UniProt functional annotation for O00418



	UniProt functional annotation for O00418

UniProt code: O00418.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:9144159}.

Catalytic activity: 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};

Activity regulation: Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent. {ECO:0000250}.

Biophysicochemical properties: Kinetic parameters: KM=1.2 uM for EEF2 {ECO:0000269|PubMed:11015200}; Vmax=4 nmol/min/mg enzyme {ECO:0000269|PubMed:11015200};

Subunit: Monomer or homodimer (Probable). Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (PubMed:11015200). {ECO:0000269|PubMed:11015200, ECO:0000305}.

Ptm: 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. {ECO:0000269|PubMed:11015200, ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:18337751, ECO:0000269|PubMed:21112387, ECO:0000269|PubMed:22216903}.

Similarity: Belongs to the protein kinase superfamily. Alpha-type protein kinase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:14709557, ECO:0000269\|PubMed:9144159}.


Catalytic activity:		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};
Activity regulation:		Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent. {ECO:0000250}.
Biophysicochemical properties:		Kinetic parameters: KM=1.2 uM for EEF2 {ECO:0000269\|PubMed:11015200}; Vmax=4 nmol/min/mg enzyme {ECO:0000269\|PubMed:11015200};
Subunit:		Monomer or homodimer (Probable). Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (PubMed:11015200). {ECO:0000269\|PubMed:11015200, ECO:0000305}.
Ptm:		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. {ECO:0000269\|PubMed:11015200, ECO:0000269\|PubMed:11500363, ECO:0000269\|PubMed:11500364, ECO:0000269\|PubMed:14709557, ECO:0000269\|PubMed:18337751, ECO:0000269\|PubMed:21112387, ECO:0000269\|PubMed:22216903}.
Similarity:		Belongs to the protein kinase superfamily. Alpha-type protein kinase family. {ECO:0000305}.