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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-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.

Enzyme 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

  • ATP binding Source: UniProtKB-KW
  • beta-catenin binding Source: BHF-UCL
  • dynein complex binding Source: Ensembl
  • kinase activity Source: UniProtKB
  • NF-kappaB binding Source: UniProtKB
  • p53 binding Source: MGI
  • protease binding Source: ParkinsonsUK-UCL
  • protein kinase A catalytic subunit binding Source: BHF-UCL
  • protein kinase activity Source: ParkinsonsUK-UCL
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: UniProtKB
  • tau-protein kinase activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: BHF-UCL

GO - Biological processi

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.
SignaLinkiP49841.
SIGNORiP49841.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:4617. GSK3B.

Subcellular locationi

  • 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.

GO - Cellular componenti

  • beta-catenin destruction complex Source: UniProtKB
  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • dendritic shaft Source: Ensembl
  • growth cone Source: Ensembl
  • intracellular ribonucleoprotein complex Source: Ensembl
  • mitochondrion Source: GOC
  • neuronal cell body Source: Ensembl
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: Ensembl
  • Wnt signalosome Source: ParkinsonsUK-UCL

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 SGK35 Publications1
Modified residuei216Phosphotyrosine1 Publication1
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-216.6 Publications
Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity.

Keywords - PTMi

ADP-ribosylation, Phosphoprotein

Proteomic databases

EPDiP49841.
PaxDbiP49841.
PeptideAtlasiP49841.
PRIDEiP49841.

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.
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).By similarity15 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • beta-catenin binding Source: BHF-UCL
  • dynein complex binding Source: Ensembl
  • NF-kappaB binding Source: UniProtKB
  • p53 binding Source: MGI
  • protease binding Source: ParkinsonsUK-UCL
  • protein kinase A catalytic subunit binding Source: BHF-UCL
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109187. 285 interactors.
DIPiDIP-878N.
IntActiP49841. 193 interactors.
MINTiMINT-105006.
STRINGi9606.ENSP00000324806.

Chemistry databases

BindingDBiP49841.

Structurei

Secondary structure

1420
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi10 – 12Combined sources3
Beta strandi26 – 30Combined sources5
Beta strandi32 – 34Combined sources3
Beta strandi38 – 48Combined sources11
Beta strandi52 – 64Combined sources13
Beta strandi66 – 75Combined sources10
Turni76 – 78Combined sources3
Beta strandi81 – 88Combined sources8
Beta strandi91 – 93Combined sources3
Helixi96 – 102Combined sources7
Beta strandi112 – 120Combined sources9
Turni121 – 124Combined sources4
Beta strandi125 – 133Combined sources9
Beta strandi136 – 138Combined sources3
Helixi139 – 148Combined sources10
Helixi155 – 173Combined sources19
Turni174 – 176Combined sources3
Helixi184 – 186Combined sources3
Beta strandi187 – 190Combined sources4
Turni191 – 194Combined sources4
Beta strandi195 – 198Combined sources4
Beta strandi209 – 211Combined sources3
Helixi220 – 222Combined sources3
Helixi225 – 228Combined sources4
Helixi237 – 252Combined sources16
Helixi262 – 273Combined sources12
Helixi278 – 284Combined sources7
Helixi286 – 288Combined sources3
Beta strandi289 – 291Combined sources3
Helixi301 – 304Combined sources4
Helixi311 – 320Combined sources10
Helixi325 – 327Combined sources3
Helixi331 – 335Combined sources5
Helixi338 – 344Combined sources7
Beta strandi345 – 347Combined sources3
Helixi364 – 367Combined sources4
Helixi371 – 373Combined sources3
Helixi374 – 377Combined sources4
Turni380 – 383Combined sources4

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[»]
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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR033573. GSK3B.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PANTHERiPTHR24057:SF26. PTHR24057:SF26. 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

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[»]
DisProtiDP00385.
ProteinModelPortaliP49841.
SMRiP49841.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109187. 285 interactors.
DIPiDIP-878N.
IntActiP49841. 193 interactors.
MINTiMINT-105006.
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.

PTM databases

iPTMnetiP49841.
PhosphoSitePlusiP49841.

Polymorphism and mutation databases

BioMutaiGSK3B.
DMDMi20455502.

Proteomic databases

EPDiP49841.
PaxDbiP49841.
PeptideAtlasiP49841.
PRIDEiP49841.

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.
GeneCardsiGSK3B.
HGNCiHGNC:4617. GSK3B.
HPAiCAB016263.
HPA028017.
MIMi605004. gene.
neXtProtiNX_P49841.
OpenTargetsiENSG00000082701.
PharmGKBiPA29009.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0658. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00520000055635.
HOGENOMiHOG000233017.
HOVERGENiHBG014652.
InParanoidiP49841.
KOiK03083.
OMAiELIFGNQ.
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.
SignaLinkiP49841.
SIGNORiP49841.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000082701.
CleanExiHS_GSK3B.
ExpressionAtlasiP49841. baseline and differential.
GenevisibleiP49841. HS.

Family and domain databases

InterProiView protein in InterPro
IPR033573. GSK3B.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PANTHERiPTHR24057:SF26. PTHR24057:SF26. 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: May 10, 2017
This is version 214 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.