Summary

Name GSK3B
Full Name Glycogen synthase kinase-3 beta
Synonyms GSK-3 beta, Serine/threonine-protein kinase GSK3B, 2.7.11.1
Primary ID P49841
Links - -
Type protein
Relations 276
Pathways Hedgehog, Insulin Receptor, IGF and Myogenesis, Cell cycle: G1/S phase transition, Alzheimer Disease, Adipogenesis, MTOR Signaling
Inhibitors Indirubin; 601514-19-6; CHIR-98014; CHIR-99021
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), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png phosphorylation SNAI1 0.33
Publications: 14 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.09
Publications: 4 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CDKN1A 0.19
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition
+ up-regulates img/direct-activation.png phosphorylation FBXO4
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MUC1 0.08
Publications: 1
+ down-regulates img/direct_inhibition.png phosphorylation CAMKK2 0.27
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CREB1 0.36
Publications: 1 Organism: Rattus Norvegicus
Pathways:Adipogenesis
+ down-regulates img/direct_inhibition.png phosphorylation PHLPP1 0.25
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation LRP6 0.44
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation CABYR 0.17
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation BCL2L12 0.31
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MCL1 0.23
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation MCL1 0.23
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RCAN1 0.16
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation BAX 0.18
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer Disease
+ down-regulates img/direct_inhibition.png phosphorylation ARNTL 0.20
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RBM38 0.17
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation NOTCH2 0.41
Publications: 7 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CEBPB
Publications: 3 Organism: Homo Sapiens
Pathways:Adipogenesis
+ down-regulates activity img/direct_inhibition.png phosphorylation JUN 0.12
Publications: 3 Organism: Homo Sapiens, In Vitro
Pathways:Insulin Receptor
+ img/unknown.png phosphorylation CTNND1 0.40
Publications: 2 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation GPHN 0.37
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation BORA 0.17
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation CDX2 0.07
Publications: 4 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation HDAC4 0.24
Publications: 2 Organism: Homo Sapiens
Pathways:IGF and Myogenesis
+ down-regulates activity img/direct_inhibition.png phosphorylation HSF1 0.34
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation HSF1 0.34
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation KLF5 0.26
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis
+ down-regulates activity img/direct_inhibition.png phosphorylation CTNNB1 0.68
Publications: 11 Organism: Homo Sapiens
Tissue: Brain, Colonic Cancer Cell
+ up-regulates activity img/direct-activation.png phosphorylation TP53 0.07
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition
+ up-regulates img/direct-activation.png phosphorylation PRKCE 0.15
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PSEN1 0.34
Publications: 2 Organism: Homo Sapiens
Pathways:Alzheimer Disease
+ up-regulates img/direct-activation.png phosphorylation CIITA 0.09
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NFE2L1 0.28
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.25
Publications: 2 Organism: Homo Sapiens
Tissue: Brain
+ down-regulates img/direct_inhibition.png phosphorylation MAPT
Publications: 10 Organism: Homo Sapiens
Tissue: Brain
Pathways:Alzheimer Disease
+ img/unknown.png phosphorylation NR3C1 0.23
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis
+ up-regulates activity img/direct-activation.png phosphorylation DCX
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation SREBF1 0.27
Publications: 5 Organism: Homo Sapiens
Pathways:Insulin Receptor, MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation ACLY 0.51
Publications: 2
+ down-regulates activity img/direct_inhibition.png phosphorylation MYOCD 0.15
Publications: 8 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RELA 0.27
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation AXIN1 0.82
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAFA
Publications: 4 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAFA
Publications: 4 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NEFH 0.16
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPT 0.57
Publications: 13 Organism: Homo Sapiens
Pathways:Alzheimer Disease
+ down-regulates activity img/direct_inhibition.png phosphorylation DPYSL2 0.44
Publications: 2 Organism: Rattus Norvegicus
+ up-regulates img/direct-activation.png phosphorylation CRMP1 0.26
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation DPYSL3 0.28
Publications: 4 Organism: Rattus Norvegicus
+ down-regulates activity img/direct_inhibition.png phosphorylation EIF2B5 0.51
Publications: 2 Organism: In Vitro, Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation, binding EIF2B5 0.51
Publications: 2 Organism: Homo Sapiens
Tissue: Kidney
+ up-regulates img/direct-activation.png phosphorylation NR1D1 0.25
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SNCAIP 0.19
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GYS1 0.53
Publications: 8 Organism: Homo Sapiens, In Vitro,
Tissue: Muscle, Skeletal Muscle
Pathways:Insulin Receptor
+ down-regulates quantity by repression img/direct_inhibition.png phosphorylation CDC25A 0.33
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition
+ down-regulates img/direct_inhibition.png phosphorylation MNX1 0.03
Publications: 2 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation GLI2
Publications: 3 Organism: Homo Sapiens
Pathways:Hedgehog
+ down-regulates activity img/direct_inhibition.png phosphorylation HNRNPD 0.49
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation HNRNPD 0.49
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDH1 0.16
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation KAT5 0.30
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation ROR2 0.16
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B
Publications: 2 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, Insulin Receptor, MTOR Signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B 0.28
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png dephosphorylation GSK3B
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.33
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B 0.49
