EEF2K

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Eukaryotic elongation factor-2 kinase
Identifiers
Symbols EEF2K ; HSU93850; eEF-2K
External IDs OMIM606968 MGI1195261 HomoloGene7299 ChEMBL: 5026 GeneCards: EEF2K Gene
EC number 2.7.11.20
RNA expression pattern
PBB GE EEF2K gnf1h00131 at tn.png
PBB GE EEF2K gnf1h00132 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 29904 13631
Ensembl ENSG00000103319 ENSMUSG00000035064
UniProt O00418 O08796
RefSeq (mRNA) NM_013302 NM_001267710
RefSeq (protein) NP_037434 NP_001254639
Location (UCSC) Chr 16:
22.22 – 22.3 Mb
Chr 7:
120.84 – 120.91 Mb
PubMed search [1] [2]

Eukaryotic elongation factor-2 kinase (eEF-2 kinase or eEF-2K), also known as calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase (CaMKIII) is an enzyme that in humans is encoded by the EEF2K gene.[1][2]

Function[edit]

eEF-2 kinase is 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.[1]

Activation[edit]

The activity of eEF-2K is dependent on calcium and calmodulin. Activation of eEF-2K proceeds by a sequential two-step mechanism. First, calcium-calmodulin binds with high affinity to activate the kinase domain, triggering rapid autophosphorylation of Thr-348.[3][4] In the second step, autophosphorylation of Thr-348 leads to a conformational change in the kinase likely supported by the binding of phospho-Thr-348 to an allosteric phosphate binding pocket in the kinase domain. This increases the activity of eEF-2K against its substrate, elongation factor 2.[4]

eEF-2K can gain calcium-independent activity through autophosphorylation of Ser-500. However, calmodulin must remain bound to the enzyme for its activity to be sustained.[3]

Clinical significance[edit]

The activity of this kinase is increased in many cancers and may be a valid target for anti-cancer treatment.[1][5]

References[edit]

  1. ^ a b c "Entrez Gene: EEF2K eukaryotic elongation factor-2 kinase". 
  2. ^ Ryazanov AG, Ward MD, Mendola CE, Pavur KS, Dorovkov MV, Wiedmann M, Erdjument-Bromage H, Tempst P, Parmer TG, Prostko CR, Germino FJ, Hait WN (May 1997). "Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 4884–9. doi:10.1073/pnas.94.10.4884. PMC 24600. PMID 9144159. 
  3. ^ a b Tavares CD, O'Brien JP, Abramczyk O, Devkota AK, Shores KS, Ferguson SB, Kaoud TS, Warthaka M, Marshall KD, Keller KM, Zhang Y, Brodbelt JS, Ozpolat B, Dalby KN (2012 Mar 20). "Calcium/calmodulin stimulates the autophosphorylation of elongation factor 2 kinase on Thr-348 and Ser-500 to regulate its activity and calcium dependence.". Biochemistry 51 (11): 2232–45. PMID 22329831. 
  4. ^ a b Tavares CD, Ferguson SB, Giles DH, Wang Q, Wellmann RM, O'Brien JP, Warthaka M, Brodbelt JS, Ren P, Dalby KN (2014 Aug 22). "The molecular mechanism of eukaryotic elongation factor 2 kinase activation.". The Journal of biological chemistry 289 (34): 23901–16. PMID 25012662. 
  5. ^ Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, Agnihotri S, El-Naggar A, Yu B, Somasekharan SP, Faubert B, Bridon G, Tognon CE, Mathers J, Thomas R, Li A, Barokas A, Kwok B, Bowden M, Smith S, Wu X, Korshunov A, Hielscher T, Northcott PA, Galpin JD, Ahern CA, Wang Y, McCabe MG, Collins VP, Jones RG, Pollak M, Delattre O, Gleave ME, Jan E, Pfister SM, Proud CG, Derry WB, Taylor MD, Sorensen PH (May 2013). "The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation". Cell 153 (5): 1064–79. doi:10.1016/j.cell.2013.04.055. PMID 23706743. 

Further reading[edit]