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Protein

Eukaryotic elongation factor 2 kinase

Gene

Eef2k

Organism
Mus musculus (Mouse)
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.1 Publication

Catalytic activityi

ATP + [elongation factor 2] = ADP + [elongation factor 2] phosphate.1 Publication

Enzyme regulationi

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

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: UniProtKB
  • translation factor activity, RNA binding Source: UniProtKB

GO - Biological processi

  • protein autophosphorylation Source: MGI
  • regulation of protein autophosphorylation Source: UniProtKB
  • translational elongation Source: UniProtKB
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. 3474.
ReactomeiREACT_283781. S6K1 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1195261. Eef2k.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 724723Eukaryotic elongation factor 2 kinasePRO_0000086937Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei27 – 271PhosphoserineBy similarity
Modified residuei61 – 611Phosphoserine; by autocatalysisBy similarity
Modified residuei70 – 701Phosphoserine1 Publication
Modified residuei77 – 771Phosphoserine; by autocatalysis and TRPM7By similarity
Modified residuei347 – 3471Phosphothreonine; by autocatalysisBy similarity
Modified residuei352 – 3521Phosphothreonine; by autocatalysisBy similarity
Modified residuei358 – 3581Phosphoserine; by MAPK13 and CDK1By similarity
Modified residuei365 – 3651Phosphoserine; by autocatalysis, RPS6KA1 and RPS6KB1By similarity
Modified residuei397 – 3971Phosphoserine; by AMPKBy similarity
Modified residuei444 – 4441Phosphoserine; by autocatalysisBy similarity
Modified residuei469 – 4691PhosphoserineBy similarity
Modified residuei473 – 4731Phosphoserine; by autocatalysisBy similarity
Modified residuei476 – 4761PhosphoserineBy similarity
Modified residuei499 – 4991Phosphoserine; by PKABy similarity

Post-translational modificationi

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

MaxQBiO08796.
PaxDbiO08796.
PRIDEiO08796.

PTM databases

PhosphoSiteiO08796.

Expressioni

Tissue specificityi

Ubiquitously expressed. Particularly abundant in skeletal muscle and heart.

Gene expression databases

BgeeiO08796.
CleanExiMM_EEF2K.
ExpressionAtlasiO08796. baseline and differential.
GenevestigatoriO08796.

Interactioni

Subunit structurei

Monomer or homodimer.Curated

Structurei

3D structure databases

ProteinModelPortaliO08796.
SMRiO08796. Positions 116-322.
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

eggNOGiNOG145133.
GeneTreeiENSGT00790000123102.
HOGENOMiHOG000022023.
HOVERGENiHBG002318.
InParanoidiO08796.
KOiK08292.
OMAiQIHTETG.
OrthoDBiEOG7673B0.
PhylomeDBiO08796.
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.

