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Protein

Glycogen synthase kinase-3 beta

Gene

GSK3B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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. 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. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509).16 Publications

Miscellaneous

Higher expression and activity of GSK3B are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes (PubMed:10868943). Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes (PubMed:19366350).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei85ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei181Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi62 – 70ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Signal transduction inhibitor, Transferase
Biological processBiological rhythms, Carbohydrate metabolism, Differentiation, Glycogen metabolism, Neurogenesis, Wnt signaling pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.11.26 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-198323 AKT phosphorylates targets in the cytosol
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-399956 CRMPs in Sema3A signaling
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5250924 B-WICH complex positively regulates rRNA expression
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-HSA-8939902 Regulation of RUNX2 expression and activity

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P49841

SIGNOR Signaling Network Open Resource

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SIGNORi
P49841

Protein family/group databases

UniLectin database of carbohydrate-binding proteins

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UniLectini
P49841

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:GSK3B
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 3

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000082701.14

Human Gene Nomenclature Database

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HGNCi
HGNC:4617 GSK3B

Online Mendelian Inheritance in Man (OMIM)

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MIMi
605004 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P49841

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi9S → A: Loss of phosphorylation; No inhibition of activity and constitutively active. 1 Publication1
Mutagenesisi96R → A: Prevents the phosphorylation of phosphate-primed glycogen synthase. 1 Publication1
Mutagenesisi128L → A: Abolishes activity toward AXIN1. 1 Publication1

Keywords - Diseasei

Alzheimer disease, Diabetes mellitus

Organism-specific databases

DisGeNET

More...
DisGeNETi
2932

Open Targets

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OpenTargetsi
ENSG00000082701

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA29009

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL262

Drug and drug target database

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DrugBanki
DB08073 (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE
DB07859 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE
DB04014 Alsterpaullone
DB01793 I-5
DB02052 Indirubin-3'-Monoxime
DB07947 ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE
DB01356 Lithium
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB02010 Staurosporine

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2030

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
GSK3B

Domain mapping of disease mutations (DMDM)

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DMDMi
20455502

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000859801 – 420Glycogen synthase kinase-3 betaAdd BLAST420

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei9Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK36 Publications1
Modified residuei216Phosphotyrosine2 Publications1
Modified residuei389PhosphoserineBy similarity1
Modified residuei390PhosphothreonineCombined sources1
Modified residuei402PhosphothreonineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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 (PubMed:25169422). Inactivated by phosphorylation at Ser-9 (Probable).1 Publication7 Publications
Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity.

Keywords - PTMi

ADP-ribosylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P49841

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P49841

PeptideAtlas

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PeptideAtlasi
P49841

PRoteomics IDEntifications database

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PRIDEi
P49841

ProteomicsDB human proteome resource

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ProteomicsDBi
56151
56152 [P49841-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P49841

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P49841

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000082701 Expressed in 230 organ(s), highest expression level in forebrain

CleanEx database of gene expression profiles

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CleanExi
HS_GSK3B

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P49841 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P49841 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB016263
HPA028017

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer. Interacts with ARRB2, DISC1 and ZBED3 (By similarity). Interacts with CABYR, MMP2, MUC1, NIN and PRUNE1. 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. Interacts with CTNND2 (PubMed:19706605). Interacts with NCYM (PubMed:24391509). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (PubMed:27484798, PubMed:20007971, PubMed:25920809). Interacts with GSK3B; induces GSK3B-mediated phosphorylation of GSKIP (PubMed:16981698). Interacts with GID8 (PubMed:28829046).By similarity21 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
109187, 302 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-109 Beta-catenin destruction core complex, variant 1
CPX-439 Beta-catenin destruction core complex, variant 3
CPX-440 Beta-catenin destruction core complex, variant 4
CPX-459 Nuclear export complex FRAT1-GSK3B
CPX-462 Nuclear export complex FRAT2-GSK3B
CPX-99 Beta-catenin destruction core complex, variant 2

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P49841

Database of interacting proteins

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DIPi
DIP-878N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P49841

