Aliases for GSK3B Gene
External Ids for GSK3B Gene
The protein encoded by this gene is a serine-threonine kinase, belonging to the glycogen synthase kinase subfamily. It is involved in energy metabolism, neuronal cell development, and body pattern formation. Polymorphisms in this gene have been implicated in modifying risk of Parkinson disease, and studies in mice show that overexpression of this gene may be relevant to the pathogenesis of Alzheimer disease. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
GeneCards Summary for GSK3B Gene
GSK3B (Glycogen Synthase Kinase 3 Beta) is a Protein Coding gene. Diseases associated with GSK3B include aneurysmal bone cysts and waardenburg's syndrome. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include identical protein binding and protein kinase binding. An important paralog of this gene is GSK3A.
UniProtKB/Swiss-Prot for GSK3B Gene
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.
Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (alpha and beta), was originally discovered as a key enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cell division, proliferation, motility and survival. GSK-3 plays a role in a number of pathological conditions including cancer and diabetes and is increasingly seen as an important component of neurological diseases. GSK-3 phosphorylates tau and presenilin-1, which are involved in the development of Alzheimers disease. Both isoforms of GSK-3 are ubiquitously expressed, although particularly high levels of GSK-3beta are found in the brain where it is involved in synaptic plasticity, possibly via regulation of NMDA receptor trafficking. GSK-3 phosphorylates over 40 different substrates including signaling proteins, transcription factors and structural proteins, and is part of the signal transduction cascade of a large number of growth factors and cytokines. The activity of GSK is regulated by phosphorylation (Akt, S6K, RSK, PKA and PKC), dephosphorylation (PP1 and PP2A), and by binding to protein complexes (with beta-catenin, axin, CK1 and the APC complex).