Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

GSK3A (P49840) - Overview - Molecular Target Synopsis

Protein


GSK3A, Glycogen synthase kinase-3 alpha
Enzyme Classification 2.7.11.26
UniProt P49840

Also Known as GSK3A_HUMAN, GSK3A

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. Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Monomer. Interacts with ARRB2 (By similarity). Interacts with AXIN1 and CTNNB1/beta-catenin. Interacts with CTNND2 (PubMed:19706605).

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
483ENSG00000105723ENST00000453535, ENST00000222330ENSP00000412663, ENSP00000222330P49840-1
401ENSG00000105723ENST00000398249ENSP00000381301

Drugs


GSK3A is targeted by Approved Drug Lithium Citrate. (see details)
Lithium Citrate

Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project GSK3A has gain in 4 cell-lines, loss in 1 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, A549, SN12C

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK-N-FI, G142, NCI-H1299

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: A549, SK-N-SH, HUVEC

(see details)

RNA Interference


GSK3A was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: PCI30, TOV112D. (see details)

3D Structures


At greater than 75% identity similarity to GSK3A there are:
65 structures (121 chains) solved
63 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


GSK3A has been screened with 1787 compounds (2735 bioactivities), 467 compounds have bioactivities that show binding affinity of <= 500nM (590 bioactivities). (see details)