This gene encodes a highly conserved protein kinase in the calmodulin-mediated signaling pathway that links activation of cell surface receptors to cell division. This kinase is involved in the regulation of protein synthesis. It phosphorylates eukaryotic elongation factor 2 (EEF2) and thus inhibits the EEF2 function. The activity of this kinase is increased in many cancers and... See more...

Aliases for EEF2K Gene

Aliases for EEF2K Gene

  • Eukaryotic Elongation Factor 2 Kinase 2 3 4 5
  • EEF-2K 2 3 4
  • EEF-2 Kinase 3 4
  • EC 2.7.11.20 4 51
  • CaMKIII 2 3
  • Calcium/Calmodulin-Dependent Eukaryotic Elongation Factor-2 Kinase 3
  • Calcium/Calmodulin-Dependent Eukaryotic Elongation Factor 2 Kinase 4
  • Calmodulin-Dependent Protein Kinase III 3
  • Eukaroytic Elongation Factor 2 Kinase 3
  • Elongation Factor-2 Kinase 3
  • Alternative Protein EEF2K 3
  • EC 2.7.11 51
  • HSU93850 3
  • EEF2K 5

External Ids for EEF2K Gene

Previous GeneCards Identifiers for EEF2K Gene

  • GC16P021638
  • GC16P022227
  • GC16P022184
  • GC00U916980
  • GC16P022125
  • GC16P020462

Summaries for EEF2K Gene

Entrez Gene Summary for EEF2K Gene

  • This gene encodes a highly conserved protein kinase in the calmodulin-mediated signaling pathway that links activation of cell surface receptors to cell division. This kinase is involved in the regulation of protein synthesis. It phosphorylates eukaryotic elongation factor 2 (EEF2) and thus inhibits the EEF2 function. The activity of this kinase is increased in many cancers and may be a valid target for anti-cancer treatment. [provided by RefSeq, Jul 2008]

GeneCards Summary for EEF2K Gene

EEF2K (Eukaryotic Elongation Factor 2 Kinase) is a Protein Coding gene. Diseases associated with EEF2K include Anoxia and Chief Cell Adenoma. Among its related pathways are Translation Translation regulation by Alpha-1 adrenergic receptors and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include calcium ion binding and protein kinase activity. An important paralog of this gene is HSPA12B.

UniProtKB/Swiss-Prot Summary for EEF2K Gene

  • 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.

Tocris Summary for EEF2K Gene

  • Calmodulin-dependent kinases (CaMK) are a family of serine/threonine kinases that mediate many of the second messenger effects of Ca2+. At basal Ca2+ levels, CaMKs are maintained in a dormant state through autoinhibition, which can be relieved by increases in Ca2+ levels.

Gene Wiki entry for EEF2K Gene

Additional gene information for EEF2K Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EEF2K Gene

Genomics for EEF2K Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for EEF2K Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EEF2K on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for EEF2K

Top Transcription factor binding sites by QIAGEN in the EEF2K gene promoter:
  • AP-2alpha
  • AP-2alphaA
  • FOXO1
  • FOXO1a
  • Pbx1a
  • SRY
  • STAT1
  • STAT1alpha
  • STAT1beta
  • ZID

Genomic Locations for EEF2K Gene

Genomic Locations for EEF2K Gene
chr16:22,206,278-22,288,738
(GRCh38/hg38)
Size:
82,461 bases
Orientation:
Plus strand
chr16:22,217,592-22,300,066
(GRCh37/hg19)
Size:
82,475 bases
Orientation:
Plus strand

Genomic View for EEF2K Gene

Genes around EEF2K on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EEF2K Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EEF2K Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EEF2K Gene

Proteins for EEF2K Gene

  • Protein details for EEF2K Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00418-EF2K_HUMAN
    Recommended name:
    Eukaryotic elongation factor 2 kinase
    Protein Accession:
    O00418
    Secondary Accessions:
    • Q8N588

    Protein attributes for EEF2K Gene

    Size:
    725 amino acids
    Molecular mass:
    82144 Da
    Quaternary structure:
    • Monomer or homodimer (Probable). Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (PubMed:11015200).

    Three dimensional structures from OCA and Proteopedia for EEF2K Gene

neXtProt entry for EEF2K Gene

Selected DME Specific Peptides for EEF2K Gene

O00418:
  • DIQGVGD
  • IEGKYIKYNSNSGFV
  • TPQAFSHF
  • RLTPQAFSHFTFERSGHQ

Post-translational modifications for EEF2K Gene

  • 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.
  • Ubiquitination at Lys65, Lys162, Lys238, Lys341, Lys347, Lys485, Lys603, and Lys705
  • Modification sites at PhosphoSitePlus

Other Protein References for EEF2K Gene

Domains & Families for EEF2K Gene

Gene Families for EEF2K Gene

Protein Domains for EEF2K Gene

InterPro:
Blocks:
  • MHCK/EF2 kinase domain
  • Sel1-like repeat
ProtoNet:

