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Sep. 10, 2014:
A total of 174 experimentally verified S-nitrosylation sites on 94 S-nitrosylated proteins from individualized human colorectal cancer tissues using a label-free quantitation strategy.

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Protein Name: Glycogen synthase kinase-3 beta

UniprotKB/SwissProt ID: GSK3B_MOUSE (Q9WV60)

Gene Name: Gsk3b

Organism: Mus musculus (Mouse).

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. 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. 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 SFPQ at 'Thr-679' upon T-cell activation. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation.

Other Modifications: View all modification sites in dbPTM

Protein Subcellular Localization: Cytoplasm (By similarity). Nucleus (By similarity). Cell membrane (By similarity). Note=The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to

Network with metabolic pathway:
Kegg map ID Pathway Link
map05213Endometrial cancer
map05217Basal cell carcinoma
map04340Hedgehog signaling pathway
map04360Axon guidance
map04660T cell receptor signaling pathway
map04662B cell receptor signaling pathway
map04722Neurotrophin signaling pathway
map04728Dopaminergic synapse
map05160Hepatitis C
map05162Measles
map05210Colorectal cancer
map05215Prostate cancer
map04012ErbB signaling pathway
map04062Chemokine signaling pathway
map04110Cell cycle
map04151PI3K-Akt signaling pathway
map04310Wnt signaling pathway
map04510Focal adhesion
map04910Insulin signaling pathway
map04916Melanogenesis
map05010Alzheimer's disease
map05164Influenza A
map05166HTLV-I infection
map05169Epstein-Barr virus infection
map05200Pathways in cancer
Graphical Visualization of S-nitrosylation Sites:
Overview of Protein S-nitrosylation Sites with Functional and Structural Information
InterPro ID Domain
IPR000719
IPR002290
IPR008271
IPR011009

The S-nitrosylation sites of GSK3B_MOUSE

No. Position S-nitrosylated Peptide Secondary Structure of S-nitrosylated Peptide Solvent Accessibility of nitrosylated Site Substrate Motifs PubMed ID Experiment
1317PRTPPEAIAL C SRLLEYTPTA CCCCHHHHHH H HHHHHCCCCC 1.32%MC0621278135in vitro