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Information on EC 2.7.11.20 - elongation factor 2 kinase and Organism(s) Rattus norvegicus and UniProt Accession P70531
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2.7.11.20 elongation factor 2 kinaseIUBMB Comments
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].
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Word Map
- 2.7.11.20
- rapamycin
-
perk
- starvation
- mtor
- synaptic
-
heme-regulated
- autophosphorylation
-
uncharged
- eif4e
-
pkr-like
-
ido
-
autokinase
-
alpha-kinase
-
acid-starved
-
cam-dependent
- rottlerin
- medicine
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histidyl-trna
- pharmacology
- agriculture
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
eef2k, eef-2k, eif2alpha kinase, eef-2 kinase, eef2 kinase, eukaryotic elongation factor 2 kinase, gcn2 kinase, eukaryotic elongation factor-2 kinase, elongation factor-2 kinase, elongation factor 2 kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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
116283-83-1
-
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
ATP + [elongation factor 2]
ADP + [elongation factor 2] phosphate
-
-
-
?
ATP + [eukaryotic elongation factor 2]
ADP + [eukaryotic elongation factor 2] phosphate
-
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2] phosphate
-
-
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2]phosphate
-
-
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2]phosphate
-
elongation factor 2 regulates the translation elongation through mTOR, p38, and MEK pathways, and is modulated through protein phosphatase 2A, overview
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2]phosphate
-
phosphorylation at Thr56
-
-
?
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
ATP + [elongation factor 2]
ADP + [elongation factor 2] phosphate
-
-
-
?
ATP + [eukaryotic elongation factor 2]
ADP + [eukaryotic elongation factor 2] phosphate
-
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2] phosphate
-
-
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2]phosphate
-
-
-
-
?
ATP + [elongation factor 2]
ADP + [elongation factor 2]phosphate
-
elongation factor 2 regulates the translation elongation through mTOR, p38, and MEK pathways, and is modulated through protein phosphatase 2A, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-benzyl-3-cetyl-2-methylimidazolium iodide
i.e. NH125, inhibits eEF2K activity via inhibition of alpha-kinase, a catalytic domain of eEF2K. In mesenteric artery from spontaneously hypertensive rats, the acetylcholine-induced endothelium-dependent relaxation is significantly impaired after long-term treatment with the inhibitor
7-amino-1-cyclopropyl-3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-6-carboxamide
i.e. A-484954, a pyrido-pyrimidinedione derivative that inhibits eEF2K in an ATP-competitive but CaM-independent manner
2-((3,5-di-tert-butyl-4-hydroxyphenyl)-methylene)-4-cyclopentene-1,3-dione
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TX-1123
bombesin
-
a secretagogue, increases elongation rates, and decreases elongation factor 2 phosphorylation
Carbachol
-
a secretagogue, increases elongation rates, and decreases elongation factor 2 phosphorylation
Cholecystokinin
-
a secretagogue, increases elongation rates, increases phosphorylation of eEF2 kinase, and decreases elongation factor 2 phosphorylation reversed by rapamycin, PD98059, calyculin, or SB202190
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
calyculin
-
reverses activation of the elongation factor 2 by dephosphorylation through cholecystokinin
PD98059
-
reverses activation of the elongation factor 2 by dephosphorylation through cholecystokinin
SB202190
-
reverses activation of the elongation factor 2 by dephosphorylation through cholecystokinin
Calmodulin
a central mediator of Ca2+-dependent signaling, the enzyme is dependent on calmodulin
Rapamycin
-
reverses activation of the elongation factor 2 by dephosphorylation through cholecystokinin
additional information
-
ATP depletion activates the enzyme in cardiomyocytes
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
activity of eEF2K is selectively increased in proliferating cells
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
enzyme silencing with eEF2K siRNA inhibits phosphorylation of JNK and NF-kappaB p65 as well as reactive oxygen species (ROS) production by TNF-alpha. In vascular smooth muscle cells, eEF2K siRNA also inhibits VCAM-1 induction and phosphorylation of JNK and NF-kappaB by TNF-alpha. In vascular endothelial cells, siRNA against eEF2K inhibited induction of VCAM-1 and endothelial-selectin as well as monocyte adhesion by TNF-alpha. Phenotypes, overview