Suggested Antigen Peptide Sequences for EEF2K Gene

GenScript: Design optimal peptide antigens:
  • Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase (EF2K_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O00418

UniProtKB/Swiss-Prot:

EF2K_HUMAN :
  • Belongs to the protein kinase superfamily. Alpha-type protein kinase family.
Family:
  • Belongs to the protein kinase superfamily. Alpha-type protein kinase family.
genes like me logo Genes that share domains with EEF2K: view

Function for EEF2K Gene

Molecular function for EEF2K Gene

UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[translation elongation factor 2] + ATP = [translation elongation factor 2]-phosphate + ADP + H(+); Xref=Rhea:RHEA:21436, Rhea:RHEA-COMP:11268, Rhea:RHEA-COMP:11269, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216; EC=2.7.11.20; Evidence={ECO:0000269|PubMed:11015200, ECO:0000269|PubMed:9144159};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.2 uM for EEF2 {ECO:0000269|PubMed:11015200}; Vmax=4 nmol/min/mg enzyme {ECO:0000269|PubMed:11015200};
UniProtKB/Swiss-Prot EnzymeRegulation:
Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent.

Enzyme Numbers (IUBMB) for EEF2K Gene

Phenotypes From GWAS Catalog for EEF2K Gene

Gene Ontology (GO) - Molecular Function for EEF2K Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity TAS 9144159
GO:0004674 protein serine/threonine kinase activity IEA --
GO:0004686 elongation factor-2 kinase activity IDA 9144159
GO:0005509 calcium ion binding IEA --
genes like me logo Genes that share ontologies with EEF2K: view
genes like me logo Genes that share phenotypes with EEF2K: view

Animal Models for EEF2K Gene

MGI Knock Outs for EEF2K:

Animal Model Products

CRISPR Products

miRNA for EEF2K Gene

miRTarBase miRNAs that target EEF2K

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EEF2K

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EEF2K Gene

Localization for EEF2K Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EEF2K gene
Compartment Confidence
cytosol 5
nucleus 3
extracellular 2
cytoskeleton 2
mitochondrion 2
plasma membrane 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for EEF2K Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS 9144159
GO:0005829 cytosol TAS --
GO:0014069 postsynaptic density IEA --
GO:0043197 dendritic spine IEA --
genes like me logo Genes that share ontologies with EEF2K: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for EEF2K Gene

Pathways & Interactions for EEF2K Gene

genes like me logo Genes that share pathways with EEF2K: view

Pathways by source for EEF2K Gene

3 GeneGo (Thomson Reuters) pathways for EEF2K Gene
  • Regulation of lipid metabolism Insulin signaling-generic cascades
  • Translation Insulin regulation of translation
  • Translation Translation regulation by Alpha-1 adrenergic receptors
2 Qiagen pathways for EEF2K Gene
  • Insulin Receptor Pathway
  • p70S6K Signaling
1 Cell Signaling Technology pathway for EEF2K Gene
1 GeneTex pathway for EEF2K Gene

SIGNOR curated interactions for EEF2K Gene

Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for EEF2K Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002931 response to ischemia IEA --
GO:0006414 translational elongation TAS 9144159
GO:0006468 protein phosphorylation IEA --
GO:0016310 phosphorylation IEA --
GO:0031952 regulation of protein autophosphorylation IEA --
genes like me logo Genes that share ontologies with EEF2K: view

Drugs & Compounds for EEF2K Gene

(14) Drugs for EEF2K Gene - From: ApexBio, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
A 484954 Pharma EEF2K Inhibitor, CaM kinase III (eEF-2 kinase) inhibitor 0
NH125 Pharma Selective eEF-2 kinase inhibitor, CaM kinase III (eEF-2 kinase) inhibitor 0
Calcium Nutra 6556

(4) Additional Compounds for EEF2K Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Autocamtide-2-related inhibitory peptide, myristoylated
201422-04-0
KN 93
139298-40-1

(4) Tocris Compounds for EEF2K Gene

Compound Action Cas Number
A 484954 CaM kinase III (eEF-2 kinase) inhibitor 142557-61-7
Autocamtide-2-related inhibitory peptide, myristoylated CaM kinase II inhibitor; enhanced cell permeable derivative of Autocamtide-2-related inhibitory peptide 201422-04-0
KN 93 CaM kinase II inhibitor; also K+ channel blocker (KV) 139298-40-1
NH 125 CaM kinase III (eEF-2 kinase) inhibitor 278603-08-0

(2) ApexBio Compounds for EEF2K Gene

Compound Action Cas Number
A 484954 EEF2K Inhibitor 142557-61-7
NH125 Selective eEF-2 kinase inhibitor 278603-08-0
genes like me logo Genes that share compounds with EEF2K: view

Drug Products

Transcripts for EEF2K Gene

mRNA/cDNA for EEF2K Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EEF2K

Alternative Splicing Database (ASD) splice patterns (SP) for EEF2K Gene

No ASD Table

Relevant External Links for EEF2K Gene

GeneLoc Exon Structure for
EEF2K

Expression for EEF2K Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for EEF2K Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EEF2K Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (x4.1).

