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
Homo sapiens (Human)
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.2 Publications

Catalytic activityi

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

Activity regulationi

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

Kineticsi

  1. KM=1.2 µM for EEF21 Publication
  1. Vmax=4 nmol/min/mg enzyme1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi296 – 302ATPBy similarity7

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calcium ion binding Source: InterPro
  • calmodulin binding Source: UniProtKB
  • elongation factor-2 kinase activity Source: UniProtKB
  • protein kinase activity Source: ProtInc
  • translation factor activity, RNA binding Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Calcium, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.20 2681
ReactomeiR-HSA-166208 mTORC1-mediated signalling
SIGNORiO00418

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic elongation factor 2 kinase (EC:2.7.11.202 Publications)
Short name:
eEF-2 kinase
Short name:
eEF-2K
Alternative name(s):
Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase
Gene namesi
Name:EEF2K
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103319.11
HGNCiHGNC:24615 EEF2K
MIMi606968 gene
neXtProtiNX_O00418

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi78S → A: Decreased kinase activity. 1 Publication1
Mutagenesisi348T → A: Decreased kinase activity. 1 Publication1
Mutagenesisi366S → A: Abrogates phosphorylation by RPS6KB1. 2 Publications1
Mutagenesisi366S → A: Decreased kinase activity. 2 Publications1

Organism-specific databases

DisGeNETi101930123
29904
OpenTargetsiENSG00000103319
PharmGKBiPA134992891

Chemistry databases

ChEMBLiCHEMBL5026
GuidetoPHARMACOLOGYi2014

Polymorphism and mutation databases

BioMutaiEEF2K

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000869362 – 725Eukaryotic elongation factor 2 kinaseAdd BLAST724

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei18PhosphoserineCombined sources1
Modified residuei27PhosphoserineCombined sources1
Modified residuei61Phosphoserine; by autocatalysis1 Publication1
Modified residuei66Phosphoserine; by autocatalysis1 Publication1
Modified residuei70PhosphoserineCombined sources1
Modified residuei71PhosphoserineBy similarity1
Modified residuei72PhosphoserineCombined sources1
Modified residuei74PhosphoserineCombined sources1
Modified residuei78Phosphoserine; by autocatalysis and TRPM7Combined sources2 Publications1
Modified residuei243PhosphoserineCombined sources1
Modified residuei348Phosphothreonine; by autocatalysisCombined sources1 Publication1
Modified residuei353Phosphothreonine; by autocatalysisCombined sources1 Publication1
Modified residuei359Phosphoserine; by MAPK13 and CDK12 Publications1
Modified residuei366Phosphoserine; by autocatalysis, RPS6KA1 and RPS6KB12 Publications1
Modified residuei392PhosphoserineBy similarity1
Modified residuei398Phosphoserine; by AMPK1 Publication1
Modified residuei435PhosphoserineCombined sources1
Modified residuei445Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei470PhosphoserineCombined sources1
Modified residuei474Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei477PhosphoserineCombined sources1
Modified residuei491Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei500Phosphoserine; by PKABy similarity1

Post-translational modificationi

Autophosphorylated at multiple residues, Thr-348 being the major site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-398 leading to EEF2K activation and protein synthesis inhibition. Phosphorylated by TRPM7 at Ser-78 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-359 or RPS6KA1 and RPS6KB1 at Ser-366 instead decrease EEF2K activity and promote protein synthesis.7 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO00418
MaxQBiO00418
PaxDbiO00418
PeptideAtlasiO00418
PRIDEiO00418
ProteomicsDBi47876

PTM databases

iPTMnetiO00418
PhosphoSitePlusiO00418

Expressioni

Gene expression databases

BgeeiENSG00000103319 Expressed in 204 organ(s), highest expression level in quadriceps femoris
CleanExiHS_EEF2K
ExpressionAtlasiO00418 baseline and differential
GenevisibleiO00418 HS

Organism-specific databases

HPAiCAB007818
HPA056061

Interactioni

Subunit structurei

Monomer or homodimer (Probable). Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (PubMed:11015200).Curated1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118953, 34 interactors
ELMiO00418
IntActiO00418, 12 interactors
MINTiO00418
STRINGi9606.ENSP00000263026

Chemistry databases

BindingDBiO00418

Structurei

Secondary structure

1725
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO00418
SMRiO00418
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini116 – 326Alpha-type protein kinasePROSITE-ProRule annotationAdd BLAST211

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni81 – 94Calmodulin-binding1 PublicationAdd BLAST14

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IFRY Eukaryota
ENOG410YE3S LUCA
GeneTreeiENSGT00800000124135
HOGENOMiHOG000022023
HOVERGENiHBG002318
InParanoidiO00418
KOiK08292
OMAiACNRICK
OrthoDBiEOG091G09CK
PhylomeDBiO00418
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, 3 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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

