2305-2313
2017
Homo sapiens (P17858)
Manually annotated by BRENDA team
Cardim Pires, T.R.; Albanese, J.M.; Schwab, M.; Marette, A.; Carvalho, R.S.; Sola-Penna, M.; Zancan, P.
Phosphofructokinase-P modulates P44/42 MAPK levels in HeLa Cells
J. Cell. Biochem.
118
1216-1226
2017
Homo sapiens (Q01813)
Manually annotated by BRENDA team