Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P49841 (GSK3B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 182. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length420 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. 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 and diabetes. 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. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. 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. Ref.6 Ref.7 Ref.10 Ref.12 Ref.16 Ref.18 Ref.19 Ref.21 Ref.23 Ref.25 Ref.29 Ref.32 Ref.34 Ref.41 Ref.45

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 and RPS6KA3; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium. Ref.9 Ref.35 Ref.37 Ref.45

Subunit structure

Monomer. Interacts with ARRB2, DISC1 and ZBED3 By similarity. Interacts with CABYR, MMP2, MUC1, NIN and PRUNE Interacts with AXIN1; the interaction mediates hyperphosphorylation of CTNNB1 leading to its ubiquitination and destruction. Interacts with and phosphorylates SNAI1. Interacts with DNM1L (via a C-terminal domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B By similarity. Interacts with SGK3. Interacts with DAB2IP (via C2 domain); the interaction stimulates GSK3B kinase activation. Interacts (via C2 domain) with PPP2CA. Interacts with the CLOCK-ARNTL/BMAL1 heterodimer. Interacts with the ARNTL/BMAL1. Ref.11 Ref.12 Ref.14 Ref.17 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24 Ref.28 Ref.29 Ref.33 Ref.45

Subcellular location

Cytoplasm. Nucleus. Cell membrane. 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. Ref.19 Ref.34 Ref.40

Tissue specificity

Expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. Colocalizes with EIF2AK2/PKR and TAU in the Alzheimer disease (AD) brain. Ref.40

Post-translational modification

Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3B, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-216. Ref.8 Ref.17 Ref.23 Ref.34 Ref.40 Ref.45

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

Miscellaneous

Higher expression and activity of GSK3B are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes (Ref.15). Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes (Ref.37).

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
   Coding sequence diversityAlternative splicing
   DiseaseAlzheimer disease
Diabetes mellitus
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Signal transduction inhibitor
Transferase
   PTMADP-ribosylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processER overload response

Inferred from direct assay PubMed 14744935. Source: MGI

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

canonical Wnt signaling pathway

Inferred by curator PubMed 9601641. Source: UniProtKB

canonical Wnt signaling pathway involved in positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from electronic annotation. Source: Ensembl

cellular response to interleukin-3

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

epithelial to mesenchymal transition

Inferred from mutant phenotype Ref.19. Source: UniProtKB

establishment of cell polarity

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from sequence or structural similarity. Source: UniProtKB

fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

glycogen metabolic process

Inferred from direct assay PubMed 8638126. Source: BHF-UCL

hippocampus development

Inferred from mutant phenotype PubMed 19581563. Source: BHF-UCL

hypermethylation of CpG island

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

intracellular signal transduction

Inferred from direct assay PubMed 14749367. Source: MGI

myoblast fusion

Inferred from electronic annotation. Source: Ensembl

negative regulation of MAP kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of NFAT protein import into nucleus

Inferred from mutant phenotype Ref.10. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay PubMed 14744935. Source: MGI

negative regulation of canonical Wnt signaling pathway

Traceable author statement Ref.37. Source: UniProtKB

negative regulation of cardiac muscle hypertrophy

Inferred from electronic annotation. Source: Ensembl

negative regulation of dendrite morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of glycogen (starch) synthase activity

Traceable author statement Ref.37. Source: UniProtKB

negative regulation of glycogen biosynthetic process

Traceable author statement Ref.37. Source: UniProtKB

negative regulation of protein binding

Inferred from direct assay PubMed 16890161. Source: BHF-UCL

negative regulation of protein complex assembly

Inferred from mutant phenotype PubMed 16188939. Source: BHF-UCL

negative regulation of type B pancreatic cell development

Traceable author statement Ref.37. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 8638126. Source: BHF-UCL

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of Rac GTPase activity

Inferred from mutant phenotype PubMed 18156211. Source: BHF-UCL

positive regulation of cell-matrix adhesion

Inferred from mutant phenotype PubMed 18156211. Source: BHF-UCL

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

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein catabolic process

Inferred by curator PubMed 16188939. Source: BHF-UCL

positive regulation of protein complex assembly

Inferred from direct assay PubMed 8638126. Source: BHF-UCL

positive regulation of protein export from nucleus

Inferred from direct assay PubMed 14744935. Source: MGI

positive regulation of stem cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein export from nucleus

