Information on EC 2.7.11.26 - tau-protein kinase and Organism(s) Mus musculus and UniProt Accession Q9WV60

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Mus musculus
UNIPROT: Q9WV60


The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.26
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RECOMMENDED NAME
GeneOntology No.
tau-protein kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:[tau-protein] O-phosphotransferase
Activated by tubulin. Involved in the formation of paired helical filaments, which are the main fibrous component of all fibrillary lesions in brain and are associated with Alzheimer's disease.
CAS REGISTRY NUMBER
COMMENTARY hide
111694-09-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
stimulation of GSK-3beta both in vitro and in vivo induces tau hyperphosphorylation with impairments of the cognitive functions, whereas inhibition of GSK-3beta improves tau pathologies and memory deficits. Stimulation of EphB2 upregulates PI3K and Akt with inhibition of GSK-3beta. Stimulation of EphB2 attenuates tau phosphorylation both in vitro and in hippocampus of human tau transgenic mice
evolution
TTBK2 is a serine/threonine protein kinase of the CK1 superfamily
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + protein tau
ADP + protein tau phosphate
show the reaction diagram
the antagonist of GSK-3beta in protein tau phosphorylation is the phosphatase PP2A
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-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
ATP + beta-catenin
ADP + phosphorylated beta-catenin
show the reaction diagram
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
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substrate of isoform GSK-3alpha
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-
?
ATP + CEP164
ADP + phospho-CEP164
show the reaction diagram
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-
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?
ATP + CEP97
ADP + phospho-CEP97
show the reaction diagram
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-
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?
ATP + eIF2B peptide
ADP + phosphorylated eIF2B peptide
show the reaction diagram
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-
-
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?
ATP + histone H1
ADP + histone H1 phosphate
show the reaction diagram
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Cdk5 substrate
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ATP + phospho-glycogen synthase peptide-2
ADP + phosphorylated phospho-glycogen synthase peptide-2
show the reaction diagram
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GSK3 substrate
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-
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ATP + protein tau
ADP + protein tau phosphate
show the reaction diagram
ATP + TDP-43
ADP + phospho-TDP-43
show the reaction diagram
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-
-
?
ATP + tubulin
ADP + phospho-tubulin
show the reaction diagram
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-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
ATP + protein tau
ADP + protein tau phosphate
show the reaction diagram
ATP + tubulin
ADP + phospho-tubulin
show the reaction diagram
Q3UVR3
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-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
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required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
lithium chloride
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15 mM
(2'Z,3'E)-6-bromoindirubin-3'-oxime
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2-cyanoethyl alsterpaullone
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4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione
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6-bromo-indirubin-3'-oxime
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6-bromoindirubin-3'-oxim
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6-bromoindirubin-3'-oxime
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alsterpaullone
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AR-A014418
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selective ATP-competitive inhibitor of GSK3
compound C
inhibits tau protein phosphorylation by AMPK
CT99021
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kenpaullone
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p25
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p25 overexpressing mice have reduced GSK3beta activity
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roscovitine
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Cdk5 inhibitor
SB 216763
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SB-216763
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selective ATP-competitive inhibitor of GSK3
SB-415286
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trans-activating transcriptor-eIF2B
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acts as a competitive inhibitor of GSK-3
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
AMP
AMP-activated protein kinase
cisplatin
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GSK-3 is activated by cisplatin treatment of HEI-OC1 cells, 0.02 mM cisplatin induces phosphorylation of Tyr216 GSK-3beta in HEI-OC1 cells but reduces the phosphorylation of Ser9 GSK-3beta, the activity of GSK-3beta is regulated negatively by the phosphorylation of Ser9 and positively by the phosphorylation of Tyr216
CP-681301
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CP-681301 treatment reverses the inhibition of GSK3beta activity
ether
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dramatic increase in the phosphorylation level of Ser9 of TPKI/GSK3beta immediately and 10 min after ether administration, followed by rapid virtual reversion to baseline by 20 min, no significant changes in the protein level or Tyr216 phosphorylation level of the enzyme
GF-109203X
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metformin
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p25
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cyclin activator, dependent on, over 10fold increase in activity of CDK5
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p35
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tightly bound neuronal activator of cdk5, required for activity with regulatory function, p39 activates to a greater extent compared to p35 in vitro
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p39
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tightly bound neuronal activator of cdk5, required for activity with regulatory function, p39 activates to a greater extent compared to p35 in vitro, p39 is the activator activator in vivo
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soluble beta-amyloid oligomers
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activate GSK-3beta mediated tau phosphorylation and increase toxicity, reduced content of soluble, not insoluble, amyloid oligomers reduces the tau phosphorylation activity, specific antibodies can inhibit the activation, overview
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Wortmannin
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additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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assay at
7.5
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the active form of GSK-3beta is co-localized with the neurofibrillary tangles in the Alzheimer disease brains
Manually annotated by BRENDA team
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entire amygdala or ventroposterior quadrant of cerebral hemisphere
Manually annotated by BRENDA team
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immortilized embryonic brain cortex cell line
Manually annotated by BRENDA team
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immortilized embryonic brain cortex cell line overexpressing the human tau protein
Manually annotated by BRENDA team
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bone marrow-derived mesenchymal stem cell
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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mainly
Manually annotated by BRENDA team
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GSK-3beta partially localizes within mitochondria
Manually annotated by BRENDA team
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isoform GSK-3alpha
Manually annotated by BRENDA team
additional information
PDB
SCOP
CATH
UNIPROT
ORGANISM
Mus musculus;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
calculated from cDNA sequence
47000
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SDS-PAGE
100000
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immunoprecipitation, lysosomal degradation product of full-length TTBK1
additional information
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absence of a 230-kDa protein in the mouse cortex, suggests a very small quantity of full-length TTBK1
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
alternative splicing isoform of tau protein kinase I/glycogen synthase kinase 3beta, by RT-PCR also found in rat and human brains, transient expression in COS-7 cells
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His-tagged GSK3beta expressed in Escherichia coli BL21, into pEGFP vector and N18 cells transiently transfected
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mouse TTK cDNA isolated using amino acid sequences of purified bovine brain TTK
p25-induced Cdk5 over-activation of Cdk5 in young and old transgenic mice
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
5-azacytidine treatment (0.005 mM for 24 h) causes significant up-regulation of GSK-3beta whereas it stimulates GSK-3alpha expression only modestly
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GSK-3beta levels are elevated by about 80% in APP transgenic neuronal cultures
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LiCl and BIO also reduce the expression of GSK3beta
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treatment of hippocampal cells with 3-nitropropionic acid (0.5 mM) modifies GSK-3beta levels shown by an increase in proteolysis and a decrease of Ser-9 phosphorylation
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information
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phosphorylation of T231 by GSK3beta may play an important role in tauís hyperphosphorylation and functional regulation