Protein interaction database and analysis system

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IntActi
P49841, 252 interactors

Molecular INTeraction database

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MINTi
P49841

STRING: functional protein association networks

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STRINGi
9606.ENSP00000324806

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P49841

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1420
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Database of protein disorder

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DisProti
DP00385

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P49841

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P49841

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P49841

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini56 – 340Protein kinasePROSITE-ProRule annotationAdd BLAST285

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0658 Eukaryota
COG0515 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00520000055635

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000233017

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG014652

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P49841

KEGG Orthology (KO)

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KOi
K03083

Identification of Orthologs from Complete Genome Data

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OMAi
YSNGDKK

Database of Orthologous Groups

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OrthoDBi
EOG091G099S

Database for complete collections of gene phylogenies

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PhylomeDBi
P49841

TreeFam database of animal gene trees

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TreeFami
TF101104

Family and domain databases

Conserved Domains Database

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CDDi
cd14137 STKc_GSK3, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR033573 GSK3B
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR039192 STKc_GSK3

The PANTHER Classification System

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PANTHERi
PTHR24057:SF8 PTHR24057:SF8, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00069 Pkinase, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P49841-1) [UniParc]FASTAAdd to basket
Also known as: GSK-3beta1

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.

« Hide
        10         20         30         40         50
MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR
60 70 80 90 100
PQEVSYTDTK VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI
110 120 130 140 150
MRKLDHCNIV RLRYFFYSSG EKKDEVYLNL VLDYVPETVY RVARHYSRAK
160 170 180 190 200
QTLPVIYVKL YMYQLFRSLA YIHSFGICHR DIKPQNLLLD PDTAVLKLCD
210 220 230 240 250
FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV WSAGCVLAEL
260 270 280 290 300
LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP
310 320 330 340 350
WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL
360 370 380 390 400
PNGRDTPALF NFTTQELSSN PPLATILIPP HARIQAAAST PTNATAASDA
410 420
NTGDRGQTNN AASASASNST
Length:420
Mass (Da):46,744
Last modified:May 2, 2002 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i4ACC24D00CDBB9C3
GO
Isoform 2 (identifier: P49841-2) [UniParc]FASTAAdd to basket
Also known as: GSK-3beta2, neuron-specific

The sequence of this isoform differs from the canonical sequence as follows:
     303-303: K → KDSSGTGHFTSGVR

Note: May play a specific role in axon growth and neurite outgrowth. Reduced binding to AXIN1, reduced ability to phosphorylate MAPT/TAU.1 Publication
Show »
Length:433
Mass (Da):48,034
Checksum:i540F853E1603A080
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti28V → G in AAD48517 (PubMed:10486203).Curated1
Sequence conflicti350L → H in AAA66475 (PubMed:7980435).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_004790303K → KDSSGTGHFTSGVR in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
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

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS2996.1 [P49841-2]
CCDS54628.1 [P49841-1]

Protein sequence database of the Protein Information Resource

More...
PIRi
S53324

NCBI Reference Sequences

More...
RefSeqi
NP_001139628.1, NM_001146156.1 [P49841-1]
NP_002084.2, NM_002093.3 [P49841-2]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.445733

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000264235; ENSP00000264235; ENSG00000082701 [P49841-1]
ENST00000316626; ENSP00000324806; ENSG00000082701 [P49841-2]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
2932

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:2932

UCSC genome browser

More...
UCSCi
uc003edn.4 human [P49841-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS2996.1 [P49841-2]
CCDS54628.1 [P49841-1]
PIRiS53324
RefSeqiNP_001139628.1, NM_001146156.1 [P49841-1]
NP_002084.2, NM_002093.3 [P49841-2]
UniGeneiHs.445733

