Target name

P49841: Glycogen synthase kinase-3 beta


  Protein 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).

  Database links

Uniprot primary ID P49841
PDB ID 3SAY 3E8D 3Q3B 2XH5 1Q3W 3MV5 1R0E 3F88 1GNG 1Q5K 4B7T 1Q3D 3F7Z 1Q41 2JDR 2UW9 3ZDI 3M1S 2O5K 3SD0 2JDO 3L1S 4NM5 4NM7 4NM0 4NM3 1I09 2JLD 3I4B 3CQU 3CQW 3OW4 4PTE 4DIT 1O9U 4PTC 3ZRM 3ZRL 4EKK 1Q4L 2OW3 4J1R 1J1B 1O6K 4J71 1PYX 1O6L 4AFJ 3QKK 3E87 4IQ6
DrugBank ID DB01356
BioGrid ID 109187
GuidetoPHARMACOLOGY ID 2030
PharmGKB ID PA29009
KEGG ID hsa:2932
DIP ID DIP-878N
STRING ID 9606.ENSP00000324806
IntAct ID P49841
DMDM 20455502
BRENDA 2.7.11.26
Reactome R-HSA-5358752 R-HSA-5610783 R-HSA-5358751 R-HSA-5339716 R-HSA-5358747 R-HSA-5610785 R-HSA-5358749 R-HSA-195253 R-HSA-196299 R-HSA-5467340 R-HSA-5674400 R-HSA-198323 R-HSA-399956 R-HSA-4641262 R-HSA-3371453 R-HSA-5467348 R-HSA-5467337
SignaLink P49841
BioCyc
Entrez Gene (Gene ID) 2932
BindingDB P49841

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.858 0.004 0.822 0.000 0.840 0.000 0.841 0.003 0.912 0.004 0.680 0.005 Download
Estate fingerprints 0.780 0.000 0.720 0.000 0.750 0.000 0.760 0.000 0.830 0.000 0.507 0.005 Download
MACCS fingerprints 0.760 0.000 0.780 0.000 0.770 0.000 0.770 0.000 0.851 0.003 0.540 0.000 Download
Daylight fingerprints 0.780 0.000 0.700 0.000 0.740 0.000 0.750 0.000 0.790 0.000 0.480 0.000 Download
ECFP2 fingerprints 0.918 0.004 0.812 0.000 0.865 0.005 0.870 0.000 0.940 0.000 0.734 0.005 Download
ECFP4 fingerprints 0.911 0.003 0.909 0.000 0.910 0.000 0.910 0.000 0.970 0.000 0.821 0.003 Download
ECFP6 fingerprints 0.882 0.004 0.936 0.005 0.909 0.003 0.903 0.005 0.960 0.000 0.813 0.005 Download

  Download datasets

Positive dataset Negative dataset


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School of Pharmaceutical Sciences, Central South University. All rights reserved.

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