malfunction
enzyme gene knockdown significantly augments glucose deprivation-induced cleavage of caspase-3 and apoptotic nuclear condensation. In contrast, enzyme gene knockdown significantly inhibits glucose deprivation-induced increase of microtubule-associated protein 1 light chain 3-II to -I ratio and autophagosome formation. Enzyme gene knockdown significantly inhibits GD-induced phosphorylation of adenosine monophosphate-activated protein kinase alpha and its downstream substrate, unc-51 like autophagy activating kinase 1
physiological function
eukaryotic elongation factor 2 kinase (eEF2K) prevents binding of eEF to the ribosome via phosphorylation of eEF and thus prevents further translation. The enzyme regulates the development of hypertension through oxidative stress-dependent vascular inflammation. eEF2K protein increases in mesenteric artery from spontaneously hypertensive rats. Enzyme eEF2K mediates TNF-alpha-induced vascular inflammation via reactive oxygen species-dependent mechanism, which is at least partly responsible for the development of hypertension in spontaneously hypertensive rats
physiological function
cardiac hypertrophy may be regulated at least partly via enzyme-eukaryotic elongation factor 2 signaling pathway
physiological function
the enzyme mediates the inhibition of cardiomyocyte death under glucose deprivation condition
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). EF2K_RAT
724
0
81489
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
additional information
-
the enzyme is ubiquitinated in vivo, ubiquitination and turnover is increased by inhibition of heat shock protein 90, enzyme degradation involves the proteasome
phosphoprotein
-
phosphorylation at Ser366 inhibits the enzyme, mediated by cholecystokinin
phosphoprotein
-
the enzyme performs autophosphorylation, stimulation of AMP-activated protein kinase, EC 2.7.11.11, by AMP leads to activation of the enzyme and to its phosphorylation at Ser398 in the regulatory domain, other phosphorylation sites of the enzyme are Ser78, Ser359, Ser377, and Ser366
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
generation of enzyme knoockout mice, silencing of the enzyme by siRNA expression
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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ryazanov, A.G.; Ward, M.D.; Mendola, C.E.; Pavur, K.S.; Dorovkov, M.V.; Wiedmann, M.; Erdjument-Bromage, H.; Tempst, P.; Parmer, T.G.; Prostko, C.R.; Germino, F.J.; Hait, W.N.
Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase
Proc. Natl. Acad. Sci. USA
94
4884-4889
1997
Caenorhabditis elegans (O01991), Caenorhabditis elegans, Homo sapiens (O00418), Homo sapiens, Mus musculus (O08796), Mus musculus, Rattus norvegicus (P70531)
Redpath, N.T.; Price, N.T.; Proud, C.G.
Cloning and expression of cDNA encoding protein synthesis elongation factor-2 kinase
J. Biol. Chem.
271
17547-17554
1996
Rattus norvegicus (P70531)
Sans, M.D.; Xie, Q.; Williams, J.A.
Regulation of translation elongation and phosphorylation of eEF2 in rat pancreatic acini
Biochem. Biophys. Res. Commun.
319
144-151
2004
Rattus norvegicus
Arora, S.; Yang, J.M.; Hait, W.N.
Identification of the ubiquitin-proteasome pathway in the regulation of the stability of eukaryotic elongation factor-2 kinase
Cancer Res.
65
3806-3810
2005
Homo sapiens, Rattus norvegicus
Browne, G.J.; Finn, S.G.; Proud, C.G.
Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398
J. Biol. Chem.
279
12220-12231
2004
Homo sapiens, Rattus norvegicus
Rose, A.J.; Alsted, T.J.; Jensen, T.E.; Kobber?, J.B.; Maarbjerg, S.J.; Jensen, J.; Richter, E.A.
A Ca(2+)-calmodulin-eEF2K-eEF2 signalling cascade, but not AMPK, contributes to the suppression of skeletal muscle protein synthesis during contractions
J. Physiol.
587
1547-1563
2009
Rattus norvegicus
Usui, T.; Okada, M.; Hara, Y.; Yamawaki, H.
Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation
Am. J. Physiol. Heart Circ. Physiol.
305
H756-H768
2013
Homo sapiens (O00418), Rattus norvegicus (P70531), Rattus norvegicus Wistar (P70531)
Kameshima, S.; Okada, M.; Yamawaki, H.
Eukaryotic elongation factor 2 (eEF2) kinase/eEF2 plays protective roles against glucose deprivation-induced cell death in H9c2 cardiomyoblasts
Apoptosis
24
359-368
2019
Rattus norvegicus (P70531)
Kameshima, S.; Okada, M.; Ikeda, S.; Watanabe, Y.; Yamawaki, H.
Coordination of changes in expression and phosphorylation of eukaryotic elongation factor 2 (eEF2) and eEF2 kinase in hypertrophied cardiomyocytes
Biochem. Biophys. Rep.
7
218-224
2016
Mus musculus (O08796), Rattus norvegicus (P70531)
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