GSK3A

Glycogen synthase kinase-3 alpha is an enzyme that in humans is encoded by the GSK3A gene.[5]

GSK3A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DFM
Identifiers
Aliases	GSK3A, Gsk3a, 2700086H06Rik, glycogen synthase kinase 3 alpha
External IDs	OMIM: 606784 MGI: 2152453 HomoloGene: 88581 GeneCards: GSK3A
EC number	2.7.11.1
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 42,230,190 bp[1] End 42,242,625 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 A3 Start 25,228,258 bp[2] End 25,237,851 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • nucleotide binding • protein kinase activity • kinase activity • protein serine/threonine kinase activity • tau-protein kinase activity • GO:0001948 protein binding • ATP binding • protein kinase binding • protein kinase A catalytic subunit binding • receptor binding • tau protein binding Cellular component • cytosol • beta-catenin destruction complex • postsynapse • mitochondrion • cytoplasm • microtubules • neuronal cell body • apical dendrite • proximal dendrite Biological process • positive regulation of protein catabolic process • phosphorylation • positive regulation of protein targeting to mitochondrion • chemical synaptic transmission, postsynaptic • negative regulation of UDP-glucose catabolic process • negative regulation of type B pancreatic cell development • Wnt signaling pathway • negative regulation of glycogen biosynthetic process • nervous system development • negative regulation of glycogen synthase activity, transferring glucose-1-phosphate • dopamine receptor signaling pathway • protein phosphorylation • IRE1-mediated unfolded protein response • negative regulation of glucose import • negative regulation of insulin receptor signaling pathway • regulation of autophagy of mitochondrion • negative regulation of glycogen (starch) synthase activity • cellular response to insulin stimulus • glycogen metabolic process • negative regulation of signal transduction • negative regulation of canonical Wnt signaling pathway • regulation of systemic arterial blood pressure • cardiac left ventricle morphogenesis • regulation of gene expression by genetic imprinting • aging • insulin receptor signaling pathway • positive regulation of peptidyl-threonine phosphorylation • cell migration • negative regulation of TOR signaling • positive regulation of peptidyl-serine phosphorylation • cellular response to interleukin-3 • proteasome-mediated ubiquitin-dependent protein catabolic process • positive regulation of neuron apoptotic process • hypermethylation of CpG island • positive regulation of heart contraction • positive regulation of transcription from RNA polymerase II promoter • negative regulation of cell growth involved in cardiac muscle cell development • cellular response to lithium ion • cellular response to organic cyclic compound • positive regulation of adrenergic receptor signaling pathway • extrinsic apoptotic signaling pathway in absence of ligand • positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway • negative regulation of dendrite development • positive regulation of glycogen (starch) synthase activity • carbohydrate metabolic process • positive regulation of gene expression • peptidyl-threonine phosphorylation • positive regulation of protein ubiquitination • positive regulation of proteasomal ubiquitin-dependent protein catabolic process • excitatory postsynaptic potential • extrinsic apoptotic signaling pathway • positive regulation of adenylate cyclase-activating G-protein coupled receptor signaling pathway • positive regulation of amyloid-beta formation • positive regulation of autophagy Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2931	606496
Ensembl	ENSG00000105723	ENSMUSG00000057177
UniProt	P49840	Q2NL51
RefSeq (mRNA)	NM_019884	NM_001031667
RefSeq (protein)	NP_063937	NP_001026837
Location (UCSC)	Chr 19: 42.23 – 42.24 Mb	Chr 7: 25.23 – 25.24 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Glycogen synthase kinase 3-alpha EC 2.7.1.37 is a multifunctional protein serine kinase, homologous to Drosophila 'shaggy' (zeste-white3) and implicated in the control of several regulatory proteins including glycogen synthase and various transcription factors (e.g., JUN). It also plays a role in the WNT and phosphoinositide 3-kinase (especially PIK3CG) signaling pathways.[6][7]

Model organisms

Gsk3a knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Homozygous Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
All tests and analysis from[8][9]

Model organisms have been used in the study of GSK3A function. A conditional knockout mouse line, called Gsk3a^{tm1a(EUCOMM)Wtsi}[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty one tests were carried out on mutant mice but no significant abnormalities were observed.[8]

See also

• Glycogen synthase kinase 3

References

1. GRCh38: Ensembl release 89: ENSG00000105723 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057177 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Shaw PC, Davies AF, Lau KF, Garcia-Barcelo M, Waye MM, Lovestone S, Miller CC, Anderton BH (Oct 1998). "Isolation and chromosomal mapping of human glycogen synthase kinase-3 alpha and -3 beta encoding genes". Genome. 41 (5): 720–7. doi:10.1139/gen-41-5-720. PMID 9809441.
6. Ali A, Hoeflich KP, Woodgett JR (Aug 2001). "Glycogen synthase kinase-3: properties, functions, and regulation". Chemical Reviews. 101 (8): 2527–40. doi:10.1021/cr000110o. PMID 11749387.
7. "Entrez Gene: GSK3A glycogen synthase kinase 3 alpha".
8. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
9. Mouse Resources Portal, Wellcome Trust Sanger Institute.
10. "International Knockout Mouse Consortium".
11. "Mouse Genome Informatics".
12. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
13. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
14. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
15. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.