Protein differential expression in normal tissues from HIPED for EEF2K Gene

This gene is overexpressed in Liver, secretome (19.2), Lung (8.9), and Prostate (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for EEF2K Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for EEF2K

SOURCE GeneReport for Unigene cluster for EEF2K Gene:

Hs.498892

Evidence on tissue expression from TISSUES for EEF2K Gene

  • Liver(4.3)
  • Nervous system(2.8)
  • Skin(2.6)
  • Muscle(2.2)
  • Heart(2.1)
genes like me logo Genes that share expression patterns with EEF2K: view

No data available for Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for EEF2K Gene

Orthologs for EEF2K Gene

This gene was present in the common ancestor of animals.

Orthologs for EEF2K Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia EEF2K 30 31
  • 99.36 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia EEF2K 30 31
  • 89.56 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia EEF2K 30 31
  • 88.8 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Eef2k 30 17 31
  • 85.91 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Eef2k 30
  • 85.73 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia EEF2K 31
  • 85 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia EEF2K 31
  • 84 (a)
OneToOne
Chicken
(Gallus gallus)
Aves EEF2K 30 31
  • 74.25 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia EEF2K 31
  • 71 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia eef2k 30
  • 69.92 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.18633 30
Zebrafish
(Danio rerio)
Actinopterygii eef2k 30 31
  • 66.31 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea efk-1 30 31 32
  • 49.28 (n)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 44 (a)
ManyToMany
CSA.7709 31
  • 43 (a)
ManyToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.10624 30
Species where no ortholog for EEF2K was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for EEF2K Gene

ENSEMBL:
Gene Tree for EEF2K (if available)
TreeFam:
Gene Tree for EEF2K (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EEF2K: view image

Paralogs for EEF2K Gene

Paralogs for EEF2K Gene

genes like me logo Genes that share paralogs with EEF2K: view

Variants for EEF2K Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for EEF2K Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
rs147978363 A colorectal adenocarcinoma sample p.Thr291Met
rs17841292 - p.Pro75Ala
rs4783453 - p.Gln361Arg
rs56137739 - p.Arg433Trp
rs9935059 - p.His23Arg

Additional dbSNP identifiers (rs#s) for EEF2K Gene

Structural Variations from Database of Genomic Variants (DGV) for EEF2K Gene

Variant ID Type Subtype PubMed ID
dgv3n1 OTHER inversion 15895083
dgv47n16 OTHER inversion 17901297
esv2662229 CNV deletion 23128226
esv2758637 CNV gain+loss 17122850
esv3368991 OTHER inversion 20981092
esv3638195 CNV gain 21293372
esv998989 OTHER inversion 20482838
nsv1077770 OTHER inversion 25765185
nsv1140248 OTHER inversion 24896259
nsv469818 CNV loss 16826518
nsv499139 OTHER inversion 21111241
nsv7280 OTHER inversion 18451855

Variation tolerance for EEF2K Gene

Residual Variation Intolerance Score: 46.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.91; 79.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EEF2K Gene

Human Gene Mutation Database (HGMD)
EEF2K
SNPedia medical, phenotypic, and genealogical associations of SNPs for
EEF2K

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EEF2K Gene

Disorders for EEF2K Gene

MalaCards: The human disease database

(3) MalaCards diseases for EEF2K Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
anoxia
chief cell adenoma
  • chief cell adenoma of parathyroid gland
lung cancer
  • adenocarcinoma of lung
- elite association - COSMIC cancer census association via MalaCards
Search EEF2K in MalaCards View complete list of genes associated with diseases

Additional Disease Information for EEF2K

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with EEF2K: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EEF2K Gene

Publications for EEF2K Gene

  1. Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase. (PMID: 9144159) Ryazanov AG … Hait WN (Proceedings of the National Academy of Sciences of the United States of America 1997) 2 3 4 23
  2. 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. (PMID: 14709557) Browne GJ … Proud CG (The Journal of biological chemistry 2004) 3 4 23
  3. A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. (PMID: 11500363) Knebel A … Cohen P (The EMBO journal 2001) 3 4 23
  4. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. (PMID: 11500364) Wang X … Proud CG (The EMBO journal 2001) 3 4 23
  5. Mapping the functional domains of elongation factor-2 kinase. (PMID: 11015200) Pavur KS … Ryazanov AG (Biochemistry 2000) 3 4 23

Products for EEF2K Gene

  • Addgene plasmids for EEF2K

Sources for EEF2K Gene