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Literature summary for 2.7.11.26 extracted from
- Glycogen synthase kinase-3beta2 has lower phosphorylation activity to tau than glycogen synthase kinase-3beta1 (2011), Biol. Pharm. Bull., 34, 146-149.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| GSK-3beta consists of two splice variants, the major short form (GSK-3beta1) and the minor long form (GSK-3beta2), whose structural difference is the insert of only 13 amino acid residues to the C-terminal side of the catalytic site of GSK-3beta1, recombinant expression of isozymes GSK-3beta1 and GSK-3beta2 in HEK-293T cells | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| microtubule | - |
Homo sapiens | 5874 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens |  |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [amyloid precursor protein] | Homo sapiens | phosphorylation of the intracellular domain Thr668 of APP by GSK-3beta | ADP + O-phospho-[amyloid precursor protein] | - |
? | |
| ATP + [tau-protein] | Homo sapiens | - |
ADP + O-phospho-[tau-protein] | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P49841 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Homo sapiens | - |
| central nervous system | splicing variant GSK-3beta2 | Homo sapiens | - |
| additional information | GSK-3beta consists of two splice variants, the major short form GSK-3beta1 that is distributed in many organs, and the minor long form GSK-3beta2, which is present in central nervous system | Homo sapiens | - |
| neuron | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [amyloid precursor protein] | phosphorylation of the intracellular domain Thr668 of APP by GSK-3beta | Homo sapiens | ADP + O-phospho-[amyloid precursor protein] | - |
? | |
| ATP + [tau-protein] | - |
Homo sapiens | ADP + O-phospho-[tau-protein] | - |
? | |
| additional information | recombinant splicing variant GSK-3beta2 has lower phosphorylation activity to tau than splicing variant GSK-3beta1 in vitro, although the phosphorylation activities of the two variants to a synthetic peptide substrate pGS-2 are comparable | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| glycogen synthase kinase-3beta1 | - |
Homo sapiens |
| glycogen synthase kinase-3beta2 | - |
Homo sapiens |
| GSK-3beta1 | - |
Homo sapiens |
| GSK-3beta2 | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 30 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.2 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | the deletion of the C-terminal tail of slicing variant GSK-3beta2 results in considerable reduction of tau phosphorylation activity as compared with GSK-3beta1 | Homo sapiens |
| additional information | glycogen synthase kinase-3beta2 has lower phosphorylation activity to tau than glycogen synthase kinase-3beta1. The lower tau phosphorylation activity of GSK-3beta2 is due to the weak interaction of its C-terminal tail with tau | Homo sapiens |
| physiological function | glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase that phosphorylate protein substrates involved in Alzheimer's disease (AD), such as microtubule-associated protein tau and amyloid precursor protein (APP). Splicing variant GSK-3beta2 has lower phosphorylation activity to tau at Alzheimer disease-relevant epitope Ser396 than GSK-3b 1 in cells, whereas the two variants exhibit equivalent levels of phosphorylation activities to amyloid precursor protein. Tau is an unfavorable substrate of GSK-3beta2. Changes in the balance of GSK-3beta2/-3beta1 in neurons underlie tau hyperphosphorylation in Alzheimer's disease. The intracellular domain Thr668 of APP is phosphorylated by GSK-3beta, the phosphorylation regulates APP function and metabolism | Homo sapiens |
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