Information on EC 2.7.11.20 - elongation factor 2 kinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.20
-
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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-
-
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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
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
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
-
-
-
-
?
ATP + cortactin
ADP + phosphorylated cortactin
show the reaction diagram
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i.e. SRC8, an Src substrate, phosphorylation peptide sequence is EYQGK-T-EKHAS
-
-
?
ATP + heat shock protein 60
ADP + phosphorylated heat shock protein 60
show the reaction diagram
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i.e. HSPD1, phosphorylation peptide sequence is TKDGV-T-VAKSI
-
-
?
ATP + hematological and neurological expressed 1-like protein
ADP + phosphorylated hematological and neurological expressed 1-like protein
show the reaction diagram
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i.e. HN1L, phosphorylation peptide sequence is FGSPV-T-ATSRL
-
-
?
ATP + heterogeneous nuclear ribonucleoprotein A1
ADP + phosphorylated heterogeneous nuclear ribonucleoprotein A1
show the reaction diagram
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i.e. HNRNPA1, phosphorylation peptide sequence is VSRED-S-QRPGA
-
-
?
ATP + immunoglobulin-binding protein 1
ADP + phosphorylated immunoglobulin-binding protein 1
show the reaction diagram
-
i.e. IGBP1, phosphorylation peptide sequence is EDDEQ-T-LHRAR
-
-
?
ATP + MH-1 peptide
ADP + phosphorylated MH-1 peptide
show the reaction diagram
ATP + microtubule-associated protein 4
ADP + phosphorylated microtubule-associated protein 4
show the reaction diagram
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i.e. MAP4, phosphorylation peptide sequence is TEAAA-T-TRKPE
-
-
?
ATP + N-myc downstream-regulated gene 1 protein
ADP + phosphorylated N-myc downstream-regulated gene 1 protein
show the reaction diagram
-
i.e. NDRG1, phosphorylation peptide sequence is TSLDG-T-RSRSH
-
-
?
ATP + PEST proteolytic signal-containing nuclear protein
ADP + phosphorylated PEST proteolytic signal-containing nuclear protein
show the reaction diagram
-
i.e. PCNP, phosphorylation peptide sequence is AIGSQ-T-TKKAS
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-
?
ATP + prothymosin alpha
ADP + phosphorylated prothymosin alpha
show the reaction diagram
-
i.e. PTMA, phosphorylation peptide sequence is TSSEI-T-TKDLK
-
-
?
ATP + RKKFGESEKTKTKEFL
ADP + ?
show the reaction diagram
-
-
-
-
?
ATP + SAP domain-containing ribonucleoprotein
ADP + phosphorylated SAP domain-containing ribonucleoprotein
show the reaction diagram
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i.e. SARNP, phosphorylation peptide sequence is GTTED-T-EAKKR
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-
?
ATP + scaffold attachment factor B2
ADP + phosphorylated scaffold attachment factor B2
show the reaction diagram
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i.e. SAFB2, phosphorylation peptide sequence is VISVK-T-TSRSK
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-
?
ATP + U4/U6 small nuclear ribonucleoprotein Prp31
ADP + phosphorylated U4/U6 small nuclear ribonucleoprotein Prp31
show the reaction diagram
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i.e. PRP31, phosphorylation peptide sequence is ERLGL-T-EIRKQ
-
-
?
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 + [eukaryotic translation initiation factor 2]
ADP + [eukaryotic translation initiation factor 2]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
-
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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-
?
ATP + [eukaryotic translation initiation factor 2]
ADP + [eukaryotic translation initiation factor 2]phosphate
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
calcium/calmodulin
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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
484954
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inhibits eEF2 phosphorylation in cells as well as in vitro
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7-amino-1-cyclopropyl-3-ethyl-1,2,3,4-tetrahydro-2,4-dioxo-pyrido[2,3-d]pyrimidine-6-carboxamide
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inhibits eEF2 phosphorylation in cells as well as in vitro
7-amino-1-cyclopropyl-3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-6-carboxamide
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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
EDTA
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ethanol
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decreases phosphorylation of eEF2K, whereas elongation factor 2 phosphorylation increases, but this response is not mediated by eEF2K
JAN-384
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a JAN-384 highly selective eEF2K inhibitor, comparison to inhibition of other protein kinases
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JAN-452
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slight inhibition
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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
serotonin
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inhibits the enzyme in synaptosomes and in isolated neurites, antagonizes rapamycin/5-hydroxytryptamine, mechanism
shRNA
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siRNA
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TS2
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1,3-selenazine derivative
TS4
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1,3-selenazine derivative
TX-1123
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additional information
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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
bicuculline
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elevation of eEF2K activity with bicuculline, a GABA receptor antagonist
calcium/calmodulin
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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
Homo sapiens
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pH 7.5, 30°C
0.000005
JAN-384
Mus musculus
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pH and temperature not specified in the publication
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0.03
JAN-452
Mus musculus
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pH and temperature not specified in the publication
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0.00006 - 0.0048
NH125
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
22
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assay at room temperature
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
81499
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x * 81499, calculation from nucleotide sequence
82000
-
x * 82000, light scattering analysis, calculated from sequence
90000
-
extracted from gastric epithelial cells, determined by SDS-PAGE and Western blot analysis
95000
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x * 95000, SDS-PAGE
100000
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recombinant protein, determined by SDS-PAGE
160000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
side-chain modification
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 0.1 M Bis-Tris (pH 5.5) and 21-28% (w/v) polyethylene glycol 2000
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
Ni-NTA column chromatography and Superdex 75 gel filtration
recombinant full-length human calmodulin (CaM), the predicted calmodulin-binding segment of human eEF-2K, residues 74-100 (eEF-2KCBD), and full-length eEF-2K
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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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recombinant GST-tagged wild-type and mutant eEF2K enzymes from Escherichia coli strain Rosetta(DE3)pLysS
recombinant His-tagged enzyme from Escherichia coli strain BL21 Rosetta 2 by nickel affinity chromatography, ultrafiltration, cleavage of the tag with Sumo protease, and anion exchange chromatography, followed by gel filtration
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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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expressed in Escherichia coli Rosetta (DE3) cells
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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recombinant coexpression of full-length human calmodulin (CaM), the predicted calmodulin-binding segment of human eEF-2K, residues 74-100 (eEF-2KCBD), and full-length eEF-2K
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recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Rosetta 2
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recombinant overexpression of FLAG-tagged enzyme from pcDNA3.1 vector in HEK-293 cells, recombinant expression of GST-tagged wild-type and mutant eEF2K enzymes in Escherichia coli strain Rosetta(DE3)pLysS
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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the expression of the mRNA for EEF2K is probably regulated in multiple ways, e.g. downstream of AMPK, and in some settings by mTORC1 signaling and HIF1
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
-
complete loss of activity
C318A
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complete loss of activity
D274A
-
loss of ability to bind ATP
D97A
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site-directed mutagenesis
H213A
-
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
P98A
-
site-directed mutagenesis
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
T482A
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catalytically inactive mutant
W85S
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site-directed mutagenesis, Mutation of residue W85 to S85 substantially weakens interactions between full-length eEF-2K and CaM in vitro and reduces eEF-2 phosphorylation in cells
W99A
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site-directed mutagenesis
W99L
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site-directed mutagenesis
D97A
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site-directed mutagenesis
P96A
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site-directed mutagenesis
W99A
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site-directed mutagenesis
W99L
-
site-directed mutagenesis
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