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Literature summary for 2.7.11.17 extracted from
- Nitric oxide induces Ca2+-independent activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) (2014), J. Biol. Chem., 289, 19458-19465.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | each kinase subunit is activated separately by direct binding of Ca2+/CaM, which can also induce intra-holoenzyme inter-subunit Thr286 autophosphorylation. NO induces S-nitrosylation at Cys280/289 which directly generates autonomous activity of CaMKIIalpha, but simultaneous nitrosylation at both sites is required. The kinase is first phosphorylated at Thr286 on ice, phosphorylation is stopped by addition of EDTA, then the kinase is reacted with NO at room temperature. Thr305/306 phosphorylation is induced by chelating Ca2+ in the presence of ATP (after Thr286 phosphorylation or nitrosylation) | Rattus norvegicus |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of GST-tagged CaMKIIalpha in HEK-293 cells | Rattus norvegicus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| T286A | site-directed mutagenesis | Rattus norvegicus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| EDTA | - |
Rattus norvegicus |  |
| NO | a reduction of CaMKII activity by S-nitrosylation at Cys6 is observed, but only after prolonged exposure of over 5 min to NO donors | Rattus norvegicus | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | each kinase subunit is activated separately by direct binding of Ca2+/CaM, which can also induce intra-holoenzyme inter-subunit Thr286 autophosphorylation | Rattus norvegicus | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Rattus norvegicus | P08413 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | direct binding of Ca2+ and calmodulin to each of the 12 subunits induces intra-holoenzyme inter-subunit Thr286 autophosphorylation | Rattus norvegicus |
| S-nitrosylation | NO induces S-nitrosylation at Cys280/289 which directly generates autonomous activity of CaMKIIalpha, but simultaneous nitrosylation at both sites is required. And a reduction of CaMKIIalpha activity by S-nitrosylation at Cys6 is also observed, but only after prolonged exposure of over 5 min to NO donors | Rattus norvegicus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | CaMKII is the main isozyme in the brain | Rattus norvegicus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + syntide-2 | a peptide substrate | Rattus norvegicus | ADP + phosphorylated syntide-2 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dodecamer | CaMKII forms 12meric holoenzymes via C-terminal association domains, with the kinase domains radiating outward | Rattus norvegicus |
| More | structure of the CaMKII kinase and regulatory domains, in the basal inactive state, the substrate binding S-site is blocked by the regulatory domain, which is held in place in part by interactions with the neighboring T-site | Rattus norvegicus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Ca2+/calmodulin-dependent protein kinase IIalpha | - |
Rattus norvegicus |
| Ca2+/CaM-dependent protein kinase IIalpha | - |
Rattus norvegicus |
| CaMKIIalpha | - |
Rattus norvegicus |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| Calmodulin | each kinase subunit is activated separately by direct binding of Ca2+/CaM, which can also induce intra-holoenzyme inter-subunit Thr286 autophosphorylation | Rattus norvegicus | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Rattus norvegicus | nitric oxide induces Ca2+-independent activity of Ca2+/calmodulin-dependent protein kinase II | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | CaMKIIalpha inhibition protects from NO-induced neuronal cell death. Isozyme mutation of either site, Cys280 or Cys289, abolishes autonomous Ca2+-independent activity of the isozyme | Rattus norvegicus |
| metabolism | both signaling by nitric oxide (NO) and by isozyme CaMKIIalpha are implicated in two opposing forms of synaptic plasticity underlying learning and memory, as well as in excitotoxic/ischemic neuronal cell death | Rattus norvegicus |
| physiological function | isozyme Ca2+/calmodulin-dependent protein kinase IIalpha mediates both long-term potentiation and depression of synaptic strength, as well as excitotoxic neuronal cell death during ischemia, regulation of CaMKII by another second messenger system. For CaMKIIalpha, these functions specifically involve also Ca2+-independent autonomous activity, traditionally generated by Thr286 autophosphorylation. NO-induced S-nitrosylation of CaMKIIalpha also directly generates autonomous activity | Rattus norvegicus |
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