Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Eukaryotic elongation factor 2 kinase

Gene

Eef2k

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced (By similarity).By similarity

Catalytic activityi

ATP + [elongation factor 2] = ADP + [elongation factor 2] phosphate.

Enzyme regulationi

Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi295 – 3017ATPBy similarity

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calcium ion binding Source: InterPro
  • calmodulin binding Source: UniProtKB
  • elongation factor-2 kinase activity Source: RGD

GO - Biological processi

  • cellular response to anoxia Source: RGD
  • cellular response to brain-derived neurotrophic factor stimulus Source: RGD
  • cellular response to calcium ion Source: RGD
  • cellular response to cAMP Source: RGD
  • cellular response to insulin stimulus Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • positive regulation of dendritic spine morphogenesis Source: RGD
  • positive regulation of endocytosis Source: RGD
  • positive regulation of synapse assembly Source: RGD
  • protein autophosphorylation Source: UniProtKB
  • regulation of protein autophosphorylation Source: Ensembl
  • response to ischemia Source: RGD
  • response to prolactin Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Calcium, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.20. 5301.
ReactomeiR-RNO-166208. mTORC1-mediated signalling.

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic elongation factor 2 kinase (EC:2.7.11.20)
Short name:
eEF-2 kinase
Short name:
eEF-2K
Alternative name(s):
Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase
Gene namesi
Name:Eef2k
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi2538. Eef2k.

Subcellular locationi

GO - Cellular componenti

  • postsynaptic density Source: RGD
Complete GO annotation...

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3325307.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 724723Eukaryotic elongation factor 2 kinasePRO_0000086938Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei18 – 181PhosphoserineBy similarity
Modified residuei27 – 271PhosphoserineBy similarity
Modified residuei70 – 701PhosphoserineBy similarity
Modified residuei73 – 731PhosphoserineCombined sources
Modified residuei77 – 771Phosphoserine; by autocatalysis and TRPM7By similarity
Modified residuei242 – 2421PhosphoserineBy similarity
Modified residuei347 – 3471PhosphothreonineCombined sources
Modified residuei352 – 3521Phosphothreonine; by autocatalysisBy similarity
Modified residuei358 – 3581Phosphoserine; by MAPK13 and CDK1By similarity
Modified residuei365 – 3651PhosphoserineCombined sources
Modified residuei391 – 3911PhosphoserineBy similarity
Modified residuei397 – 3971Phosphoserine; by AMPKBy similarity
Modified residuei434 – 4341PhosphoserineBy similarity
Modified residuei444 – 4441PhosphoserineCombined sources
Modified residuei469 – 4691PhosphoserineCombined sources
Modified residuei473 – 4731PhosphoserineCombined sources
Modified residuei476 – 4761PhosphoserineCombined sources
Modified residuei499 – 4991Phosphoserine; by PKA1 Publication

Post-translational modificationi

The N-terminus is blocked.
Autophosphorylated at multiple residues, Thr-347 being the major site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-397 leading to EEF2K activation and protein synthesis inhibition. Phosphorylated by TRPM7 at Ser-77 resulting in improved protein stability, higher EE2F phosphorylated and subsequently reduced rate of protein synthesis. Phosphorylation by other kinases such as CDK1 and MAPK13 at Ser-358 or RPS6KA1 and RPS6KB1 at Ser-365 instead decrease EEF2K activity and promote protein synthesis (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP70531.
PRIDEiP70531.

PTM databases

iPTMnetiP70531.
PhosphoSiteiP70531.

Expressioni

Tissue specificityi

Mostly in skeletal muscle.

Gene expression databases

GenevisibleiP70531. RN.

Interactioni

Subunit structurei

Monomer or homodimer.Curated

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022726.

Structurei

3D structure databases

ProteinModelPortaliP70531.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini115 – 325211Alpha-type protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni593 – 60917Calmodulin-bindingSequence analysisAdd
BLAST
Regioni609 – 62618Pseudosubstrate/autoinhibitory domainSequence analysisAdd
BLAST

Domaini

The catalytic domain is located to N-terminal region. The neighbor region contains the calmodulin-binding domain (By similarity).By similarity

Sequence similaritiesi

Contains 1 alpha-type protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IFRY. Eukaryota.
ENOG410YE3S. LUCA.
GeneTreeiENSGT00800000124135.
HOGENOMiHOG000022023.
HOVERGENiHBG002318.
InParanoidiP70531.
KOiK08292.
OMAiHEAGRFC.
OrthoDBiEOG7673B0.
PhylomeDBiP70531.
TreeFamiTF316085.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR017400. eEF-2K.
IPR011009. Kinase-like_dom.
IPR004166. MHCK_EF2_kinase.
IPR006597. Sel1-like.
IPR011990. TPR-like_helical_dom.
[Graphical view]
PfamiPF02816. Alpha_kinase. 1 hit.
PF08238. Sel1. 4 hits.
[Graphical view]
PIRSFiPIRSF038139. Elongation_factor_2_kinase. 1 hit.
SMARTiSM00811. Alpha_kinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51158. ALPHA_KINASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P70531-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADEDLIFRL EGVDGGGSSG AGRHGDSDTD SDDDEGYFIC PITDDHMSNQ
60 70 80 90 100
NVNSKGQGYY NNLLKTECGS TGSPASSFHF KEAWKHAIEK AKHMPDPWAE
110 120 130 140 150
FHLEDIATEH ATRHRYNAVT GEWLKDEVLI KMASQPFGRG AMRECFRTKK
160 170 180 190 200
LSNFLHAQHW KGASNYVAKR YLEPVDRSVY FEDVQLQMEA KLWGEEYNRH
210 220 230 240 250
KPPKQVDIMQ MCIIELKDRQ GQPLFHLEHY IEGKYIKYNS NSGFVRDDNI
260 270 280 290 300
RLTPQAFSHF TFERSGHQLI VVDIQGVGDL YTDPQIHTEK GTDFGDGNLG
310 320 330 340 350
VRGMALFFYS HACNRICQSM GLAPFDLSPR EQDAVNQSTK LLQSAKTILR
360 370 380 390 400
GTEEKCGSPR IRTLSGSRPP LLLRLSENSG DENMSDVTFD SLPSSPSSAT
410 420 430 440 450
PHSQKLDHLH WPVFGDLDNM GPRDHDRMDN HRDSENSGDS GYPSEKRSDL
460 470 480 490 500
DDPEPREHGH SNGNRRPESD EDSLGSSGRV CVETWNLLNP SRLHLPRPSA
510 520 530 540 550
VALEVQRLNA LDLGRKIGKS VLGKVHLAMV RYHEGGRFCE KDEEWDQESA
560 570 580 590 600
IFHLEHAADL GELEAIVGLG LMYSQLPHHI LADVSLEETE ENKTKGFDYL
610 620 630 640 650
LKAAEAGDRQ SMILVARAFD TGLNLSPDRC QDWSEALHWY NTALETTDCD
660 670 680 690 700
EGGEYDGIQD EPQYALLARE AEMLLTGGFG LDKNPQRSGD LYTQAAEAAM
710 720
EAMKGRLANQ YYEKAEEAWA QMEE
Length:724
Mass (Da):81,489
Last modified:February 1, 1997 - v1
Checksum:iE4DDD832AE9F7165
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X96426 mRNA. Translation: CAA65286.1.
U93849 mRNA. Translation: AAB58272.1.
RefSeqiNP_037079.1. NM_012947.2.
XP_006230218.1. XM_006230156.2.
XP_006230219.1. XM_006230157.2.
XP_006230220.1. XM_006230158.2.
UniGeneiRn.10958.

Genome annotation databases

EnsembliENSRNOT00000022726; ENSRNOP00000022726; ENSRNOG00000016448.
GeneIDi25435.
KEGGirno:25435.
UCSCiRGD:2538. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X96426 mRNA. Translation: CAA65286.1.
U93849 mRNA. Translation: AAB58272.1.
RefSeqiNP_037079.1. NM_012947.2.
XP_006230218.1. XM_006230156.2.
XP_006230219.1. XM_006230157.2.
XP_006230220.1. XM_006230158.2.
UniGeneiRn.10958.

3D structure databases

ProteinModelPortaliP70531.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000022726.

Chemistry

ChEMBLiCHEMBL3325307.

PTM databases

iPTMnetiP70531.
PhosphoSiteiP70531.

Proteomic databases

PaxDbiP70531.
PRIDEiP70531.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000022726; ENSRNOP00000022726; ENSRNOG00000016448.
GeneIDi25435.
KEGGirno:25435.
UCSCiRGD:2538. rat.

Organism-specific databases

CTDi29904.
RGDi2538. Eef2k.

Phylogenomic databases

eggNOGiENOG410IFRY. Eukaryota.
ENOG410YE3S. LUCA.
GeneTreeiENSGT00800000124135.
HOGENOMiHOG000022023.
HOVERGENiHBG002318.
InParanoidiP70531.
KOiK08292.
OMAiHEAGRFC.
OrthoDBiEOG7673B0.
PhylomeDBiP70531.
TreeFamiTF316085.

Enzyme and pathway databases

BRENDAi2.7.11.20. 5301.
ReactomeiR-RNO-166208. mTORC1-mediated signalling.

Miscellaneous databases

PROiP70531.

Gene expression databases

GenevisibleiP70531. RN.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR017400. eEF-2K.
IPR011009. Kinase-like_dom.
IPR004166. MHCK_EF2_kinase.
IPR006597. Sel1-like.
IPR011990. TPR-like_helical_dom.
[Graphical view]
PfamiPF02816. Alpha_kinase. 1 hit.
PF08238. Sel1. 4 hits.
[Graphical view]
PIRSFiPIRSF038139. Elongation_factor_2_kinase. 1 hit.
SMARTiSM00811. Alpha_kinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51158. ALPHA_KINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of cDNA encoding protein synthesis elongation factor-2 kinase."
    Redpath N.T., Price N.T., Proud C.G.
    J. Biol. Chem. 271:17547-17554(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: New England Deaconess Hospital.
    Tissue: Pheochromocytoma.
  3. "Purification and characterization of calmodulin-dependent protein kinase III from rabbit reticulocytes and rat pancreas."
    Mitsui K., Brady M., Palfrey H.C., Nairn A.C.
    J. Biol. Chem. 268:13422-13433(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: AUTOPHOSPHORYLATION.
  4. "Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity."
    Diggle T.A., Subkhankulova T., Lilley K.S., Shikotra N., Willis A.E., Redpath N.T.
    Biochem. J. 353:621-626(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-499 BY PKA.
  5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73; THR-347; SER-365; SER-444; SER-469; SER-473 AND SER-476, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiEF2K_RAT
AccessioniPrimary (citable) accession number: P70531
Secondary accession number(s): O09089
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 1, 1997
Last modified: July 6, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.