EEF2K (eukaryotic elongation factor 2 kinase)

2016-01-01   Bulent Ozpolat , Ozgur Ozkayar 

University of Texas-Houston-MD Anderson Cancer Center, Department of Experimental Therapeutics, 1515 Holcombe Boulevard, Unit 422, Houston, TX7730;




Eukaryotic elongation factor 2 kinase (eEF-2K) (also known as Calmodulin (CaM)-dependent elongation factor 2 kinase,CaMKIII) is an unusual calcium\/calmodulin (Ca2+<\/sup>\/CaM)-dependent Threonin kinase that controls the rate of the elongation phase of protein synthesis through phosphorylating elongation factor 2 (eEF2) (Nairn et al., 1985; Ryazanov 1987; Mitsui et al., 1993; Redpath et al., 1993). Phosphorylation of eEF2 on Thr-56 disrupts the interaction between eEF-2 and the ribosome, leading to reduced protein synthesis. eEF-2K is regulated by phosphorylation by multiple signaling pathways and kinases at 11 different phosphorylation sides (Ryazanov et al., 1988; Carlberg et al., 1990; Abramczyk et al., 2011; Browne et al., 2004; Marshall et al., 2012; Chafouleas et al., 1981; Bowden et al., 2013). Hypoxia, nutrient deprivation and metabolic stress are all known to stimulate eEF-2K through activation of AMPK (Chafouleas et al., 1981).The activity of eEF-2K is increased in rapidly proliferating malignant cells and in cancer specimens, but is absent in normal adjacent tissues (Ashour et al., 2014b). eEF-2K promotes cell proliferation, invasion and tumorigenesis of some cancers. eEF-2K expression (mRNA) correlates with poor patient survival and prognosis (outcome) in some solid tumors, including breast , pancreatic cancer and glioblastoma (Meric-Bernstam et al., 2012). The activity of this kinase is increased in many cancers and may be a potential therapeutic target in some cancers.



EEF2K gene encodes a Ca2+/calmodulin-dependent kinase known as eukaryotic elongation factor-2 kinase (EEF2K).


The EEF2K gene is composed of 18 exons. It spans approximately 80.35 kb of genomic DNA.


This gene encodes 5 transcripts and protein coding transcript (EEF2K-001) has 7388 bp length and this is composed of 725 aa residues. EEF2K-002 is a non sense mediated decay. Other three transcripts (EEF2K-003, -004, -005) do not give rise to proteins.


No pseudogene reported.


Atlas Image
Structure of eukaryotic elongation factor-2 kinase (EF2K) protein. CaM: Calmoduline.


Human eukaryotic elongation factor-2 kinase is composed of 725 amino acids (105 KDa) alfa-kinase catalytic domain of this protein is located at the section of 76-356. Calmoduline (CaM) binding domain is located close to N-terminal and next to the catalytic domain. The function of the region located N-terminal of the CaM-binding site is not well understood but removal of this segment leads to intrinsic autophosphorylation and activity; cause inhibitory effect on the EF2K activity. Contain 18 phosphorylation sites. Autophosphorylated at multiple residues, Thr-348 is the major site. Towards the C-terminal region, there are four predicted alfa-helical regions, and these resemble SEL-1-type repeats. The region lies between SEL-1 type repeats and the C-terminus contains higly reserved sequences. The extreme C terminus is known to be essential for the phosphorylation of eukaryotic elongation factor-2 (eEF2). 


Ubiquitosly expressed in nomal tissues. Activity is increased in some tumors.




EEF2K protein belongs to alfa-kinases family of protein kinases. Its activity is dependent to Ca2+/calmodulin kinase and phosphorilates eukaryotic elongation factor-2 (eEF2) at Thr56 and inhibits it association/binding with ribosomes, thus regulates the elongation phase of translation.