Inferred from electronic annotation. Source: Ensembl

protein localization to microtubule

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.34. Source: UniProtKB

re-entry into mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

regulation of gene expression by genetic imprinting

Inferred from electronic annotation. Source: Ensembl

regulation of microtubule-based process

Inferred from mutant phenotype Ref.34. Source: UniProtKB

regulation of neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to lithium ion

Inferred from electronic annotation. Source: Ensembl

superior temporal gyrus development

Inferred from mutant phenotype PubMed 19581563. Source: BHF-UCL

   Cellular_componentbeta-catenin destruction complex

Inferred from direct assay PubMed 16188939PubMed 9601641. Source: UniProtKB

centrosome

Inferred from direct assay PubMed 21399614. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.19Ref.34. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

dendritic shaft

Inferred from electronic annotation. Source: Ensembl

dendritic spine

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from electronic annotation. Source: Ensembl

membrane raft

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.19. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay Ref.34. Source: UniProtKB

ribonucleoprotein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

NF-kappaB binding

Inferred from physical interaction PubMed 15465828. Source: UniProtKB

RNA polymerase II transcription factor binding

Inferred from physical interaction PubMed 20864106. Source: UniProtKB

beta-catenin binding

Inferred from physical interaction PubMed 8638126. Source: BHF-UCL

kinase activity

Inferred from direct assay Ref.19. Source: UniProtKB

p53 binding

Inferred from direct assay PubMed 14744935. Source: MGI

protein binding

Inferred from physical interaction Ref.19PubMed 9601641Ref.11PubMed 98401153. Source: UniProtKB

protein kinase A catalytic subunit binding

Inferred from physical interaction PubMed 11035810. Source: BHF-UCL

protein kinase binding

Inferred from physical interaction Ref.25. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.25Ref.10. Source: UniProtKB

tau-protein kinase activity

Inferred from direct assay Ref.18. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 21118991. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49841-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P49841-2)

The sequence of this isoform differs from the canonical sequence as follows:
     303-303: K → KDSSGTGHFTSGVR
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 420420Glycogen synthase kinase-3 beta
PRO_0000085980

Regions

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

Sites

Active site1811Proton acceptor
Binding site851ATP By similarity

Amino acid modifications

Modified residue91Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3 Ref.8 Ref.17 Ref.23 Ref.34
Modified residue2161Phosphotyrosine Ref.45
Modified residue3891Phosphoserine By similarity
Modified residue3901Phosphothreonine Ref.27
Modified residue4021Phosphothreonine Ref.26

Natural variations

Alternative sequence3031K → KDSSGTGHFTSGVR in isoform 2.
VSP_004790

Experimental info

Mutagenesis91S → A: Loss of phosphorylation; No inhibition of activity and constitutively active. Ref.1
Mutagenesis961R → A: Prevents the phosphorylation of phosphate-primed glycogen synthase. Ref.16
Mutagenesis1281L → A: Abolishes activity toward AXIN1. Ref.16
Sequence conflict281V → G in AAD48517. Ref.4
Sequence conflict3501L → H in AAA66475. Ref.1

Secondary structure

.................................................................... 420
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 2, 2002. Version 2.
Checksum: 4ACC24D00CDBB9C3

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 
EKKDEVYLNL 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 NTGDRGQTNN AASASASNST 

« Hide

Isoform 2 [UniParc].

Checksum: 540F853E1603A080
Show »

