Information on EC 2.7.11.20 - elongation factor 2 kinase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
2.7.11.20
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RECOMMENDED NAME
GeneOntology No.
elongation factor 2 kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + [elongation factor 2] = ADP + [elongation factor 2] phosphate
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
SYSTEMATIC NAME
IUBMB Comments
ATP:[elongation factor 2] phosphotransferase
Requires Ca2+ and calmodulin for activity. The enzyme can also be phosphorylated by the catalytic subunit of EC 2.7.11.11, cAMP-dependent protein kinase. Elongation factor 2 is phosphorylated in several cell types in response to various growth factors, hormones and other stimuli that raise intracellular Ca2+ [1,2].
CAS REGISTRY NUMBER
COMMENTARY hide
116283-83-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Mus musculus C57BL/6J
C57BL/6J mice
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-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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
ATP + a protein
ADP + a phosphoprotein
show the reaction diagram
ATP + acetyl-RKKYKFNEDTERRRFL-amide
ADP + acetyl-RKKYKFNED(phospho)TERRRFL-amide
show the reaction diagram
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-
-
-
?
ATP + RKKFGESEKTKTKEFL
ADP + ?
show the reaction diagram
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-
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2] phosphate
show the reaction diagram
ATP + [elongation factor 2]
ADP + [elongation factor 2]phosphate
show the reaction diagram
ATP + [elongation factor 3]
ADP + [elongation factor 3]phosphate
show the reaction diagram
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-
-
-
?
ATP + [elongation translation factor 2]
ADP + [elongation translation factor 2]phosphate
show the reaction diagram
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-
-
-
?
ATP + [eukaryotic translation elongation factor 2]
ADP + [eukaryotic translation elongation factor 2] phosphate
show the reaction diagram
ATP + [eukaryotic translation initiation factor 2alpha]
ADP + [eukaryotic translation initiation factor 2alpha]phosphate
show the reaction diagram
ATP + [MHCK A peptide substrate]
ADP + [MHCK A peptide substrate] phosphate
show the reaction diagram
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i.e. YAYDTRYRR
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-
?
additional information
?
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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 + [elongation factor 2]
ADP + [elongation factor 2] phosphate
show the reaction diagram
ATP + [elongation factor 2]
ADP + [elongation factor 2]phosphate
show the reaction diagram
ATP + [elongation factor 3]
ADP + [elongation factor 3]phosphate
show the reaction diagram
-
-
-
-
?
ATP + [elongation translation factor 2]
ADP + [elongation translation factor 2]phosphate
show the reaction diagram
-
-
-
-
?
ATP + [eukaryotic translation elongation factor 2]
ADP + [eukaryotic translation elongation factor 2] phosphate
show the reaction diagram
ATP + [eukaryotic translation initiation factor 2alpha]
ADP + [eukaryotic translation initiation factor 2alpha]phosphate
show the reaction diagram
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GCN2 mediates translational control of gene expressionin amino acid-starved cells by phosphorylation of the eukaryotic translation initiation factor 2alpha associated to polyribosome and the regulatory GCN1-GCN20 complex, overview
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-
?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
calcium/calmodulin
dependent on
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-benzyl-3-cetyl-2-methylimidazolium iodide
2-((3,5-di-tert-butyl-4-hydroxyphenyl)-methylene)-4-cyclopentene-1,3-dione
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TX-1123
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bombesin
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a secretagogue, increases elongation rates, and decreases elongation factor 2 phosphorylation
Carbachol
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a secretagogue, increases elongation rates, and decreases elongation factor 2 phosphorylation
Cholecystokinin
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a secretagogue, increases elongation rates, increases phosphorylation of eEF2 kinase, and decreases elongation factor 2 phosphorylation reversed by rapamycin, PD98059, calyculin, or SB202190
compound C
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AMPK inhibitor compound C blocks eEF2K and eEF2 phosphorylation
ethanol
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decreases phosphorylation of eEF2K, whereas elongation factor 2 phosphorylation increases, but this response is not mediated by eEF2K
lopinavir
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i.e. LPV, increases the phosphorylation of eEF2 kinase on Ser366 reducing its activity, LPV affects eEF2 activity via an AMPK-eEF2K dependent pathway, overview
NH125
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an imidazolium histidine kinase inhibitor also inhibits the eukaryotic eEF-2 kinase enzyme in vitro and in vivo, IC50 is 60 nM, decreases viability of cancer cell lines with IC50S of 0.0007 to 0.0048 mM, overview
phorbol ester PMA
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rottlerin
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blocks the effects of stimulators AICAR and FBS
serotonin
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inhibits the enzyme in synaptosomes and in isolated neurites, antagonizes rapamycin/5-hydroxytryptamine, mechanism
TS2
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1,3-selenazine derivative
TS4
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1,3-selenazine derivative
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-deoxy-D-glucose
5-amino-4-imidazolecarboxyamide riboside
AICAR
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increases the levels of eEF2K phosphorylation more than 2fold
calcium/calmodulin
dependent on
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Calmodulin
calyculin
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reverses activation of the elongation factor 2 by dephosphorylation through cholecystokinin
carbonyl cyanide 3-chlorophenylhydrazone
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D-glucose
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high glucose or high insulin rapidly increase inactivating Ser366 phosphorylation of eEF2 kinase
FBS protein
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increases the levels of eEF2K phosphorylation more than 2fold
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GCN1-GCN20
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positive effectors, uncharged tRNAs activate GCN2 requiring direct interaction with both the GCN1-GCN20 regulatory complex and ribosomes
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Insulin
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high glucose or high insulin rapidly increase inactivating Ser366 phosphorylation of eEF2 kinase
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MG132
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addition to normoxic MCF10A cells results in a 5- to 10fold increase in eEF2K levels but has no effect on hypoxic MCF10A or HTB20 cells
mTOR
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mediates the insulin-induced activation of Ser78 phosphorylation, insulin-dependent decrease of eEF2 phosphorylation is blocked by rapamycin
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PD98059
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reverses activation of the elongation factor 2 by dephosphorylation through cholecystokinin
phosphorylated MEK
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activates the enzyme
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phosphorylated p70S6K
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activates the enzyme
