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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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei148 – 1481ATPPROSITE-ProRule annotation
Active sitei244 – 2441Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi125 – 1339ATPPROSITE-ProRule annotation

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 glucose import Source: Ensembl
  12. negative regulation of insulin receptor signaling pathway Source: Ensembl
  13. negative regulation of TOR signaling Source: Ensembl
  14. negative regulation of transferase activity Source: Ensembl
  15. nervous system development Source: UniProtKB-KW
  16. positive regulation of adrenergic receptor signaling pathway Source: Ensembl
  17. positive regulation of cAMP biosynthetic process Source: Ensembl
  18. positive regulation of glycogen (starch) synthase activity Source: Ensembl
  19. positive regulation of heart contraction Source: Ensembl
  20. positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
  21. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  22. positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
  23. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  24. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  25. protein phosphorylation Source: BHF-UCL
  26. regulation of gene expression by genetic imprinting Source: Ensembl
  27. regulation of systemic arterial blood pressure Source: Ensembl
  28. signal transduction Source: RGD
  29. 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_252972. AKT phosphorylates targets in the cytosol.
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 – 11RemovedBy similarity
Chaini2 – 483482Glycogen synthase kinase-3 alphaPRO_0000085979Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei21 – 211Phosphoserine; by PKB/AKT1By similarity
Modified residuei72 – 721PhosphoserineBy similarity
Modified residuei77 – 771PhosphoserineBy similarity
Modified residuei97 – 971PhosphoserineBy 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).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP18265.
PRIDEiP18265.

PTM databases

PhosphoSiteiP18265.

Expressioni

Gene expression databases

ExpressionAtlasiP18265. baseline.
GenevestigatoriP18265.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP18265.
SMRiP18265. Positions 99-446.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini119 – 403285Protein kinasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

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.
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

« Hide

        10         20         30         40         50
MSGGGPSGGG PGGSGRARTS SFAEPGGGGG GGGGGPGGSA SGPGGTGGGK
60 70 80 90 100
ASVGAMGGGV GASSSGGGPS GSGGGGSGGP GAGTSFPPPG VKLGRDSGKV
110 120 130 140 150
TTVVATLGQG PERSQEVAYT DIKVIGNGSF GVVYQARLAE TRELVAIKKV
160 170 180 190 200
LQDKRFKNRE LQIMRKLDHC NIVRLRYFFY SSGEKKDELY LNLVLEYVPE
210 220 230 240 250
TVYRVARHFT KAKLIIPIIY VKVYMYQLFR SLAYIHSQGV CHRDIKPQNL
260 270 280 290 300
LVDPDTAVLK LCDFGSAKQL VRGEPNVSYI CSRYYRAPEL IFGATDYTSS
310 320 330 340 350
IDVWSAGCVL AELLLGQPIF PGDSGVDQLV EIIKVLGTPT REQIREMNPN
360 370 380 390 400
YTEFKFPQIK AHPWTKVFKS RTPPEAIALC SSLLEYTPSS RLSPLEACAH
410 420 430 440 450
SFFDELRSLG TQLPNNRPLP PLFNFSPGEL SIQPSLNAIL IPPHLRSPSG
460 470 480
PATLTSSSQA LTETQTGQDW QAPDATPTLT NSS
Length:483
Mass (Da):51,027
Last modified:November 1, 1990 - v1
Checksum:iA98DC1C5C7F7B716
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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_252972. AKT phosphorylates targets in the cytosol.
REACT_93415. XBP1(S) activates chaperone genes.

Miscellaneous databases

NextBioi 610536.
PROi P18265.

Gene expression databases

ExpressionAtlasi P18265. baseline.
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.
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: November 26, 2014
This is version 129 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