FASTA43348,034

References

« Hide 'large scale' references
[1]"Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation."
Stambolic V., Woodgett J.R.
Biochem. J. 303:701-704(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF SER-9.
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] (ISOFORMS 1 AND 2).
Tissue: Eye and Placenta.
[4]"Molecular cloning and characterization of the human glycogen synthase kinase-3beta promoter."
Lau K.F., Miller C.C.J., Anderton B.H., Shaw P.C.
Genomics 60:121-128(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[5]"Radiation hybrid mapping of genes in the lithium-sensitive wnt signaling pathway."
Rhoads A.R., Karkera J.D., Detera-Wadleigh S.D.
Mol. Psychiatry 4:437-442(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 185-202.
[6]"Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity."
Boyle W.J., Smeal T., Defize L.H., Angel P., Woodgett J.R., Karin M., Hunter T.
Cell 64:573-584(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF JUN.
[7]"Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B."
Welsh G.I., Proud C.G.
Biochem. J. 294:625-629(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF EIF2BE/EIF2B5.
[8]"Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling."
Sutherland C., Leighton I.A., Cohen P.
Biochem. J. 296:15-19(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-9.
[9]"Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B."
Cross D.A., Alessi D.R., Cohen P., Andjelkovich M., Hemmings B.A.
Nature 378:785-789(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION BY AKT1.
[10]"Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3."
Beals C.R., Sheridan C.M., Turck C.W., Gardner P., Crabtree G.R.
Science 275:1930-1934(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NFATC1/NFATC.
[11]"Human dynamin-like protein interacts with the glycogen synthase kinase 3beta."
Hong Y.-R., Chen C.-H., Cheng D.-S., Howng S.-L., Chow C.-C.
Biochem. Biophys. Res. Commun. 249:697-703(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DNM1L.
Tissue: Liver.
[12]"Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin."
Li Y., Bharti A., Chen D., Gong J., Kufe D.
Mol. Cell. Biol. 18:7216-7224(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MUC1, FUNCTION.
[13]"Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase."
Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.
Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[14]"Cloning and characterization of a novel human ninein protein that interacts with the glycogen synthase kinase 3beta."
Hong Y.-R., Chen C.-H., Chang J.-H., Wang S.-K., Sy W.-D., Chou C.-K., Howng S.-L.
Biochim. Biophys. Acta 1492:513-516(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NIN.
[15]"Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes."
Nikoulina S.E., Ciaraldi T.P., Mudaliar S., Mohideen P., Carter L., Henry R.R.
Diabetes 49:263-271(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH DIABETES MELLITUS.
[16]"A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation."
Frame S., Cohen P., Biondi R.M.
Mol. Cell 7:1321-1327(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ARG-96 AND LEU-128.
[17]"Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction."
Dai F., Yu L., He H., Chen Y., Yu J., Yang Y., Xu Y., Ling W., Zhao S.
Biochem. Biophys. Res. Commun. 293:1191-1196(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-9 BY SGK3, INTERACTION WITH SGK3.
[18]"Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta (GSK3beta) plays a critical role in regulating tau's ability to bind and stabilize microtubules."
Cho J.H., Johnson G.V.
J. Neurochem. 88:349-358(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MAPT/TAU.
[19]"Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition."
Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C.
Nat. Cell Biol. 6:931-940(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SNAI1, SUBCELLULAR LOCATION.
[20]"Characterization of two non-testis-specific CABYR variants that bind to GSK3beta with a proline-rich extensin-like domain."
Hsu H.-C., Lee Y.-L., Cheng T.-S., Howng S.-L., Chang L.-K., Lu P.-J., Hong Y.-R.
Biochem. Biophys. Res. Commun. 329:1108-1117(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CABYR.
[21]"Wnt-dependent regulation of the E-cadherin repressor snail."
Yook J.I., Li X.Y., Ota I., Fearon E.R., Weiss S.J.
J. Biol. Chem. 280:11740-11748(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SNAI1.
[22]"Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions."
Kobayashi T., Hino S., Oue N., Asahara T., Zollo M., Yasui W., Kikuchi A.
Mol. Cell. Biol. 26:898-911(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRUNE.
[23]"Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock."
Yin L., Wang J., Klein P.S., Lazar M.A.
Science 311:1002-1005(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-9.
[24]"Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex."
Luo W., Peterson A., Garcia B.A., Coombs G., Kofahl B., Heinrich R., Shabanowitz J., Hunt D.F., Yost H.J., Virshup D.M.
EMBO J. 26:1511-1521(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AXIN1.
[25]"Importance of autophosphorylation at Ser186 in the A-loop of salt inducible kinase 1 for its sustained kinase activity."
Hashimoto Y.K., Satoh T., Okamoto M., Takemori H.
J. Cell. Biochem. 104:1724-1739(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF SIK1.
[26]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-402, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[28]"Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 mediated proteolysis in cardiomyoblasts."
Kandasamy A.D., Schulz R.
Cardiovasc. Res. 83:698-706(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MMP2.
