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P18265

- GSK3A_RAT

UniProt

P18265 - GSK3A_RAT

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Protein

Glycogen synthase kinase-3 alpha

Gene
Gsk3a
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei148 – 1481ATP By similarity
Active sitei244 – 2441Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi125 – 1339ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein kinase A catalytic subunit binding Source: BHF-UCL
  3. protein serine/threonine kinase activity Source: BHF-UCL
  4. tau-protein kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. cardiac left ventricle morphogenesis Source: Ensembl
  2. cell migration Source: Ensembl
  3. cellular response to interleukin-3 Source: UniProtKB
  4. cellular response to lithium ion Source: Ensembl
  5. cellular response to organic cyclic compound Source: Ensembl
  6. extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  7. glycogen metabolic process Source: UniProtKB-KW
  8. hypermethylation of CpG island Source: Ensembl
  9. insulin receptor signaling pathway Source: Ensembl
  10. negative regulation of cell growth involved in cardiac muscle cell development Source: Ensembl
  11. negative regulation of TOR signaling Source: Ensembl
  12. nervous system development Source: UniProtKB-KW
  13. positive regulation of adrenergic receptor signaling pathway Source: Ensembl
  14. positive regulation of cAMP biosynthetic process Source: Ensembl
  15. positive regulation of glycogen (starch) synthase activity Source: Ensembl
  16. positive regulation of heart contraction Source: Ensembl
  17. positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
  18. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  19. positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
  20. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  21. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  22. protein phosphorylation Source: BHF-UCL
  23. regulation of gene expression by genetic imprinting Source: Ensembl
  24. regulation of systemic arterial blood pressure Source: Ensembl
  25. signal transduction Source: RGD
  26. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Signal transduction inhibitor, Transferase

Keywords - Biological processi

Carbohydrate metabolism, Glycogen metabolism, Neurogenesis, Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.26. 5301.
ReactomeiREACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_93415. XBP1(S) activates chaperone genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Glycogen synthase kinase-3 alpha (EC:2.7.11.26)
Short name:
GSK-3 alpha
Alternative name(s):
Factor A
Short name:
FA
Serine/threonine-protein kinase GSK3A (EC:2.7.11.1)
Gene namesi
Name:Gsk3a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi620351. Gsk3a.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 483482Glycogen synthase kinase-3 alphaPRO_0000085979Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine By similarity
Modified residuei2 – 21Phosphoserine By similarity
Modified residuei21 – 211Phosphoserine; by PKB/AKT1 By similarity
Modified residuei72 – 721Phosphoserine By similarity
Modified residuei77 – 771Phosphoserine By similarity
Modified residuei97 – 971Phosphoserine By similarity
Modified residuei279 – 2791Phosphotyrosine1 Publication

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP18265.
PRIDEiP18265.

PTM databases

PhosphoSiteiP18265.

Expressioni

Gene expression databases

GenevestigatoriP18265.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

DIPiDIP-1072N.
IntActiP18265. 2 interactions.
MINTiMINT-1532463.
STRINGi10116.ENSRNOP00000027677.

Structurei

3D structure databases

ProteinModelPortaliP18265.
SMRiP18265. Positions 99-446.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini119 – 403285Protein kinaseAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi3 – 8381Gly-richAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233017.
HOVERGENiHBG014652.
InParanoidiP18265.
KOiK08822.
PhylomeDBiP18265.

Family and domain databases

InterProiIPR011009. 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]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P18265-1 [UniParc]FASTAAdd to Basket

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MSGGGPSGGG PGGSGRARTS SFAEPGGGGG GGGGGPGGSA SGPGGTGGGK    50
ASVGAMGGGV GASSSGGGPS GSGGGGSGGP GAGTSFPPPG VKLGRDSGKV 100
TTVVATLGQG PERSQEVAYT DIKVIGNGSF GVVYQARLAE TRELVAIKKV 150
LQDKRFKNRE LQIMRKLDHC NIVRLRYFFY SSGEKKDELY LNLVLEYVPE 200
TVYRVARHFT KAKLIIPIIY VKVYMYQLFR SLAYIHSQGV CHRDIKPQNL 250
LVDPDTAVLK LCDFGSAKQL VRGEPNVSYI CSRYYRAPEL IFGATDYTSS 300
IDVWSAGCVL AELLLGQPIF PGDSGVDQLV EIIKVLGTPT REQIREMNPN 350
YTEFKFPQIK AHPWTKVFKS RTPPEAIALC SSLLEYTPSS RLSPLEACAH 400
SFFDELRSLG TQLPNNRPLP PLFNFSPGEL SIQPSLNAIL IPPHLRSPSG 450
PATLTSSSQA LTETQTGQDW QAPDATPTLT NSS 483
Length:483
Mass (Da):51,027
Last modified:November 1, 1990 - v1
Checksum:iA98DC1C5C7F7B716
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X53427 mRNA. Translation: CAA37518.1.
PIRiS14707. TVRTKA.
RefSeqiNP_059040.1. NM_017344.1.
UniGeneiRn.36807.

Genome annotation databases

GeneIDi50686.
KEGGirno:50686.
UCSCiRGD:620351. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X53427 mRNA. Translation: CAA37518.1 .
PIRi S14707. TVRTKA.
RefSeqi NP_059040.1. NM_017344.1.
UniGenei Rn.36807.

3D structure databases

ProteinModelPortali P18265.
SMRi P18265. Positions 99-446.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-1072N.
IntActi P18265. 2 interactions.
MINTi MINT-1532463.
STRINGi 10116.ENSRNOP00000027677.

Chemistry

ChEMBLi CHEMBL1075224.

PTM databases

PhosphoSitei P18265.

Proteomic databases

PaxDbi P18265.
PRIDEi P18265.

Protocols and materials databases

DNASUi 50686.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 50686.
KEGGi rno:50686.
UCSCi RGD:620351. rat.

Organism-specific databases

CTDi 2931.
RGDi 620351. Gsk3a.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233017.
HOVERGENi HBG014652.
InParanoidi P18265.
KOi K08822.
PhylomeDBi P18265.

Enzyme and pathway databases

BRENDAi 2.7.11.26. 5301.
Reactomei REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_93415. XBP1(S) activates chaperone genes.

Miscellaneous databases

NextBioi 610536.
PROi P18265.

Gene expression databases

Genevestigatori P18265.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiGSK3A_RAT
AccessioniPrimary (citable) accession number: P18265
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: September 3, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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