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P18265

- GSK3A_RAT

UniProt

P18265 - GSK3A_RAT

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
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 1 (01 Nov 1990)
      Previous versions | rss
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    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 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

    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

    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

    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_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: October 1, 2014
    This is version 127 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