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Literature summary for 2.7.11.20 extracted from
- Elongation factor 2 kinase is regulated by proline hydroxylation and protects cells during hypoxia (2015), Mol. Cell. Biol., 35, 1788-1804.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| Calmodulin | required, enzyme eEF2K interacts with calmodulin (CaM) through a binding site which lies almost immediately N terminal to its catalytic domain. Comparison of human and murine CaM-binding sites, overview. Hydroxylation of Pro98 impairs binding of eEF2K to calmodulin and its activation by calmodulin | Homo sapiens |  |
| Calmodulin | required, enzyme eEF2K interacts with calmodulin (CaM) through a binding site which lies almost immediately N terminal to its catalytic domain. Comparison of human and murine CaM-binding sites, overview. Hydroxylation of Pro98 impairs binding of eEF2K to calmodulin and its activation by calmodulin | Mus musculus | |
| additional information | AMPK activates eEF2K via phosphorylation, which is not involved in enzyme activation in hypoxia conditions. Hypoxia or DMOG treatment enhance eEF2 phosphorylation without increasing the levels of the eEF2K protein. | Homo sapiens | |
| additional information | AMPK activates eEF2K via phosphorylation, which is not involved in enzyme activation in hypoxia conditions. Hypoxia or DMOG treatment enhance eEF2 phosphorylation without increasing the levels of the eEF2K protein. | Mus musculus |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant overexpression of FLAG-tagged enzyme from pcDNA3.1 vector in HEK-293 cells, recombinant expression of GST-tagged wild-type and mutant eEF2K enzymes in Escherichia coli strain Rosetta(DE3)pLysS | Homo sapiens |
| recombinant overexpression of FLAG-tagged enzyme from pcDNA3.1 vector in HEK-293 cells, recombinant expression of GST-tagged wild-type and mutant eEF2K enzymes in Escherichia coli strain Rosetta(DE3)pLysS | Mus musculus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| D97A | site-directed mutagenesis | Homo sapiens |
| D97A | site-directed mutagenesis | Mus musculus |
| P96A | site-directed mutagenesis | Mus musculus |
| P98A | site-directed mutagenesis | Homo sapiens |
| W99A | site-directed mutagenesis | Homo sapiens |
| W99A | site-directed mutagenesis | Mus musculus |
| W99L | site-directed mutagenesis | Homo sapiens |
| W99L | site-directed mutagenesis | Mus musculus |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | required for maintaining the interaction with activator calmodulin | Homo sapiens | |
| Ca2+ | required for maintaining the interaction with activator calmodulin | Mus musculus | |
| Mg2+ | required | Homo sapiens | |
| Mg2+ | required | Mus musculus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [elongation factor 2] | Homo sapiens | - |
ADP + [elongation factor 2] phosphate | - |
? | |
| ATP + [elongation factor 2] | Mus musculus | - |
ADP + [elongation factor 2] phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O00418 | - |
- |
| Mus musculus | O08796 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | AMPK activates eEF2K via phosphorylation. Inhibition of proline hydroxylases, e.g. by DMOG, induces the phosphorylation of eEF2 independently of altered mTORC1 or AMPK signaling | Homo sapiens |
| phosphoprotein | AMPK activates eEF2K via phosphorylation. Inhibition of proline hydroxylases, e.g. by DMOG, induces the phosphorylation of eEF2 independently of altered mTORC1 or AMPK signaling | Mus musculus |
| side-chain modification | eEF2K is subject to hydroxylation on proline 98 catalyzed by proline hydroxylases | Mus musculus |
| side-chain modification | eEF2K is subject to hydroxylation on proline 98 catalyzed by proline hydroxylases. Hydroxylation of Pro98 impairs binding of eEF2K to calmodulin and its activation by calmodulin | Homo sapiens |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant GST-tagged wild-type and mutant eEF2K enzymes from Escherichia coli strain Rosetta(DE3)pLysS | Homo sapiens |
| recombinant GST-tagged wild-type and mutant eEF2K enzymes from Escherichia coli strain Rosetta(DE3)pLysS | Mus musculus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| fibroblast | mouse embryonic fibroblasts, MEFs | Mus musculus | - |