[29]"A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and degradation."
Spengler M.L., Kuropatwinski K.K., Schumer M., Antoch M.P.
Cell Cycle 8:4138-4146(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CLOCK-ARNTL/BMAL1.
[30]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[32]"Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing."
Heyd F., Lynch K.W.
Mol. Cell 40:126-137(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[33]"Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis."
Xie D., Gore C., Liu J., Pong R.C., Mason R., Hao G., Long M., Kabbani W., Yu L., Zhang H., Chen H., Sun X., Boothman D.A., Min W., Hsieh J.T.
Proc. Natl. Acad. Sci. U.S.A. 107:2485-2490(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2IP AND PPP2CA.
[34]"ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells."
Zaoui K., Benseddik K., Daou P., Salaun D., Badache A.
Proc. Natl. Acad. Sci. U.S.A. 107:18517-18522(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-9.
[35]"Glycogen synthase kinase-3: properties, functions, and regulation."
Ali A., Hoeflich K.P., Woodgett J.R.
Chem. Rev. 101:2527-2540(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, ENZYME REGULATION.
[36]"The role of GSK3 in glucose homeostasis and the development of insulin resistance."
Lee J., Kim M.S.
Diabetes Res. Clin. Pract. 77:S49-S57(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[37]"Glycogen synthase kinase 3: more than a namesake."
Rayasam G.V., Tulasi V.K., Sodhi R., Davis J.A., Ray A.
Br. J. Pharmacol. 156:885-898(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION, ENZYME REGULATION.
[38]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[39]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[40]"Modulation of tau phosphorylation by the kinase PKR: implications in Alzheimer's disease."
Bose A., Mouton-Liger F., Paquet C., Mazot P., Vigny M., Gray F., Hugon J.
Brain Pathol. 21:189-200(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION.
[41]"Glycogen synthase kinase 3? (GSK3?) modulates antiviral activity of zinc-finger antiviral protein (ZAP)."
Sun L., Lv F., Guo X., Gao G.
J. Biol. Chem. 287:22882-22888(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[42]"ARTD10 substrate identification on protein microarrays: regulation of GSK3beta by mono-ADP-ribosylation."
Feijs K.L., Kleine H., Braczynski A., Forst A.H., Herzog N., Verheugd P., Linzen U., Kremmer E., Luscher B.
Cell Commun. Signal. 11:5-5(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ADP-RIBOSYLATION BY PARP10.
[43]"Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition."
Dajani R., Fraser E., Roe S.M., Young N., Good V., Dale T.C., Pearl L.H.
Cell 105:721-732(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 35-386.
[44]"The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation."
Bax B., Carter P.S., Lewis C., Guy A.R., Bridges A., Tanner R., Pettman G., Mannix C., Culbert A.A., Brown M.J.B., Smith D.G., Reith A.D.
Structure 9:1143-1152(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 27-393 OF PHOSPHORYLATED GSK3B.
[45]"Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex."
Dajani R., Fraser E., Roe S.M., Yeo M., Good V.M., Thompson V., Dale T.C., Pearl L.H.
EMBO J. 22:494-501(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 35-384 IN COMPLEX WITH AXIN1, INTERACTION WITH AXIN1 AND FRAT1, FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT TYR-216.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L33801 mRNA. Translation: AAA66475.1.
CH471052 Genomic DNA. Translation: EAW79533.1.
CH471052 Genomic DNA. Translation: EAW79536.1.
BC000251 mRNA. Translation: AAH00251.1.
BC012760 mRNA. Translation: AAH12760.1.
AF074333 Genomic DNA. Translation: AAD48517.1.
AF098789 Genomic DNA. Translation: AAC69340.1.
CCDSCCDS2996.1. [P49841-2]
CCDS54628.1. [P49841-1]
PIRS53324.
RefSeqNP_001139628.1. NM_001146156.1. [P49841-1]
NP_002084.2. NM_002093.3. [P49841-2]
UniGeneHs.445733.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GNGX-ray2.60A/B27-393[»]
1H8FX-ray2.80A/B35-386[»]
1I09X-ray2.70A/B1-420[»]
1J1BX-ray1.80A/B1-420[»]
1J1CX-ray2.10A/B1-420[»]
1O6KX-ray1.70C3-12[»]
1O6LX-ray1.60C3-12[»]
1O9UX-ray2.40A35-384[»]
1PYXX-ray2.40A/B1-420[»]
1Q3DX-ray2.20A/B2-420[»]
1Q3WX-ray2.30A/B2-420[»]
1Q41X-ray2.10A/B2-420[»]
1Q4LX-ray2.77A/B2-420[»]
1Q5KX-ray1.94A/B7-420[»]
1R0EX-ray2.25A/B35-420[»]
1UV5X-ray2.80A35-384[»]
2JDOX-ray1.80C3-12[»]
2JDRX-ray2.30C3-12[»]
2JLDX-ray2.35A/B1-420[»]
2O5KX-ray3.20A29-393[»]
2OW3X-ray2.80A/B35-386[»]
2UW9X-ray2.10C3-12[»]
2X39X-ray1.93C3-12[»]
2XH5X-ray2.72C3-12[»]
3CQUX-ray2.20C3-12[»]
3CQWX-ray2.00C3-12[»]
3DU8X-ray2.20A/B1-420[»]
3E87X-ray2.30C/D3-12[»]
3E88X-ray2.50C/D3-12[»]
3E8DX-ray2.70C/D3-12[»]
3F7ZX-ray2.40A/B35-383[»]
3F88X-ray2.60A/B35-383[»]
3GB2X-ray2.40A34-383[»]
3I4BX-ray2.30A/B7-420[»]
3L1SX-ray2.90A/B7-420[»]
3M1SX-ray3.13A/B1-420[»]
3MV5X-ray2.47C3-12[»]
3OW4X-ray2.60C/D3-12[»]
3PUPX-ray2.99A/B1-420[»]
3Q3BX-ray2.70A/B2-420[»]
3QKKX-ray2.30C3-12[»]
3SAYX-ray2.23A/B1-420[»]
3SD0X-ray2.70A/B35-384[»]
3ZDIX-ray2.64A35-384[»]
3ZRKX-ray2.37A/B23-393[»]
3ZRLX-ray2.48A/B23-393[»]
3ZRMX-ray2.49A/B23-393[»]
4ACCX-ray2.21A/B1-420[»]
4ACDX-ray2.60A/B1-420[»]
4ACGX-ray2.60A/B1-420[»]
4ACHX-ray2.60A/B1-420[»]
4AFJX-ray1.98A/B27-393[»]
4B7TX-ray2.77A35-384[»]
4DITX-ray2.60A27-393[»]
4EKKX-ray2.80C/D3-12[»]
4IQ6X-ray3.12A/B1-420[»]
4J1RX-ray2.70A/B/C/D1-420[»]
4J71X-ray2.31A/B1-420[»]
4NM0X-ray2.50A1-383[»]
4NM3X-ray2.10A1-383[»]
4NM5X-ray2.30A13-383[»]
4NM7X-ray2.30A13-383[»]
DisProtDP00385.
ProteinModelPortalP49841.
SMRP49841. Positions 6-386.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109187. 299 interactions.
DIPDIP-878N.
IntActP49841. 174 interactions.
MINTMINT-105006.
STRING9606.ENSP00000324806.

