GSK3A glycogen synthase kinase 3 alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: GSK3Aprovided by HGNC
Official Full Name: glycogen synthase kinase 3 alphaprovided by HGNC
Primary source: HGNC:HGNC:4616
See related: Ensembl:ENSG00000105723 MIM:606784
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011]
Expression: Ubiquitous expression in brain (RPKM 26.3), testis (RPKM 18.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
109.20210226	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (42230186..42243330, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (42734342..42746754, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Glycogen synthase kinase (GSK) 3 in pregnancy and parturition: a systematic review of literature.
Title: Glycogen synthase kinase (GSK) 3 in pregnancy and parturition: a systematic review of literature.
GSK-3 is an RNA polymerase II phospho-CTD kinase.
Title: GSK-3 is an RNA polymerase II phospho-CTD kinase.
Diabetic patients showed a reduction in the ratio of Ser21-phosphorylated versus total GSK-3alpha, indicating enhanced GSK-3alpha activity in the presence of diabetes in human failing hearts.
Title: Glycogen Synthase Kinase-3α Promotes Fatty Acid Uptake and Lipotoxic Cardiomyopathy.
Single-cell transcriptome profiling revealed a direct impact on early neurogenesis and uncovered a selective role of GSK3 in the regulation of glutamatergic lineages and outer radial glia output.
Title: Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis.
Isoform-specific GSK3A activity is negatively correlated with human sperm motility.
Title: Isoform-specific GSK3A activity is negatively correlated with human sperm motility.
Hepatic expression of Akt (Thr308), GSK3beta (Ser9), and GSK3alpha (Ser21) did not correspond to progression of chronic hepatitis C to liver steatosis.
Title: Hepatic Expression of Phosphorylated Kinase Akt and Glycogen Synthase Kinase-3 Isoforms in Patients with Chronic Hepatitis C.
a pivotal role of GSK3 in the maturation of lung progenitors and provide novel insight into proximodistal specification during human lung development, is reported.
Title: Glycogen synthase kinase 3 induces multilineage maturation of human pluripotent stem cell-derived lung progenitors in 3D culture.
Here, the authors report that GSK3alpha and GSK3beta are acetylated at Lys246 and Lys183, respectively. They found that SIRT2 deacetylates GSK3beta, and thus enhances its binding to ATP.
Title: SIRT2 deacetylase regulates the activity of GSK3 isoforms independent of inhibitory phosphorylation.
Mitogen-activated protein kinases and glycogen synthase kinase 3 phosphorylate Gle1A and thereby coordinate stress granule dynamics by altering DDX3 function.
Title: MAPK- and glycogen synthase kinase 3-mediated phosphorylation regulates the DEAD-box protein modulator Gle1 for control of stress granule dynamics.
These results indicate that GSK3alpha functions as the primary isoform that regulates the expression of IL-10 in endothelial cells infected with S. aureus.
Title: Glycogen Synthase Kinase 3α Is the Main Isoform That Regulates the Transcription Factors Nuclear Factor-Kappa B and cAMP Response Element Binding in Bovine Endothelial Cells Infected with <i>Staphylococcus aureus</i>.

Submit: New GeneRIF Correction See all GeneRIFs (89)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Incubation of human macrophages with exogenous HIV-1 Nef protein induces phosphorylation of Akt and GSK-3ss, and promotes IL-10 release	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH78012 (e-PCR)
- UniSTS:7453