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB 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[»]
4PTCX-ray2.71A/B1-420[»]
4PTEX-ray2.03A/B1-420[»]
4PTGX-ray2.36A/B1-420[»]
5F94X-ray2.51A/B36-385[»]
5F95X-ray2.52A/B36-385[»]
5HLNX-ray3.10A/B1-420[»]
5HLPX-ray2.45A/B1-420[»]
5K5NX-ray2.20A/B28-384[»]
5KPKX-ray2.40A/B1-420[»]
5KPLX-ray2.60A/B1-420[»]
5KPMX-ray2.69A/B1-420[»]
5OY4X-ray3.20A/B1-420[»]
5T31X-ray2.85A/B1-420[»]
6B8JX-ray2.60A1-420[»]
6GN1X-ray2.60A/B27-393[»]
DisProtiDP00385
ProteinModelPortaliP49841
SMRiP49841
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109187, 302 interactors
ComplexPortaliCPX-109 Beta-catenin destruction core complex, variant 1
CPX-439 Beta-catenin destruction core complex, variant 3
CPX-440 Beta-catenin destruction core complex, variant 4
CPX-459 Nuclear export complex FRAT1-GSK3B
CPX-462 Nuclear export complex FRAT2-GSK3B
CPX-99 Beta-catenin destruction core complex, variant 2
CORUMiP49841
DIPiDIP-878N
ELMiP49841
IntActiP49841, 252 interactors
MINTiP49841
STRINGi9606.ENSP00000324806

Chemistry databases

BindingDBiP49841
ChEMBLiCHEMBL262
DrugBankiDB08073 (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE
DB07859 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE
DB04014 Alsterpaullone
DB01793 I-5
DB02052 Indirubin-3'-Monoxime
DB07947 ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE
DB01356 Lithium
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester
DB02010 Staurosporine
GuidetoPHARMACOLOGYi2030

Protein family/group databases

UniLectiniP49841

PTM databases

iPTMnetiP49841
PhosphoSitePlusiP49841

Polymorphism and mutation databases

BioMutaiGSK3B
DMDMi20455502

Proteomic databases

EPDiP49841
PaxDbiP49841
PeptideAtlasiP49841
PRIDEiP49841
ProteomicsDBi56151
56152 [P49841-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
2932
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264235; ENSP00000264235; ENSG00000082701 [P49841-1]
ENST00000316626; ENSP00000324806; ENSG00000082701 [P49841-2]
GeneIDi2932
KEGGihsa:2932
UCSCiuc003edn.4 human [P49841-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
2932
DisGeNETi2932
EuPathDBiHostDB:ENSG00000082701.14

GeneCards: human genes, protein and diseases

More...
GeneCardsi
GSK3B
HGNCiHGNC:4617 GSK3B
HPAiCAB016263
HPA028017
MIMi605004 gene
neXtProtiNX_P49841
OpenTargetsiENSG00000082701
PharmGKBiPA29009

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0658 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00520000055635
HOGENOMiHOG000233017
HOVERGENiHBG014652
InParanoidiP49841
KOiK03083
OMAiYSNGDKK
OrthoDBiEOG091G099S
PhylomeDBiP49841
TreeFamiTF101104

Enzyme and pathway databases

BRENDAi2.7.11.26 2681
ReactomeiR-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-198323 AKT phosphorylates targets in the cytosol
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-399956 CRMPs in Sema3A signaling
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5250924 B-WICH complex positively regulates rRNA expression
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-HSA-8939902 Regulation of RUNX2 expression and activity
SignaLinkiP49841
SIGNORiP49841

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
GSK3B human
EvolutionaryTraceiP49841

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
GSK3B

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
2932

Protein Ontology

More...
PROi
PR:P49841

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000082701 Expressed in 230 organ(s), highest expression level in forebrain
CleanExiHS_GSK3B
ExpressionAtlasiP49841 baseline and differential
GenevisibleiP49841 HS

Family and domain databases

CDDicd14137 STKc_GSK3, 1 hit
InterProiView protein in InterPro
IPR033573 GSK3B
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR039192 STKc_GSK3
PANTHERiPTHR24057:SF8 PTHR24057:SF8, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiGSK3B_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P49841
Secondary accession number(s): D3DN89, Q9BWH3, Q9UL47
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 2, 2002
Last modified: December 5, 2018
This is version 232 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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