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Information on EC 2.7.1.147 - ADP-specific glucose/glucosamine kinase and Organism(s) Homo sapiens and UniProt Accession Q9BRR6
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2.7.1.147 ADP-specific glucose/glucosamine kinaseIUBMB Comments
Requires Mg2+. The enzyme, characterized from a number of hyperthermophilic archaeal species, is highly specific for ADP. No activity is detected when ADP is replaced by ATP, GDP, phosphoenolpyruvate, diphosphate or polyphosphate.
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Word Map
- 2.7.1.147
-
hyperthermophilic
- thermococcus
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embden-meyerhof
- litoralis
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phosphofructokinases
- jannaschii
- furiosus
- glucokinases
- ribokinase
- methanococcales
- thermococcales
- 6-phosphofructokinase
- hexokinases
- atp-pfks
- methanosarcinales
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
Synonyms
adpgk, adp-dependent glucokinase, adp-pfk, adp-dependent kinase, tk1110, adp-gk, phpfk, adp-dependent hexokinase, adp-hk, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADP-dependent glucokinase
ADP-specific glucokinase
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-
-
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ADP:D-glucose 6-phosphotransferase
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-
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ADP-dependent glucokinase
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho-group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -
SYSTEMATIC NAME
IUBMB Comments
ADP:D-glucose/D-glucosamine 6-phosphotransferase
Requires Mg2+. The enzyme, characterized from a number of hyperthermophilic archaeal species, is highly specific for ADP. No activity is detected when ADP is replaced by ATP, GDP, phosphoenolpyruvate, diphosphate or polyphosphate.
CAS REGISTRY NUMBER
COMMENTARY
173585-07-4
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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
ADP + D-glucose
AMP + D-glucose 6-phosphate
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enzyme shows substrate inhibition at high glucose concentrations
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-
?
additional information
?
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poor activity with CDP. No substrates: ATP, 2-deoxyglucose, L-glucose, methyl-beta-D-xylopyranoside, D-glucosamine, L-rhamnose, D-tagatose, 3-O-methyl-D-glucopyranoside, 1-O-methyl-beta-D-glucopyranoside, 1-O-methyl-alpha-D-glucopyranoside, D-arabinose, L-arabinose, myo-inositol, D-ribose, D-xylose, D-galactose, D-fructose, D-mannose, D-fructose-6-phosphate, and alpha-D-glucose-1-phosphate
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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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8-bromoadenosine phosphate
competitive. The binding of the inhibitor induces major conformational changes
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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T cell activation-induces upregulation in ADPGK activity
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
metabolism
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human ADPGK catalyses ADP-dependent phosphorylation of glucose in vitro
physiological function
malfunction
ADPGK knock-out Ramos BL cells display abated in vitro and in vivo tumour aggressiveness, via tumour-macrophage co-culture, migration and Zebrafish xenograft studies. Perturbed glycolysis and visibly reduced markers of Warburg effect in ADPGK knock-out cells, finally leading to apoptosis. Knock-out cells show repression of MYC proto-oncogene, and up to four-fold reduction in accumulated mutations in translocated MYC
malfunction
upon activation, ADPGK knockout Jurkat T cells display increased cell death and ER stress. The increase in cell death results from a metabolic catastrophe and knockout cells displayed severely disturbed energy metabolism hindering induction of Warburg phenotype
physiological function
the enzyme plays a critical role in T cell receptor activation-induced remodeling of energy metabolism. The enzyme is part of a glucose sensing system in the ER modulating metabolism via regulation of N- and O-glycosylation
physiological function
the enzyme plays a major role in T-cell activation and induction of Warburg effect
malfunction
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down-regulation of ADPGK or GPD2 abundance inhibits oxidative signal generation and induction of NF-kappaB-dependent gene expression, whereas over-expression of ADPGK potentiates them