| HCT-116 cell | - |
Homo sapiens | - |
| neuron | primary cultured cortical neurons | Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + MH-1 peptide | - |
Homo sapiens | ADP + phosphorylated MH-1 peptide | - |
? | |
| ATP + MH-1 peptide | - |
Mus musculus | ADP + phosphorylated MH-1 peptide | - |
? | |
| ATP + [elongation factor 2] | - |
Homo sapiens | ADP + [elongation factor 2] phosphate | - |
? | |
| ATP + [elongation factor 2] | - |
Mus musculus | ADP + [elongation factor 2] phosphate | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| eEF2 kinase | - |
Homo sapiens |
| eEF2 kinase | - |
Mus musculus |
| eEF2K | - |
Homo sapiens |
| eEF2K | - |
Mus musculus |
| elongation factor 2 kinase | - |
Homo sapiens |
| elongation factor 2 kinase | - |
Mus musculus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Homo sapiens |
| 30 | - |
assay at | Mus musculus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7 | - |
assay at | Homo sapiens |
| 7 | - |
assay at | Mus musculus |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | the expression of the mRNA for EEF2K is probably regulated in multiple ways, e.g. downstream of AMPK, and in some settings by mTORC1 signaling and HIF1 | additional information |
| Mus musculus | the expression of the mRNA for EEF2K is probably regulated in multiple ways, e.g. downstream of AMPK, and in some settings by mTORC1 signaling and HIF1 | additional information |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | transcription elongation is controlled by phosphorylation of eukaryotic elongation factor 2 (eEF2), which inhibits its activity and is catalyzed by eEF2 kinase (eEF2K), a calcium/calmodulin-dependent alpha-kinase. eEF2K activity is regulated through several signaling pathways linked, e.g., to nutrient availability. Hypoxia causes the activation of eEF2K and induces eEF2 phosphorylation. eEF2K is subject to hydroxylation on proline 96. Proline hydroxylation is catalyzed by proline hydroxylases, oxygen-dependent enzymes which are inactivated during hypoxia. Hypoxia-induced eEF2 phosphorylation requires eEF2K and is not catalyzed by AMPK, it does also not require signaling via AMPK or mTORC1. Pharmacological inhibition of proline hydroxylases, e.g. by DMOG treatment, also stimulates eEF2 phosphorylation. Pro96 lies in a universally conserved linker between the calmodulin-binding and catalytic domains of eEF2K. Its hydroxylation partially impairs the binding of calmodulin to eEF2K and markedly limits the calmodulin-stimulated activity of eEF2K. Neuronal cells depend on oxygen, and eEF2K helps to protect them from hypoxia. eEF2K is cytoprotective during hypoxia and other conditions of nutrient insufficiency, it aids the survival of neuronal cells during hypoxia and has a key role in helping cells withstand nutrient deficiency | Mus musculus |
| physiological function | transcription elongation is controlled by phosphorylation of eukaryotic elongation factor 2 (eEF2), which inhibits its activity and is catalyzed by eEF2 kinase (eEF2K), a calcium/calmodulin-dependent alpha-kinase. eEF2K activity is regulated through several signaling pathways linked, e.g., to nutrient availability. Hypoxia causes the activation of eEF2K and induces eEF2 phosphorylation. eEF2K is subject to hydroxylation on proline 98. Proline hydroxylation is catalyzed by proline hydroxylases, oxygen-dependent enzymes which are inactivated during hypoxia. Hypoxia-induced eEF2 phosphorylation requires eEF2K and is not catalyzed by AMPK, it does also not require signaling via AMPK or mTORC1. Pharmacological inhibition of proline hydroxylases, e.g. by DMOG treatment, also stimulates eEF2 phosphorylation. Pro98 lies in a universally conserved linker between the calmodulin-binding and catalytic domains of eEF2K. Its hydroxylation partially impairs the binding of calmodulin to eEF2K and markedly limits the calmodulin-stimulated activity of eEF2K. Neuronal cells depend on oxygen, and eEF2K helps to protect them from hypoxia. eEF2K is cytoprotective during hypoxia and other conditions of nutrient insufficiency, it aids the survival of neuronal cells during hypoxia and has a key role in helping cells withstand nutrient deficiency | Homo sapiens |
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