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Q2NL51

- GSK3A_MOUSE

UniProt

Q2NL51 - GSK3A_MOUSE

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Protein

Glycogen synthase kinase-3 alpha

Gene

Gsk3a

Organism
Mus musculus (Mouse)
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.4 Publications

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.

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 activity Source: MGI
  3. protein serine/threonine kinase activity Source: UniProtKB
  4. tau-protein kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. cardiac left ventricle morphogenesis Source: BHF-UCL
  2. cell migration Source: MGI
  3. cellular response to interleukin-3 Source: UniProtKB
  4. cellular response to lithium ion Source: MGI
  5. cellular response to organic cyclic compound Source: MGI
  6. extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  7. glycogen metabolic process Source: UniProtKB-KW
  8. hypermethylation of CpG island Source: BHF-UCL
  9. insulin receptor signaling pathway Source: BHF-UCL
  10. negative regulation of cell growth involved in cardiac muscle cell development Source: BHF-UCL
  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: BHF-UCL
  14. negative regulation of transferase activity Source: Ensembl
  15. nervous system development Source: UniProtKB-KW
  16. positive regulation of adrenergic receptor signaling pathway Source: BHF-UCL
  17. positive regulation of cAMP biosynthetic process Source: BHF-UCL
  18. positive regulation of glycogen (starch) synthase activity Source: BHF-UCL
  19. positive regulation of heart contraction Source: BHF-UCL
  20. positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
  21. positive regulation of peptidyl-serine phosphorylation Source: MGI
  22. positive regulation of peptidyl-threonine phosphorylation Source: MGI
  23. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  24. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  25. protein phosphorylation Source: UniProtKB
  26. regulation of gene expression by genetic imprinting Source: BHF-UCL
  27. regulation of systemic arterial blood pressure Source: BHF-UCL
  28. 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

ReactomeiREACT_106572. XBP1(S) activates chaperone genes.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_220918. AKT phosphorylates targets in the cytosol.

Names & Taxonomyi

Protein namesi
Recommended name:
Glycogen synthase kinase-3 alpha (EC:2.7.11.26)
Short name:
GSK-3 alpha
Alternative name(s):
Serine/threonine-protein kinase GSK3A (EC:2.7.11.1)
Gene namesi
Name:Gsk3a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:2152453. Gsk3a.

Pathology & Biotechi

Disruption phenotypei

Enhanced glucose tolerance and insulin sensitivity, increased activity of hepatic glycogen synthase, elevated hepatic glycogen storage and reduced fat mass.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi21 – 211S → A: Loss of phosphorylation; No inhibition of activity and constitutively active. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 490489Glycogen synthase kinase-3 alphaPRO_0000280395Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei21 – 211Phosphoserine; by PKB/AKT11 Publication
Modified residuei72 – 721PhosphoserineBy similarity
Modified residuei77 – 771PhosphoserineBy similarity
Modified residuei97 – 971PhosphoserineBy similarity
Modified residuei279 – 2791PhosphotyrosineBy similarity

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-279.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ2NL51.
PaxDbiQ2NL51.
PRIDEiQ2NL51.

PTM databases

PhosphoSiteiQ2NL51.

Miscellaneous databases

PMAP-CutDBQ2NL51.

Expressioni

Gene expression databases

BgeeiQ2NL51.
CleanExiMM_GSK3A.
ExpressionAtlasiQ2NL51. baseline.
GenevestigatoriQ2NL51.

Interactioni

Subunit structurei

Monomer. Interacts with AXIN1 and CTNNB1/beta-catenin (By similarity). Interacts with ARRB2.By similarity1 Publication

Protein-protein interaction databases

BioGridi546781. 3 interactions.
IntActiQ2NL51. 1 interaction.
STRINGi10090.ENSMUSP00000071654.

Structurei

3D structure databases

ProteinModelPortaliQ2NL51.
SMRiQ2NL51. Positions 99-447.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini119 – 404286Protein 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.
GeneTreeiENSGT00520000055635.
HOGENOMiHOG000233017.
HOVERGENiHBG014652.
InParanoidiQ2NL51.
KOiK08822.
OMAiFDELRCP.
OrthoDBiEOG7TF78V.
PhylomeDBiQ2NL51.
TreeFamiTF101104.

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.