malfunction
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overexpression or suppression of ADPGK does not show any relevant effect
physiological function
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T cell activation-induced mitochondrial ROS production and NF-kappaB-driven gene expression depend on activation of ADPGK. ADPGK activation is accompanied by a rapid glucose uptake, downregulation of mitochondrial oxygen consumption, and deviation of glycolysis toward the glycerol-3-phosphate dehydrogenase shuttle
physiological function
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knockout of inc finger nucleases in each H-460 and HCT-11 cells lead to frameshift mutations in all alleles at the target site in exon 1 of ADP-dependent glucokinase ADPGK, and are ADPGK-null by immunoblotting. ADPGK knockout has little or noeffect on cell proliferation, but compromises the ability of H-460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions and anoxia. No such changes are found when ADPGK is knocked out in HCT-116 cells. Knockout of ADPGK in HCT-116 cells causes few changes in global gene expression, while knockout of ADPGK in H-460 cells causes notable up-regulation of mRNAs encoding cell adhesion proteins. No consistent effect on glycolysis under oxic conditions in a variety of media is observed. Oxygen consumption rates are generally lower in the ADPGK knockouts
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). ADPGK_HUMAN
497
0
54089
Swiss-Prot
Secretory Pathway (Reliability: 1)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method at 20°C, complex of the enzyme with glucose and 8-bromoadenosine phosphate
structures reveal a ribokinase-like tertiary fold similar to archaeal orthologues but with significant differences in some secondary structural elements. Both the unliganded and the AMP-bound ADPGK structures are in the open conformation and reveal the presence of a disulfide bond between conserved cysteines that is positioned at the nucleotide-binding loop. The AMP-bound structure defines the nucleotide-binding site with one of the disulfide bond cysteines coordinating the AMP with its main chain atoms
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H264A
greatly reduced activity, no substrate inhibition with glucose concentrations of up to 55 mM
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kaminski, M.M.; Sauer, S.W.; Kaminski, M.; Opp, S.; Ruppert, T.; Grigaravinius, P.; Grudnik, P.; Groene, H.J.; Krammer, P.H.; Guelow, K.
T cell activation is driven by an ADP-dependent glucokinase linking enhanced glycolysis with mitochondrial reactive oxygen species generation
Cell Rep.
2
1300-1315
2012
Homo sapiens
Richter, S.; Richter, J.P.; Mehta, S.Y.; Gribble, A.M.; Sutherland-Smith, A.J.; Stowell, K.M.; Print, C.G.; Ronimus, R.S.; Wilson, W.R.
Expression and role in glycolysis of human ADP-dependent glucokinase
Mol. Cell. Biochem.
364
131-145
2012
Homo sapiens
Richter, J.P.; Goroncy, A.K.; Ronimus, R.S.; Sutherland-Smith, A.J.
The Structural and functional characterization of mammalian ADP-dependent glucokinase
J. Biol. Chem.
291
3694-3704
2016
Homo sapiens (Q9BRR6)
Richter, S.; Morrison, S.; Connor, T.; Su, J.; Print, C.G.; Ronimus, R.S.; McGee, S.L.; Wilson, W.R.
Zinc finger nuclease mediated knockout of ADP-dependent glucokinase in cancer cell lines: effects on cell survival and mitochondrial oxidative metabolism
PLoS ONE
8
e65267
2013
Homo sapiens
Grudnik, P.; Kaminski, M.M.; Rembacz, K.P.; Kuska, K.; Madej, M.; Potempa, J.; Dawidowski, M.; Dubin, G.
Structural basis for ADP-dependent glucokinase inhibition by 8-bromo-substituted adenosine nucleotide
J. Biol. Chem.
293
11088-11099
2018
Homo sapiens (Q9BRR6), Homo sapiens, Pyrococcus horikoshii (O58328), Pyrococcus horikoshii ATCC 700860 (O58328)
Tandon, A.; Birkenhagen, J.; Nagalla, D.; Koelker, S.; Sauer, S.W.
ADP-dependent glucokinase as a novel onco-target for haematological malignancies
Sci. Rep.
10
13584
2020
Homo sapiens (Q9BRR6)
Imle, R.; Wang, B.T.; Stuetzenberger, N.; Birkenhagen, J.; Tandon, A.; Carl, M.; Himmelreich, N.; Thiel, C.; Groene, H.J.; Poschet, G.; Voelkers, M.; Guelow, K.; Schroeder, A.; Carillo, S.; Mittermayr, S.; Bones, J.; Kaminski, M.M.; Koelker, S.; Sauer, S.W.
ADP-dependent glucokinase regulates energy metabolism via ER-localized glucose sensing
Sci. Rep.
9
14248
2019
Danio rerio, Homo sapiens (Q9BRR6)
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Release 2023.1 (January 2023)
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