General Information of the Protein
Protein ID
PT00931
Protein Name
Glycogen synthase kinase-3 alpha
Secondarily
Protein Name
Serine/threonine-protein kinase GSK3A
Gene Name
GSK3A
Sequence
MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGVCHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLPPLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLTNSS
    Show/Hide
Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CMGC protein kinase group
>
CMGC protein kinase GSK family
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), CTNNB1/beta-catenin, APC and AXIN1 (PubMed:11749387, PubMed:17478001, PubMed:19366350). Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350). Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions which activates KAT5/TIP60 acetyltransferase activity and promotes acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075).
    Show/Hide
Uniprot ID
Primary ID:
P49840

Secondarily ID:
O14959
    Show/Hide
Ensembl ID
ENSG00000105723
HGNC ID
HGNC:4616
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000025 , HEK-293T
Compound ID Compound Name Compound Formula
CP0109175
3-[(3-chlorophenyl)amino]-4-(2-methoxyphenyl)-2,5-dihydro-1H-pyrrole-2,5-dione
   Show/Hide
C17H13ClN2O3
 1
1
IC50 = 5300 nM
   TI
   LI
   LO
   TS
CP0011976
3-[[4-(2-methoxyphenyl)-2,5-dioxopyrrol-3-yl]amino]benzonitrile
   Show/Hide
C18H13N3O3
 1
1
IC50 = 14000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0109175
3-[(3-chlorophenyl)amino]-4-(2-methoxyphenyl)-2,5-dihydro-1H-pyrrole-2,5-dione
   Show/Hide
C17H13ClN2O3
 1
1 IC50 = 14 nM
CP0011976
3-[[4-(2-methoxyphenyl)-2,5-dioxopyrrol-3-yl]amino]benzonitrile
   Show/Hide
C18H13N3O3
 1
1 IC50 = 19 nM
Clinical Information about the Protein
Target 1 ( Glycogen synthase kinase-3 alpha (GSK-3A) )
Target Type Successful Target
Disease 5 Target-related Diseases  5
1 Epilepsy [ICD-11: 8A60-8A68]
2 Acute myeloid leukaemia [ICD-11: 2A60]
3 Ovarian cancer [ICD-11: 2C73]
4 Graft rejection [ICD-11: NE84]
5 Malignant glioma [ICD-11: 2A00.0]
Approved Drug(s) 1 Approved Drug  1
1 Valproate Approved
Epilepsy
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 LY2090314 Phase 2
Acute myeloid leukaemia
Patented Agent(s) 3 Patented Agents  3
1 AR-A014418 Patented
Ovarian cancer
2 CHIR-99021 Patented
Graft rejection
3 TDZD-8 Patented
Malignant glioma
Target 2 ( GSK3A messenger RNA (GSK3A mRNA) )
Target Type Literature-reported Target