O08796-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADEDLIFCL EGVDGGRCSR AGHNADSDTD SDDDEGYFIC PITDDHMSNQ
60 70 80 90 100
NVSSKVQSYY SNLTKTECGS TGSPASSFHF KEAWKHAIEK AKHMPDPWAE
110 120 130 140 150
FHLEDIATEH ATRHRYNAVT GEWLKDEVLI KMASQPFGRG AMRECFRTKK
160 170 180 190 200
LSNFLHAQQW KGASNYVAKR YIEPVDRSVY FEDVQLQMEA KLWGEDYNRH
210 220 230 240 250
KPPKQVDIMQ MCIIELKDRP GQPLFHLEHY IEGKYIKYNS NSGFVRDDNI
260 270 280 290 300
RLTPQAFSHF TFERSGHQLI VVDIQGVGDL YTDPQIHTEK GTDFGDGNLG
310 320 330 340 350
VRGMALFFYS HACNRICQSM GLTPFDLSPR EQDAVNQSTR LLQSAKTILR
360 370 380 390 400
GTEEKCGSPR IRTLSSSRPP LLLRLSENSG DENMSDVTFD SLPSSPSSAT
410 420 430 440 450
PHSQKLDHLH WPVFGDLDNM GPRDHDRMDN HRDSENSGDS GYPSEKRSDL
460 470 480 490 500
DDPEPREHGH SNGNRRHESD EDSLGSSGRV CVETWNLLNP SRLHLPRPSA
510 520 530 540 550
VALEVQRLNA LDLGRKIGKS VLGKVHLAMV RYHEGGRFCE KDEEWDRESA
560 570 580 590 600
IFHLEHAADL GELEAIVGLG LMYSQLPHHI LADVSLKETE ENKTKGFDYL
610 620 630 640 650
LKAAEAGDRH SMILVARAFD TGLNLSPDRC QDWSEALHWY NTALETTDCD
660 670 680 690 700
EGGEYDGIQD EPQYALLARE AEMLLTGGFG LDKNPQRSGD LYTQAAEAAM
710 720
EAMKGRLANQ YYEKAEEAWA QMEE
Length:724
Mass (Da):81,739
Last modified:July 1, 1997 - v1
Checksum:iB892D7D547C8E7AE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93848 mRNA. Translation: AAB58271.1.
BC003433 mRNA. Translation: AAH03433.1.
CCDSiCCDS21796.1.
RefSeqiNP_001254639.1. NM_001267710.1.
NP_001254640.1. NM_001267711.1.
NP_031934.1. NM_007908.4.
XP_006507405.1. XM_006507342.2.
XP_006507406.1. XM_006507343.2.
UniGeneiMm.25997.
Mm.470116.

Genome annotation databases

EnsembliENSMUST00000047875; ENSMUSP00000046595; ENSMUSG00000035064.
ENSMUST00000106488; ENSMUSP00000102097; ENSMUSG00000035064.
ENSMUST00000106489; ENSMUSP00000102098; ENSMUSG00000035064.
GeneIDi13631.
KEGGimmu:13631.
UCSCiuc009jnb.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93848 mRNA. Translation: AAB58271.1.
BC003433 mRNA. Translation: AAH03433.1.
CCDSiCCDS21796.1.
RefSeqiNP_001254639.1. NM_001267710.1.
NP_001254640.1. NM_001267711.1.
NP_031934.1. NM_007908.4.
XP_006507405.1. XM_006507342.2.
XP_006507406.1. XM_006507343.2.
UniGeneiMm.25997.
Mm.470116.

3D structure databases

ProteinModelPortaliO08796.
SMRiO08796. Positions 116-322.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiO08796.

Proteomic databases

MaxQBiO08796.
PaxDbiO08796.
PRIDEiO08796.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047875; ENSMUSP00000046595; ENSMUSG00000035064.
ENSMUST00000106488; ENSMUSP00000102097; ENSMUSG00000035064.
ENSMUST00000106489; ENSMUSP00000102098; ENSMUSG00000035064.
GeneIDi13631.
KEGGimmu:13631.
UCSCiuc009jnb.2. mouse.

Organism-specific databases

CTDi29904.
MGIiMGI:1195261. Eef2k.

Phylogenomic databases

eggNOGiNOG145133.
GeneTreeiENSGT00790000123102.
HOGENOMiHOG000022023.
HOVERGENiHBG002318.
InParanoidiO08796.
KOiK08292.
OMAiQIHTETG.
OrthoDBiEOG7673B0.
PhylomeDBiO08796.
TreeFamiTF316085.

Enzyme and pathway databases

BRENDAi2.7.11.20. 3474.
ReactomeiREACT_283781. S6K1 signalling.

Miscellaneous databases

NextBioi284316.
PROiO08796.
SOURCEiSearch...

Gene expression databases

BgeeiO08796.
CleanExiMM_EEF2K.
ExpressionAtlasiO08796. baseline and differential.
GenevestigatoriO08796.

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. Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION.
    Strain: BALB/c.
    Tissue: Spleen.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Czech II.
    Tissue: Mammary gland.
  3. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiEF2K_MOUSE
AccessioniPrimary (citable) accession number: O08796
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 1, 1997
Last modified: May 27, 2015
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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.