D19S656E (e-PCR)
- UniSTS:150570

D19S688E (e-PCR)
- UniSTS:150587

MARC_17709-17710:1031755211:1 (e-PCR)
- UniSTS:268383

D15S1477 (e-PCR)
- UniSTS:474482

SHGC-32066 (e-PCR)
- UniSTS:39032

RH11670 (e-PCR)
- UniSTS:39033

STS-T55612 (e-PCR)
- UniSTS:64144

RH45593 (e-PCR)
- UniSTS:42969

Homology

Homologs of the GSK3A gene: The GSK3A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 177 organisms have orthologs with human gene GSK3A
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase A catalytic subunit binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine kinase activity	IEA Inferred from Electronic Annotation more info
protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	NAS Non-traceable Author Statement more info	PubMed
protein threonine kinase activity	IEA Inferred from Electronic Annotation more info
signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
tau protein binding	NAS Non-traceable Author Statement more info	PubMed
tau-protein kinase activity	NAS Non-traceable Author Statement more info	PubMed
tau-protein kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
IRE1-mediated unfolded protein response	TAS Traceable Author Statement more info
Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
aging	IEA Inferred from Electronic Annotation more info
cardiac left ventricle morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
cell migration	IEA Inferred from Electronic Annotation more info
cellular response to insulin stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to interleukin-3	ISS Inferred from Sequence or Structural Similarity more info
cellular response to lithium ion	IEA Inferred from Electronic Annotation more info
dopamine receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
excitatory postsynaptic potential	NAS Non-traceable Author Statement more info	PubMed
extrinsic apoptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
extrinsic apoptotic signaling pathway in absence of ligand	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extrinsic apoptotic signaling pathway in absence of ligand	ISS Inferred from Sequence or Structural Similarity more info
glycogen metabolic process	IEA Inferred from Electronic Annotation more info
hypermethylation of CpG island	IEA Inferred from Electronic Annotation more info
insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
negative regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of UDP-glucose catabolic process	IC Inferred by Curator more info	PubMed
negative regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of canonical Wnt signaling pathway	TAS Traceable Author Statement more info	PubMed
negative regulation of cell growth involved in cardiac muscle cell development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of dendrite development	IEA Inferred from Electronic Annotation more info
negative regulation of glucose import	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of glycogen (starch) synthase activity	TAS Traceable Author Statement more info	PubMed
negative regulation of glycogen biosynthetic process	TAS Traceable Author Statement more info	PubMed
negative regulation of glycogen synthase activity, transferring glucose-1-phosphate	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of type B pancreatic cell development	TAS Traceable Author Statement more info	PubMed
nervous system development	IEA Inferred from Electronic Annotation more info
peptidyl-serine phosphorylation	IEA Inferred from Electronic Annotation more info
peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of amyloid-beta formation	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of amyloid-beta formation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of autophagy	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of glycogen (starch) synthase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of heart contraction	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of peptidyl-serine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of peptidyl-threonine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
positive regulation of protein targeting to mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
proteasome-mediated ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of autophagy of mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of gene expression by genetic imprinting	IEA Inferred from Electronic Annotation more info
regulation of neuron projection development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of systemic arterial blood pressure	ISS Inferred from Sequence or Structural Similarity more info
signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
apical dendrite	NAS Non-traceable Author Statement more info	PubMed
axon	IBA Inferred from Biological aspect of Ancestor more info	PubMed
beta-catenin destruction complex	NAS Non-traceable Author Statement more info	PubMed
beta-catenin destruction complex	TAS Traceable Author Statement more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	TAS Traceable Author Statement more info	PubMed
microtubule	IEA Inferred from Electronic Annotation more info
mitochondrion	IEA Inferred from Electronic Annotation more info
neuronal cell body	NAS Non-traceable Author Statement more info	PubMed
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
postsynapse	IEA Inferred from Electronic Annotation more info
proximal dendrite	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: glycogen synthase kinase-3 alpha

Names: GSK-3 alpha; serine/threonine-protein kinase GSK3A

NP_063937.2

EC 2.7.11.1

EC 2.7.11.26

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_019884.3 → NP_063937.2 glycogen synthase kinase-3 alpha

See identical proteins and their annotated locations for NP_063937.2

Status: VALIDATED

Source sequence(s)

AC006486, BC027984, D63424, L40027

Consensus CDS

CCDS12599.1

UniProtKB/Swiss-Prot

P49840

UniProtKB/TrEMBL

A0A024R0L5

Related

ENSP00000222330.3, ENST00000222330.8

Conserved Domains (2) summary

cd14137
Location:114 → 406

STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3

pfam00069
Location:119 → 403

Pkinase; Protein kinase domain