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Rapamycin
rapamycin/5-hydroxytryptamine
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rapamycin activates the enzyme in neuron and antagonizes serotonin mediated by 5-hydroxytryptamine, rapamycin alone has no effect, but increases with 5-hydroxytryptamine the dephosphorylation of the eukaryotic elongation factor 2, 5-hydroxytryptamine decreases the phosphorylation of the eukaryotic elongation factor 2 at Thr57 in a rapamycin-sensitive manner, mechanism
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SB202190
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reverses activation of the elongation factor 2 by dephosphorylation through cholecystokinin
uncharged tRNAs
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activate GCN2 requiring direct interaction with both the GCN1-GCN20 regulatory complex and ribosomes
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additional information
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00006
1-benzyl-3-cetyl-2-methylimidazolium iodide
0.0007 - 0.0048
NH125
Homo sapiens
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decreases viability of cancer cell lines with IC50S of 0.0007 to 0.0048 mM, overview
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.536
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30°C, pH 7.5
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 7.2
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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glioblastoma cell line
Manually annotated by BRENDA team
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ovarian carcinoma cell line
Manually annotated by BRENDA team
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phosphorylated or dephosphorylated enzyme
Manually annotated by BRENDA team
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T98G and LN-229
Manually annotated by BRENDA team
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gastric epithelial cell
Manually annotated by BRENDA team
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oral epidermoid carcinoma cell line
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
primary mouse embryonic fibroblasts
Manually annotated by BRENDA team
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ovarian carcinoma cell line
Manually annotated by BRENDA team
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prostate carcinoma cell line
Manually annotated by BRENDA team
the enzyme is differentially regulated in separate compartments
Manually annotated by BRENDA team
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cell lines of head and neck cancer
Manually annotated by BRENDA team
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at the level of elongation
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
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glioblastoma cell line
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
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cancer cell line
Manually annotated by BRENDA team
additional information
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the enzyme expression and activity is increased in several forms of malignancy
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
90000
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extracted from gastric epithelial cells, determined by SDS-PAGE and Western blot analysis
100000
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recombinant protein, determined by SDS-PAGE
160000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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recombinant GST-tagged enzyme peptide mapping
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
in vivo half-life of the enzyme is 6 h, proteasome inhibitor MG132 prolonged the half-life of the enzyme to more than 24 h
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged enzyme from Escherichia coli strain BL21(DE3) by affinity chromatography
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recombinant GST-tagged wild-type and FLAG-tagged mutant enzymes from Escherichia coli
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with a nickel column by affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme expression as GST-tagged protein in Escherichia coli strain BL21(DE3)
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expression as a GST (glutathione transferase)-fusion protein in Escherichia coli
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expression in Escherichia coli
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expression in HEK-293 cells
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expression of GST-tagged enzyme in Escherichia coli
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expression of GST-tagged wild-type enzyme and of a FLAG-tagged mutant enzyme in Escherichia coli
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overexpression in transgenic wheat results in significant decreases in total free amino acid concentration in the grain, with free asparagine concentration in particular being much lower than in controls
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overexpression of the enzyme in glioma T98-G cells causes a 10fold increased resistance to inhibitor NH125
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using an EasyXpress Linear Template kit
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
over-expressed by a stressful, heat-stressed, environment, Helicobacter pylori infection enhances the EF-2K expression in HGC-27 cells as much as heat stress do
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S454A
neurons injected with mutant enzyme S454A shows significantly more phosphorylation of elongation factor 2 than do neurons injected with wild-type enzyme
C314A
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complete loss of activity
C318A
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complete loss of activity
D274A
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loss of ability to bind ATP
H213A
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complete loss of activity
H260A
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complete loss of activity
K170M
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complete loss of activity, loss of ability to bind ATP
K170R
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complete loss of activity, loss of ability to bind ATP
S366A
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activity with RKKFGESEKTKTKEFL is decreased approximately 90% compared to wild-type activity after preincubation for 60 min with MgATP2-
S445A
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate
S445D
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate
S474A
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate
S474D
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate
S500A
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate
S500D
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate. The mutation renders the enzyme Ca2+-independent
S78A/S366A
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phosphorylation-defective mutant, mutation results in an increased stability under normal culture conditions, t1/2 is above 24 h
T348E
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the mutant enzyme phosphorylates purified elongation factor 2 poorly compared with wild-type
T353A
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate
T353D
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no difference in activity compared to wild-type enzyme with respect to the ability to phosphorylate a peptide substrate
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
agriculture
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manipulation of TaGCN2 gene expression can be used to reduce free asparagine accumulation in wheat grain and the risk of acrylamide formation in wheat products
medicine
pharmacology
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the enzyme is a target for development of anticancer drugs
additional information