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P18265 (GSK3A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycogen synthase kinase-3 alpha

Short name=GSK-3 alpha
EC=2.7.11.26
Alternative name(s):
Factor A
Short name=FA
Serine/threonine-protein kinase GSK3A
EC=2.7.11.1
Gene names
Name:Gsk3a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length483 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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. Ref.3

Catalytic activity

ATP + [tau protein] = ADP + [tau protein] phosphate.

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated by phosphorylation at Tyr-279. In response to insulin, inhibited by phosphorylation at Ser-21 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium By similarity.

Subunit structure

Monomer. Interacts with ARRB2, AXIN1 and CTNNB1/beta-catenin By similarity.

Post-translational modification

Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3A, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-279 By similarity. Ref.2

Miscellaneous

Simultaneous silencing of GSK3A and GSK3B by RNAi stimulates replication and promotes survival of INS-1E pancreatic beta cells (Ref.3).

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processCarbohydrate metabolism
Glycogen metabolism
Neurogenesis
Wnt signaling pathway
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Signal transduction inhibitor
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cardiac left ventricle morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from electronic annotation. Source: Ensembl

cellular response to interleukin-3

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to lithium ion

Inferred from electronic annotation. Source: Ensembl

cellular response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from sequence or structural similarity. Source: UniProtKB

glycogen metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

hypermethylation of CpG island

Inferred from electronic annotation. Source: Ensembl

insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of TOR signaling

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth involved in cardiac muscle cell development

Inferred from electronic annotation. Source: Ensembl

nervous system development

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of adrenergic receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cAMP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of glycogen (starch) synthase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of heart contraction

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 11035810. Source: BHF-UCL

regulation of gene expression by genetic imprinting

Inferred from electronic annotation. Source: Ensembl

regulation of systemic arterial blood pressure

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.1. Source: RGD

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase A catalytic subunit binding

Inferred from physical interaction PubMed 11035810. Source: BHF-UCL

protein serine/threonine kinase activity

Inferred from direct assay PubMed 11035810. Source: BHF-UCL

tau-protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 483482Glycogen synthase kinase-3 alpha
PRO_0000085979

Regions

Domain119 – 403285Protein kinase
Nucleotide binding125 – 1339ATP By similarity
Compositional bias3 – 8381Gly-rich

Sites

Active site2441Proton acceptor By similarity
Binding site1481ATP By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue21Phosphoserine By similarity
Modified residue211Phosphoserine; by PKB/AKT1 By similarity
Modified residue721Phosphoserine By similarity
Modified residue771Phosphoserine By similarity
Modified residue971Phosphoserine By similarity
Modified residue2791Phosphotyrosine Ref.2

Sequences

Sequence LengthMass (Da)Tools
P18265 [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: A98DC1C5C7F7B716

FASTA48351,027
        10         20         30         40         50         60 
MSGGGPSGGG PGGSGRARTS SFAEPGGGGG GGGGGPGGSA SGPGGTGGGK ASVGAMGGGV 

        70         80         90        100        110        120 
GASSSGGGPS GSGGGGSGGP GAGTSFPPPG VKLGRDSGKV TTVVATLGQG PERSQEVAYT 

       130        140        150        160        170        180 
DIKVIGNGSF GVVYQARLAE TRELVAIKKV LQDKRFKNRE LQIMRKLDHC NIVRLRYFFY 

       190        200        210        220        230        240 
SSGEKKDELY LNLVLEYVPE TVYRVARHFT KAKLIIPIIY VKVYMYQLFR SLAYIHSQGV 

       250        260        270        280        290        300 
CHRDIKPQNL LVDPDTAVLK LCDFGSAKQL VRGEPNVSYI CSRYYRAPEL IFGATDYTSS 

       310        320        330        340        350        360 
IDVWSAGCVL AELLLGQPIF PGDSGVDQLV EIIKVLGTPT REQIREMNPN YTEFKFPQIK 

       370        380        390        400        410        420 
AHPWTKVFKS RTPPEAIALC SSLLEYTPSS RLSPLEACAH SFFDELRSLG TQLPNNRPLP 

       430        440        450        460        470        480 
PLFNFSPGEL SIQPSLNAIL IPPHLRSPSG PATLTSSSQA LTETQTGQDW QAPDATPTLT 


NSS 

« Hide

References

[1]"Molecular cloning and expression of glycogen synthase kinase-3/factor A."
Woodgett J.R.
EMBO J. 9:2431-2438(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation."
Hughes K., Nikolakaki E., Plyte S.E., Totty N.F., Woodgett J.R.
EMBO J. 12:803-808(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-279.
[3]"Inhibition of GSK3 promotes replication and survival of pancreatic beta cells."
Mussmann R., Geese M., Harder F., Kegel S., Andag U., Lomow A., Burk U., Onichtchouk D., Dohrmann C., Austen M.
J. Biol. Chem. 282:12030-12037(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF PANCREATIC BETA-CELLS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X53427 mRNA. Translation: CAA37518.1.
PIRTVRTKA. S14707.
RefSeqNP_059040.1. NM_017344.1.
UniGeneRn.36807.

3D structure databases

ProteinModelPortalP18265.
SMRP18265. Positions 99-446.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-1072N.
IntActP18265. 2 interactions.
MINTMINT-1532463.
STRING10116.ENSRNOP00000027677.

Chemistry

ChEMBLCHEMBL1075224.

PTM databases

PhosphoSiteP18265.

Proteomic databases

PaxDbP18265.
PRIDEP18265.

Protocols and materials databases

DNASU50686.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID50686.
KEGGrno:50686.
UCSCRGD:620351. rat.

Organism-specific databases

CTD2931.
RGD620351. Gsk3a.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233017.
HOVERGENHBG014652.
InParanoidP18265.
KOK08822.
PhylomeDBP18265.

Enzyme and pathway databases

BRENDA2.7.11.26. 5301.
ReactomeREACT_206767. Disease.
REACT_212996. Signal Transduction.
REACT_227097. Immune System.

Gene expression databases

GenevestigatorP18265.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio610536.
PROP18265.

Entry information

Entry nameGSK3A_RAT
AccessionPrimary (citable) accession number: P18265
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: May 14, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families