O00418-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MADEDLIFRL EGVDGGQSPR AGHDGDSDGD SDDEEGYFIC PITDDPSSNQ
60 70 80 90 100
NVNSKVNKYY SNLTKSERYS SSGSPANSFH FKEAWKHAIQ KAKHMPDPWA
110 120 130 140 150
EFHLEDIATE RATRHRYNAV TGEWLDDEVL IKMASQPFGR GAMRECFRTK
160 170 180 190 200
KLSNFLHAQQ WKGASNYVAK RYIEPVDRDV YFEDVRLQME AKLWGEEYNR
210 220 230 240 250
HKPPKQVDIM QMCIIELKDR PGKPLFHLEH YIEGKYIKYN SNSGFVRDDN
260 270 280 290 300
IRLTPQAFSH FTFERSGHQL IVVDIQGVGD LYTDPQIHTE TGTDFGDGNL
310 320 330 340 350
GVRGMALFFY SHACNRICES MGLAPFDLSP RERDAVNQNT KLLQSAKTIL
360 370 380 390 400
RGTEEKCGSP QVRTLSGSRP PLLRPLSENS GDENMSDVTF DSLPSSPSSA
410 420 430 440 450
TPHSQKLDHL HWPVFSDLDN MASRDHDHLD NHRESENSGD SGYPSEKRGE
460 470 480 490 500
LDDPEPREHG HSYSNRKYES DEDSLGSSGR VCVEKWNLLN SSRLHLPRAS
510 520 530 540 550
AVALEVQRLN ALDLEKKIGK SILGKVHLAM VRYHEGGRFC EKGEEWDQES
560 570 580 590 600
AVFHLEHAAN LGELEAIVGL GLMYSQLPHH ILADVSLKET EENKTKGFDY
610 620 630 640 650
LLKAAEAGDR QSMILVARAF DSGQNLSPDR CQDWLEALHW YNTALEMTDC
660 670 680 690 700
DEGGEYDGMQ DEPRYMMLAR EAEMLFTGGY GLEKDPQRSG DLYTQAAEAA
710 720
MEAMKGRLAN QYYQKAEEAW AQMEE
Length:725
Mass (Da):82,144
Last modified:July 28, 2009 - v2
Checksum:i9D2900E50EFF12DA
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BRH4H3BRH4_HUMAN
Eukaryotic elongation factor 2 kina...
EEF2K
412Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03391523H → R2 PublicationsCorresponds to variant dbSNP:rs9935059Ensembl.1
Natural variantiVAR_03391675P → A1 PublicationCorresponds to variant dbSNP:rs17841292Ensembl.1
Natural variantiVAR_041534291T → M in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs147978363Ensembl.1
Natural variantiVAR_058405361Q → R2 PublicationsCorresponds to variant dbSNP:rs4783453Ensembl.1
Natural variantiVAR_041535433R → W1 PublicationCorresponds to variant dbSNP:rs56137739Ensembl.1
Natural variantiVAR_041536609D → H1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93850 mRNA Translation: AAB58270.1
AC009034 Genomic DNA No translation available.
BC032665 mRNA Translation: AAH32665.1
CCDSiCCDS10604.1
RefSeqiNP_037434.1, NM_013302.3
XP_005276554.1, XM_005276497.3
XP_016878682.1, XM_017023193.1
UniGeneiHs.498892

Genome annotation databases

EnsembliENST00000263026; ENSP00000263026; ENSG00000103319
GeneIDi29904
KEGGihsa:29904
UCSCiuc002dki.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93850 mRNA Translation: AAB58270.1
AC009034 Genomic DNA No translation available.
BC032665 mRNA Translation: AAH32665.1
CCDSiCCDS10604.1
RefSeqiNP_037434.1, NM_013302.3
XP_005276554.1, XM_005276497.3
XP_016878682.1, XM_017023193.1
UniGeneiHs.498892

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5J8HNMR-B74-100[»]
5KS5NMR-A627-725[»]
ProteinModelPortaliO00418
SMRiO00418
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118953, 34 interactors
ELMiO00418
IntActiO00418, 12 interactors
MINTiO00418
STRINGi9606.ENSP00000263026

Chemistry databases

BindingDBiO00418
ChEMBLiCHEMBL5026
GuidetoPHARMACOLOGYi2014

PTM databases

iPTMnetiO00418
PhosphoSitePlusiO00418

Polymorphism and mutation databases

BioMutaiEEF2K

Proteomic databases

EPDiO00418
MaxQBiO00418
PaxDbiO00418
PeptideAtlasiO00418
PRIDEiO00418
ProteomicsDBi47876

Protocols and materials databases

DNASUi29904
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263026; ENSP00000263026; ENSG00000103319
GeneIDi29904
KEGGihsa:29904
UCSCiuc002dki.4 human

Organism-specific databases

CTDi29904
DisGeNETi101930123
29904
EuPathDBiHostDB:ENSG00000103319.11
GeneCardsiEEF2K
HGNCiHGNC:24615 EEF2K
HPAiCAB007818
HPA056061
MIMi606968 gene
neXtProtiNX_O00418
OpenTargetsiENSG00000103319
PharmGKBiPA134992891
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFRY Eukaryota
ENOG410YE3S LUCA
GeneTreeiENSGT00800000124135
HOGENOMiHOG000022023
HOVERGENiHBG002318
InParanoidiO00418
KOiK08292
OMAiACNRICK
OrthoDBiEOG091G09CK
PhylomeDBiO00418
TreeFamiTF316085

Enzyme and pathway databases

BRENDAi2.7.11.20 2681
ReactomeiR-HSA-166208 mTORC1-mediated signalling
SIGNORiO00418

Miscellaneous databases

ChiTaRSiEEF2K human
GeneWikiiEEF2K
PROiPR:O00418
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103319 Expressed in 204 organ(s), highest expression level in quadriceps femoris
CleanExiHS_EEF2K
ExpressionAtlasiO00418 baseline and differential
GenevisibleiO00418 HS

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, 3 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
ProtoNetiSearch...

Entry informationi

Entry nameiEF2K_HUMAN
AccessioniPrimary (citable) accession number: O00418
Secondary accession number(s): Q8N588
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 28, 2009
Last modified: November 7, 2018
This is version 179 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again