No mutations identified other than SNPs repsesenting normal variations (

Implicated in

Entity name
Breast Cancer
eEF-2K protein expression promotes in breast cancer cell survival, invasion, migration and tumorigenesis (Tekedereli et al., 2012). eEF-2k highly expressed lines compared with normal non-tumorigenic breast epithelium and ist expression is associated with poor patient survival and prognosis (Meric-Bernstam et al., 2012).
Overexpression of eEF-2k is associated with shorter survival and poor prognosis (outcome) in Estrogen receptor (ER) positive (Tekedereli et al., 2012) and triple negative or ER (-) breast cancer patients (Ozpolat et al in press).
Entity name
Pancreatic cancer
eEF-2K protein is significantly overexpressed in pancreatic cancer cell lines and its inhibition lead to inhibition of cell proliferation, in invasion and migration and induces apoptosis (Ashour et al., 2014a; Ashour et al., 2014b).
Entity name
Glioblastome multiforme (GBM)
): eEF-2K protects cells from nutrient deprivation and in conferring tumor cell adaptation to nutrient deprivation and metabolic stress by blocking translation elongation (Bowden et al., 2013).
Entity name
Azheimer disease (AD)
Levels of p-eEF2K were found to be significantly increased, and total eEF2 significantly decreased in AD, when compared to controls in the brain tissue. levels of p-MTOR (Ser2481), and EIF4EBP1 (p-4E-BP1) (Thr70 and Ser65) dramatically increase in AD, and are positively significantly correlated with total tau and p-tau proteins.
Entity name
eEF2K protein increases in mesenteric artery from spontaneously hypertensive rats (SHR). eEF2K mediates TNF-?-induced vascular inflammation via ROS-dependent mechanism, which is at least partly responsible for the development of hypertension in SHR (Usui et al., 2013).


Pubmed IDLast YearTitleAuthors
216056782011Purification and characterization of tagless recombinant human elongation factor 2 kinase (eEF-2K) expressed in Escherichia coli.Abramczyk O et al
252159322014Elongation factor-2 kinase regulates TG2/β1 integrin/Src/uPAR pathway and epithelial-mesenchymal transition mediating pancreatic cancer cells invasion.Ashour AA et al
147095572004Stimulation 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.Browne GJ et al
23909901990Functional properties of phosphorylated elongation factor 2.Carlberg U et al
62627881981Regulation of intracellular levels of calmodulin and tubulin in normal and transformed cells.Chafouleas JG et al
41939161970[Nissl staining with cresyl violet].Krutsay M et al
237067432013The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.Leprivier G et al
231023762012Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer.Meric-Bernstam F et al
85147781993Purification and characterization of calmodulin-dependent protein kinase III from rabbit reticulocytes and rat pancreas.Mitsui K et al
39066541985Identification of calmodulin-dependent protein kinase III and its major Mr 100,000 substrate in mammalian tissues.Nairn AC et al
83289701993Cyclic AMP-dependent protein kinase phosphorylates rabbit reticulocyte elongation factor-2 kinase and induces calcium-independent activity.Redpath NT et al
35695281987Ca2+/calmodulin-dependent phosphorylation of elongation factor 2.Ryazanov AG et al
33867561988Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation.Ryazanov AG et al
223298312012Calcium/calmodulin stimulates the autophosphorylation of elongation factor 2 kinase on Thr-348 and Ser-500 to regulate its activity and calcium dependence.Tavares CD et al
229117542012Targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer.Tekedereli I et al
238123892013Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation.Usui T et al

Other Information

Locus ID:

NCBI: 29904
MIM: 606968
HGNC: 24615
Ensembl: ENSG00000103319


dbSNP: 29904
ClinVar: 29904
TCGA: ENSG00000103319


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Oxytocin signaling pathwayKEGGhsa04921
Oxytocin signaling pathwayKEGGko04921
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
Signal TransductionREACTOMER-HSA-162582
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
PI3K CascadeREACTOMER-HSA-109704
PKB-mediated eventsREACTOMER-HSA-109703
mTOR signallingREACTOMER-HSA-165159
mTORC1-mediated signallingREACTOMER-HSA-166208
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
237067432013The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.133
147095572004Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398.107
160982022005Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain.97
150240862004A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin.95
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
203005202010Cytoprotective effect of the elongation factor-2 kinase-mediated autophagy in breast cancer cells subjected to growth factor inhibition.37
183377512008cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner.36
253307702014Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.35
121716002002Stress-induced regulation of eukaryotic elongation factor 2 kinase by SB 203580-sensitive and -insensitive pathways.34
229117542012Targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer.33


Bulent Ozpolat ; Ozgur Ozkayar

EEF2K (eukaryotic elongation factor 2 kinase)

Atlas Genet Cytogenet Oncol Haematol. 2016-01-01

Online version: