Contents

EEF2K

Protein-coding gene in humans

EEF2K
Identifiers
Aliases	EEF2K, HSU93850, eEF-2K, eukaryotic elongation factor 2 kinase, CAMKIII, calmodulin-dependent protein kinase III
External IDs	OMIM: 606968; MGI: 1195261; HomoloGene: 7299; GeneCards: EEF2K; OMA:EEF2K - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p12.2 Start 22,206,278 bp[1] End 22,288,738 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F2 Start 120,442,054 bp[2] End 120,506,673 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of leg sural nerve skin of abdomen muscle of thigh cerebellum cerebellar cortex cerebellar hemisphere skeletal muscle tissue right hemisphere of cerebellum gastric mucosa Top expressed in ascending aorta primary oocyte aortic valve secondary oocyte zygote seminal vesicula urothelium urinary bladder transitional epithelium of urinary bladder medullary collecting duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding calcium ion binding protein kinase activity transferase activity protein serine/threonine kinase activity kinase activity translation factor activity, RNA binding calmodulin binding ATP binding elongation factor-2 kinase activity Cellular component cytoplasm cytosol postsynaptic density dendritic spine Biological process positive regulation of endocytosis cellular response to cAMP response to ischemia negative regulation of apoptotic process cellular response to insulin stimulus positive regulation of synapse assembly translational elongation cellular response to calcium ion protein autophosphorylation cellular response to brain-derived neurotrophic factor stimulus cellular response to anoxia protein phosphorylation positive regulation of dendritic spine morphogenesis regulation of protein autophosphorylation response to prolactin phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 29904 13631 Ensembl ENSG00000103319 ENSG00000284161 ENSMUSG00000035064 UniProt O00418 O08796 RefSeq (mRNA) NM_013302 NM_001267710 NM_001267711 NM_007908 RefSeq (protein) NP_037434 NP_001254639 NP_001254640 NP_031934 Location (UCSC) Chr 16: 22.21 – 22.29 Mb Chr 7: 120.44 – 120.51 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Eukaryotic elongation factor-2 kinase (eEF-2 kinaseoreEF-2K), also known as calmodulin-dependent protein kinase III (CAMKIII) and calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase,^[5] is an enzyme that in humans is encoded by the EEF2K gene.^[6][7]

Function[edit]

eEF-2 kinase is a highly conserved protein kinase in the calmodulin-mediated signaling pathway that links multiple up-stream signals to the regulation of protein synthesis. It phosphorylates eukaryotic elongation factor 2 (EEF2) and thus inhibits the EEF2 function.^[6][8]

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.^[9][10] 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.^[10]

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.^[9]

Clinical significance[edit]

The activity of this kinase is increased in many cancers and may be a valid target for anti-cancer treatment.^[6][11]

It is also suggested that eEF-2K may play a role the rapid anti-depressant effects of ketamine through its regulation of neuronal protein synthesis.^[12]

Cancer[edit]

eEF-2K expression is often upregulated in cancer cells, including breast and pancreatic cancers and promotes cell proliferation, survival, motility/migration, invasion and tumorigenesis.^[13][14]

References[edit]

Further reading[edit]