Summary

Name GSK3A
Full Name Glycogen synthase kinase-3 alpha
Synonyms GSK-3 alpha, Serine/threonine-protein kinase GSK3A, 2.7.11.1
Primary ID P49840
Links - -
Type protein
Relations 71
Pathways Alzheimer
Inhibitors SB 415286; CHIR 99021; CHIR-98014
Function Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1 (PubMed:11749387, PubMed:17478001, PubMed:19366350). Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350). Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates activity img/direct_inhibition.png phosphorylation ANKRD28 0.2
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation CAMKK2 0.272
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation LRP6 0.618
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MCL1 0.468
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.624
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.295
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.331
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.353
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.334
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.328
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3A 0.362
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3A 0.267
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.349
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.38
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation JUN 0.335
Publications: 4 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation FCAR 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation GPSM3 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GRB14 0.267
Publications: 3 Organism: In Vitro
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation GATA6 0.268
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MITF 0.297
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MAFA 0.2
Publications: 4 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAFA 0.2
Publications: 4 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation EIF2B5 0.376
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.439
Publications: 2 Organism: Homo Sapiens
Pathways:Alzheimer
+ up-regulates activity img/direct-activation.png phosphorylation STMN3 0.253
Publications: 1 Organism: In Vitro
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation UNG 0.2
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GYS1 0.418
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPT 0.439
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer
+ img/unknown.png phosphorylation PKD2 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ up-regulates activity img/direct-activation.png phosphorylation NIFK 0.2
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation RELA 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation AKT1 0.624
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation AKT 0.625
Publications: 1 Organism: Mus Musculus
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MYC 0.415
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation NBR1 0.329
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation SFPQ 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ARHGAP31 0.341
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation GSK3A 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer
+ down-regulates img/direct_inhibition.png chemical inhibition GSK3A 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation OSBP2 0.2
Publications: 1
+ up-regulates img/direct-activation.png phosphorylation TSC2 0.367
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NOTCH1 0.324
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png GSK3A 0.419
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer
+ up-regulates img/direct-activation.png phosphorylation MAFB 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAF 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png cleavage GSK3A 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer
+ down-regulates img/direct_inhibition.png phosphorylation MAFB 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition GSK3A 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png cleavage GSK3A 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition GSK3A 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png cleavage GSK3A 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.54
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAF 0.2
Publications: 1 Organism: Homo Sapiens