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B 0.35
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.50
Publications: 1 Organism: Homo Sapiens
Pathways:MTOR Signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B 0.59
Publications: 2 Organism: Homo Sapiens
Pathways:Adipogenesis, IGF and Myogenesis
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation GSK3B
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B 0.64
Publications: 1 Organism: Homo Sapiens
Pathways:Hedgehog
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.23
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.35
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.12
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation NFKB1 0.28
Publications: 2 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation SPAG5 0.41
Publications: 4 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HIST1H1B 0.30
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NACA 0.44
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CEBPA 0.21
Publications: 2 Organism: Mus Musculus
Pathways:Adipogenesis
+ up-regulates activity img/direct-activation.png phosphorylation CEBPB
Publications: 1 Organism: Mus Musculus
Pathways:Adipogenesis
+ down-regulates img/direct_inhibition.png phosphorylation CCND2 0.20
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CCND3 0.39
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CCND1 0.25
Publications: 2 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CCND1 0.25
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PTEN 0.19
Publications: 1 Organism: Homo Sapiens
Pathways:Insulin Receptor, MTOR Signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation EIF4EBP1 0.28
Publications: 3 Organism: Homo Sapiens
Tissue: Kidney
Pathways:Insulin Receptor, MTOR Signaling
+ down-regulates img/direct_inhibition.png phosphorylation CCNE1 0.33
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.24
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.37
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MYC 0.17
Publications: 3 Organism: Rattus Norvegicus, Homo Sapiens
Pathways:Cell cycle: G1/S phase transition
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation SMAD3 0.30
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis, Cell cycle: G1/S phase transition
+ down-regulates img/direct_inhibition.png phosphorylation SFPQ
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PPP1R2 0.45
Publications: 1 Organism: Bos Taurus
+ img/unknown.png phosphorylation APP 0.16
Publications: 1 Organism: In Vitro
Pathways:Alzheimer Disease
+ up-regulates activity img/direct-activation.png phosphorylation GSK3B
Publications: 2 Organism: Homo Sapiens
Pathways:Adipogenesis, Alzheimer Disease, Cell cycle: G1/S phase transition, Hedgehog, Insulin Receptor, MTOR Signaling, IGF and Myogenesis
+ up-regulates activity img/direct-activation.png phosphorylation GSK3B
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
Pathways:Adipogenesis, Insulin Receptor
+ up-regulates activity img/direct-activation.png phosphorylation GSK3B 0.28
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
+ down-regulates activity img/direct_inhibition.png binding GSK3B 0.39
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TSC2
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png binding GSK3B
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition GSK3B
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NfKb-p65/p50
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png unknown GSK3B
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png cleavage GSK3B
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EIF2B2 0.35
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EIF2B3 0.28
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EIF2B1 0.31
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation GLI3 0.20
Publications: 2 Organism: Drosophila Melanogaster, Mus Musculus
Pathways:Hedgehog
+ up-regulates activity img/direct-activation.png cleavage GSK3B
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png cleavage GSK3B
Publications: 1 Organism: Homo Sapiens
Pathways:Alzheimer Disease
+ up-regulates img/direct-activation.png phosphorylation, binding AXIN1 0.82
Publications: 3 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NEB 0.21
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding GSK3B/Axin/APC
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding MAPK14 0.25
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding MAP3K4 0.17
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition GSK3B
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NFATC2 0.24
Publications: 1 Organism: Homo Sapiens
Pathways:IGF and Myogenesis
+ up-regulates activity img/direct-activation.png relocalization GSK3B 0.20
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding GSK3B 0.50
Publications: 1 Organism: Homo Sapiens
Tissue: Brain, Kidney, Lung
+ up-regulates activity img/direct-activation.png binding GSK3B 0.66
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SMAD1
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding GSK3B 0.31
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png unknown GSK3B 0.07
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation APC 0.56
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition GSK3B
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition GSK3B
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CyclinD/CDK4
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G1/S phase transition, IGF and Myogenesis
+ up-regulates activity img/direct-activation.png phosphorylation GSK3B/Axin/APC
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B/Axin/APC
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png unknown GSK3B 0.03
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
Pathways:Adipogenesis, Insulin Receptor, MTOR Signaling
+ down-regulates img/direct_inhibition.png phosphorylation MAML1 0.17
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding GSK3B 0.23
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation NOTCH1 0.13
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation GSK3B 0.24
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png unknown GSK3B 0.16
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAFB 0.16
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAF 0.06
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EIF2B4 0.38
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAF 0.06
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAFB 0.16
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png unknown GSK3B 0.31
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding GSK3B 0.30
Publications: 1 Organism: Homo Sapiens