Q2NL51-1 [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
TTVVATVGQG PERSQEVAYT DIKVIGNGSF GVVYQARLAE TRELVAIKKV
160 170 180 190 200
LQDKRFKNRE LQIMRKLDHC NIVRLRYFFY SSGEKKDELY LNLVLEYVPE
210 220 230 240 250
TVYRVARHFT KAKLITPIIY IKVYMYQLFR 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 SKTPPEAIAL CSSLLEYTPS SRLSPLEACA
410 420 430 440 450
HSFFDELRRL GAQLPNDRPL PPLFNFSPGE LSIQPSLNAI LIPPHLRSPA
460 470 480 490
GPASPLTTSY NPSSQALTEA QTGQDWQPSD ATTATLASSS
Length:490
Mass (Da):51,661
Last modified:March 20, 2007 - v2
Checksum:i739CDD86BBFB497B
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC156992 Genomic DNA. No translation available.
BC111032 mRNA. Translation: AAI11033.1.
CCDSiCCDS20976.1.
RefSeqiNP_001026837.1. NM_001031667.1.
UniGeneiMm.491101.

Genome annotation databases

EnsembliENSMUST00000071739; ENSMUSP00000071654; ENSMUSG00000057177.
GeneIDi606496.
KEGGimmu:606496.
UCSCiuc009frx.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC156992 Genomic DNA. No translation available.
BC111032 mRNA. Translation: AAI11033.1 .
CCDSi CCDS20976.1.
RefSeqi NP_001026837.1. NM_001031667.1.
UniGenei Mm.491101.

3D structure databases

ProteinModelPortali Q2NL51.
SMRi Q2NL51. Positions 99-447.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 546781. 3 interactions.
IntActi Q2NL51. 1 interaction.
STRINGi 10090.ENSMUSP00000071654.

Chemistry

ChEMBLi CHEMBL2176843.

PTM databases

PhosphoSitei Q2NL51.

Proteomic databases

MaxQBi Q2NL51.
PaxDbi Q2NL51.
PRIDEi Q2NL51.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000071739 ; ENSMUSP00000071654 ; ENSMUSG00000057177 .
GeneIDi 606496.
KEGGi mmu:606496.
UCSCi uc009frx.1. mouse.

Organism-specific databases

CTDi 2931.
MGIi MGI:2152453. Gsk3a.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00520000055635.
HOGENOMi HOG000233017.
HOVERGENi HBG014652.
InParanoidi Q2NL51.
KOi K08822.
OMAi FDELRCP.
OrthoDBi EOG7TF78V.
PhylomeDBi Q2NL51.
TreeFami TF101104.

Enzyme and pathway databases

Reactomei REACT_106572. XBP1(S) activates chaperone genes.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_220918. AKT phosphorylates targets in the cytosol.

Miscellaneous databases

NextBioi 414454.
PMAP-CutDB Q2NL51.
PROi Q2NL51.
SOURCEi Search...

Gene expression databases

Bgeei Q2NL51.
CleanExi MM_GSK3A.
ExpressionAtlasi Q2NL51. baseline.
Genevestigatori Q2NL51.

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

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 227-490.
    Tissue: Eye.
  3. "An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior."
    Beaulieu J.-M., Sotnikova T.D., Marion S., Lefkowitz R.J., Gainetdinov R.R., Caron M.G.
    Cell 122:261-273(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB2.
  4. "Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis."
    McManus E.J., Sakamoto K., Armit L.J., Ronaldson L., Shpiro N., Marquez R., Alessi D.R.
    EMBO J. 24:1571-1583(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF SER-21, PHOSPHORYLATION AT SER-21.
  5. "Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1."
    Maurer U., Charvet C., Wagman A.S., Dejardin E., Green D.R.
    Mol. Cell 21:749-760(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN MCL1 PHOSPHORYLATION.
  6. "GSK3 alpha and GSK3 beta are necessary for axon formation."
    Garrido J.J., Simon D., Varea O., Wandosell F.
    FEBS Lett. 581:1579-1586(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN AXON FORMATION, TISSUE SPECIFICITY.
  7. "Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism."
    MacAulay K., Doble B.W., Patel S., Hansotia T., Sinclair E.M., Drucker D.J., Nagy A., Woodgett J.R.
    Cell Metab. 6:329-337(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HEPATIC GLYCOGEN METABOLISM, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiGSK3A_MOUSE
AccessioniPrimary (citable) accession number: Q2NL51
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: October 29, 2014
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3