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UniProtKB - P49841 (GSK3B_HUMAN)

Protein

Glycogen synthase kinase-3 beta

Gene

GSK3B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), 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

Catalytic activityi

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

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
Binding sitei85ATPPROSITE-ProRule annotation1
Active sitei181Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi62 – 70ATPPROSITE-ProRule annotation9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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

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

Protein family/group databases

UniLectiniP49841

Names & Taxonomyi

Protein namesi
Recommended name:
Glycogen synthase kinase-3 beta (EC:2.7.11.26)
Short name:
GSK-3 beta
Alternative name(s):
Serine/threonine-protein kinase GSK3B (EC:2.7.11.1)
Gene namesi
Name:GSK3B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000082701.14
HGNCiHGNC:4617 GSK3B
MIMi605004 gene
neXtProtiNX_P49841

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

DisGeNETi2932
OpenTargetsiENSG00000082701
PharmGKBiPA29009

Chemistry databases

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

Polymorphism and mutation databases

BioMutaiGSK3B
DMDMi20455502

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859801 – 420Glycogen synthase kinase-3 betaAdd BLAST420

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei9Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK36 Publications1
Modified residuei216Phosphotyrosine2 Publications1
Modified residuei389PhosphoserineBy similarity1
Modified residuei390PhosphothreonineCombined sources1
Modified residuei402PhosphothreonineCombined sources1

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

EPDiP49841
PaxDbiP49841
PeptideAtlasiP49841
PRIDEiP49841
ProteomicsDBi56151
56152 [P49841-2]

PTM databases

iPTMnetiP49841
PhosphoSitePlusiP49841

Expressioni

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

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

Organism-specific databases

HPAiCAB016263
HPA028017

Interactioni

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

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109187, 297 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, 251 interactors
MINTiP49841
STRINGi9606.ENSP00000324806

Chemistry databases

BindingDBiP49841

Structurei

Secondary structure

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

3D structure databases

DisProtiDP00385
ProteinModelPortaliP49841
SMRiP49841
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49841

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 340Protein kinasePROSITE-ProRule annotationAdd BLAST285

Sequence similaritiesi

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

Phylogenomic databases

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

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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 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
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
Sequence conflicti28V → G in AAD48517 (PubMed:10486203).Curated1
Sequence conflicti350L → H in AAA66475 (PubMed:7980435).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004790303K → KDSSGTGHFTSGVR in isoform 2. 1 Publication1

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

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

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:
PDBei
RCSB PDBi
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, 297 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, 251 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

DNASUi2932
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

CTDi2932
DisGeNETi2932
EuPathDBiHostDB:ENSG00000082701.14
GeneCardsiGSK3B
HGNCiHGNC:4617 GSK3B
HPAiCAB016263
HPA028017
MIMi605004 gene
neXtProtiNX_P49841
OpenTargetsiENSG00000082701
PharmGKBiPA29009
GenAtlasiSearch...

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

ChiTaRSiGSK3B human
EvolutionaryTraceiP49841
GeneWikiiGSK3B
GenomeRNAii2932
PROiPR:P49841
SOURCEiSearch...

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
ProtoNetiSearch...

Entry informationi

Entry nameiGSK3B_HUMAN
AccessioniPrimary (citable) accession number: P49841
Secondary accession number(s): D3DN89, Q9BWH3, Q9UL47
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 2, 2002
Last modified: October 10, 2018
This is version 230 of the entry and version 2 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

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