Chemistry

BindingDBP49841.
ChEMBLCHEMBL2095188.
DrugBankDB01356. Lithium.
GuidetoPHARMACOLOGY2030.

PTM databases

PhosphoSiteP49841.

Polymorphism databases

DMDM20455502.

Proteomic databases

MaxQBP49841.
PaxDbP49841.
PRIDEP49841.

Protocols and materials databases

DNASU2932.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264235; ENSP00000264235; ENSG00000082701. [P49841-1]
ENST00000316626; ENSP00000324806; ENSG00000082701. [P49841-2]
GeneID2932.
KEGGhsa:2932.
UCSCuc003edn.3. human. [P49841-2]
uc003edo.3. human. [P49841-1]

Organism-specific databases

CTD2932.
GeneCardsGC03M119540.
HGNCHGNC:4617. GSK3B.
HPACAB016263.
HPA028017.
MIM605004. gene.
neXtProtNX_P49841.
PharmGKBPA29009.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233017.
HOVERGENHBG014652.
KOK03083.
OMANAGERVQ.
OrthoDBEOG7TF78V.
PhylomeDBP49841.
TreeFamTF101104.

Enzyme and pathway databases

BRENDA2.7.11.26. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
REACT_6900. Immune System.
SignaLinkP49841.

Gene expression databases

ArrayExpressP49841.
BgeeP49841.
CleanExHS_GSK3B.
GenevestigatorP49841.

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...

Other

ChiTaRSGSK3B. human.
EvolutionaryTraceP49841.
GeneWikiGSK3B.
GenomeRNAi2932.
NextBio11619.
PROP49841.
SOURCESearch...

Entry information

Entry nameGSK3B_HUMAN
AccessionPrimary (citable) accession number: P49841
Secondary accession number(s): D3DN89, Q9BWH3, Q9UL47
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 2, 2002
Last modified: July 9, 2014
This is version 182 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM