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Protein

Eukaryotic elongation factor 2 kinase

Gene

Eef2k

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Nucleotide bindingi295 – 301ATPBy similarity7

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

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Calcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi2538 Eef2k

Subcellular locationi

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3325307

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000869382 – 724Eukaryotic elongation factor 2 kinaseAdd BLAST723

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei18PhosphoserineBy similarity1
Modified residuei27PhosphoserineBy similarity1
Modified residuei70PhosphoserineBy similarity1
Modified residuei73PhosphoserineCombined sources1
Modified residuei77Phosphoserine; by autocatalysis and TRPM7By similarity1
Modified residuei242PhosphoserineBy similarity1
Modified residuei347PhosphothreonineCombined sources1
Modified residuei352Phosphothreonine; by autocatalysisBy similarity1
Modified residuei358Phosphoserine; by MAPK13 and CDK1By similarity1
Modified residuei365PhosphoserineCombined sources1
Modified residuei391PhosphoserineBy similarity1
Modified residuei397Phosphoserine; by AMPKBy similarity1
Modified residuei434PhosphoserineBy similarity1
Modified residuei444PhosphoserineCombined sources1
Modified residuei469PhosphoserineCombined sources1
Modified residuei473PhosphoserineCombined sources1
Modified residuei476PhosphoserineCombined sources1
Modified residuei499Phosphoserine; by PKA1 Publication1

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
PhosphoSitePlusiP70531

Expressioni

Tissue specificityi

Widely expressed, with high levels in reticulocytes and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSRNOG00000016448
GenevisibleiP70531 RN

Interactioni

Subunit structurei

Monomer or homodimer (Probable). Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (By similarity).By similarityCurated

GO - Molecular functioni

Protein-protein interaction databases

ELMiP70531
STRINGi10116.ENSRNOP00000022726

Structurei

3D structure databases

ProteinModelPortaliP70531
SMRiP70531
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini115 – 325Alpha-type protein kinasePROSITE-ProRule annotationAdd BLAST211

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni80 – 93Calmodulin-bindingBy similarityAdd BLAST14

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IFRY Eukaryota
ENOG410YE3S LUCA
GeneTreeiENSGT00800000124135
HOGENOMiHOG000022023
HOVERGENiHBG002318
InParanoidiP70531
KOiK08292
OMAiFICPITD
OrthoDBiEOG091G09CK
PhylomeDBiP70531
TreeFamiTF316085

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR017400 eEF-2K
IPR011009 Kinase-like_dom_sf
IPR004166 MHCK_EF2_kinase
IPR006597 Sel1-like
IPR011990 TPR-like_helical_dom_sf
PfamiView protein in Pfam
PF02816 Alpha_kinase, 1 hit
PF08238 Sel1, 4 hits
PIRSFiPIRSF038139 Elongation_factor_2_kinase, 1 hit
SMARTiView protein in SMART
SM00811 Alpha_kinase, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51158 ALPHA_KINASE, 1 hit

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_006230156.3
XP_006230219.1, XM_006230157.3
XP_006230220.1, XM_006230158.3
UniGeneiRn.10958

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiEF2K_RAT
AccessioniPrimary (citable) accession number: P70531
Secondary accession number(s): O09089
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 1, 1997
Last modified: May 23, 2018
This is version 141 of the entry and version 1 of the sequence. See 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

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