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Q5YJC2 (GSK3B_SPECI) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 68. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycogen synthase kinase-3 beta

Short name=GSK-3 beta
EC=2.7.11.26
Alternative name(s):
Serine/threonine-protein kinase GSK3B
EC=2.7.11.1
Gene names
Name:GSK3B
OrganismSpermophilus citellus (European suslik) (Citellus citellus)
Taxonomic identifier9997 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiSciuridaeXerinaeMarmotiniSpermophilus

Protein attributes

Sequence length420 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

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

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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.

Subunit structure

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.

Subcellular location

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.

Post-translational modification

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.

Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processBiological rhythms
Carbohydrate metabolism
Differentiation
Glycogen metabolism
Neurogenesis
Wnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Signal transduction inhibitor
Transferase
   PTMADP-ribosylation
Phosphoprotein
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to interleukin-3

Inferred from sequence or structural similarity. Source: UniProtKB

circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial to mesenchymal transition

Inferred from sequence or structural similarity. Source: UniProtKB

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from sequence or structural similarity. Source: UniProtKB

glycogen metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of NFAT protein import into nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of signal transduction

Inferred from electronic annotation. Source: UniProtKB-KW

nervous system development

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-serine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of microtubule-based process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

tau-protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 420420Glycogen synthase kinase-3 beta
PRO_0000250495

Regions

Domain56 – 340285Protein kinase
Nucleotide binding62 – 709ATP By similarity

Sites

Active site1811Proton acceptor By similarity
Binding site851ATP By similarity

Amino acid modifications

Modified residue91Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3 By similarity
Modified residue2161Phosphotyrosine By similarity
Modified residue3891Phosphoserine By similarity
Modified residue3901Phosphothreonine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q5YJC2 [UniParc].

Last modified November 23, 2004. Version 1.
Checksum: 5F5243CA7D9EA549

FASTA42046,744
        10         20         30         40         50         60 
MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR PQEVSYTDTK 

        70         80         90        100        110        120 
VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG 

       130        140        150        160        170        180 
EKKDVVYLNL VLDYVPETVY RVARHYSRAK QTLPVIYVKL YMYQLFRSLA YIHSFGICHR 

       190        200        210        220        230        240 
DIKPQNLLLD PDTAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV 

       250        260        270        280        290        300 
WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP 

       310        320        330        340        350        360 
WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL PNGRDTPALF 

       370        380        390        400        410        420 
NFTTQELSSN PPLATILIPP HARIQAAAST PTNATAASDA NAGDRGQTNN AAFASASNST 

« Hide

References

[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].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY392021 mRNA. Translation: AAS59774.1.

3D structure databases

ProteinModelPortalQ5YJC2.
SMRQ5YJC2. Positions 23-386.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG014652.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameGSK3B_SPECI
AccessionPrimary (citable) accession number: Q5YJC2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: November 23, 2004
Last modified: June 11, 2014
This is version 68 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families