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Q5YJC2

- GSK3B_SPECI

UniProt

Q5YJC2 - GSK3B_SPECI

Protein

Glycogen synthase kinase-3 beta

Gene

GSK3B

Organism
Spermophilus citellus (European suslik) (Citellus citellus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 69 (01 Oct 2014)
      Sequence version 1 (23 Nov 2004)
      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), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity By similarity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ upon T-cell activation. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity By similarity.By similarity

    Catalytic activityi

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

    Enzyme regulationi

    Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 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 sitei85 – 851ATPPROSITE-ProRule annotation
    Active sitei181 – 1811Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi62 – 709ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. kinase activity Source: UniProtKB
    3. protein serine/threonine kinase activity Source: UniProtKB
    4. tau-protein kinase activity Source: UniProtKB

    GO - Biological processi

    1. cellular response to interleukin-3 Source: UniProtKB
    2. circadian rhythm Source: UniProtKB
    3. epithelial to mesenchymal transition Source: UniProtKB
    4. extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
    5. glycogen metabolic process Source: UniProtKB-KW
    6. negative regulation of NFAT protein import into nucleus Source: UniProtKB
    7. negative regulation of signal transduction Source: UniProtKB-KW
    8. nervous system development Source: UniProtKB-KW
    9. peptidyl-serine phosphorylation Source: UniProtKB
    10. positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
    11. positive regulation of protein binding Source: UniProtKB
    12. protein phosphorylation Source: UniProtKB
    13. regulation of microtubule-based process Source: UniProtKB
    14. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Biological rhythms, Carbohydrate metabolism, Differentiation, Glycogen metabolism, Neurogenesis, Wnt signaling pathway

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glycogen synthase kinase-3 beta (EC:2.7.11.26)
    Short name:
    GSK-3 beta
    Alternative name(s):
    Serine/threonine-protein kinase GSK3B (EC:2.7.11.1)
    Gene namesi
    Name:GSK3B
    OrganismiSpermophilus citellus (European suslik) (Citellus citellus)
    Taxonomic identifieri9997 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiSciuridaeXerinaeMarmotiniSpermophilus

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Cell membrane By similarity
    Note: The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. membrane Source: UniProtKB
    3. nucleus Source: UniProtKB
    4. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 420420Glycogen synthase kinase-3 betaPRO_0000250495Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei9 – 91Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3By similarity
    Modified residuei216 – 2161PhosphotyrosineBy similarity
    Modified residuei389 – 3891PhosphoserineBy similarity
    Modified residuei390 – 3901PhosphothreonineBy similarity

    Post-translational modificationi

    Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 and RPS6KA3 protein kinases phosphorylate and desactivate GSK3B, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-216 By similarity.By similarity
    Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity.By similarity

    Keywords - PTMi

    ADP-ribosylation, Phosphoprotein

    Interactioni

    Subunit structurei

    Monomer By similarity. Interacts with ARRB2, AXIN1, CABYR, DISC1, MMP2, MUC1, NIN, PRUNE, SGK3 and ZBED3. Interacts with and phosphorylates SNAI1 By similarity. Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. Interacts with the CLOCK-ARNTL/BMAL1 heterodimer. Interacts with the ARNTL/BMAL1 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ5YJC2.
    SMRiQ5YJC2. Positions 23-386.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini56 – 340285Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    HOVERGENiHBG014652.

    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.

    Q5YJC2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR    50
    PQEVSYTDTK VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI 100
    MRKLDHCNIV RLRYFFYSSG EKKDVVYLNL VLDYVPETVY RVARHYSRAK 150
    QTLPVIYVKL YMYQLFRSLA YIHSFGICHR DIKPQNLLLD PDTAVLKLCD 200
    FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV WSAGCVLAEL 250
    LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP 300
    WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL 350
    PNGRDTPALF NFTTQELSSN PPLATILIPP HARIQAAAST PTNATAASDA 400
    NAGDRGQTNN AAFASASNST 420
    Length:420
    Mass (Da):46,744
    Last modified:November 23, 2004 - v1
    Checksum:i5F5243CA7D9EA549
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY392021 mRNA. Translation: AAS59774.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY392021 mRNA. Translation: AAS59774.1 .

    3D structure databases

    ProteinModelPortali Q5YJC2.
    SMRi Q5YJC2. Positions 23-386.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    HOVERGENi HBG014652.

    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 of Spermophilus citellus glycogen synthase kinase 3 beta."
      Stieler J.T., Strijkstra A.M.
      Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].

    Entry informationi

    Entry nameiGSK3B_SPECI
    AccessioniPrimary (citable) accession number: Q5YJC2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 3, 2006
    Last sequence update: November 23, 2004
    Last modified: October 1, 2014
    This is version 69 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3