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Q5YJC2

- GSK3B_SPECI

UniProt

Q5YJC2 - GSK3B_SPECI

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Protein

Glycogen synthase kinase-3 beta

Gene

GSK3B

Organism
Spermophilus citellus (European suslik) (Citellus citellus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript 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. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity (By similarity). Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ upon T-cell activation. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity (By similarity).By similarity

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; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei85 – 851ATPPROSITE-ProRule annotation
Active sitei181 – 1811Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi62 – 709ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. kinase activity Source: UniProtKB
  3. protein serine/threonine kinase activity Source: UniProtKB
  4. tau-protein kinase activity Source: UniProtKB

GO - Biological processi

  1. cellular response to interleukin-3 Source: UniProtKB
  2. circadian rhythm Source: UniProtKB
  3. epithelial to mesenchymal transition Source: UniProtKB
  4. extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  5. glycogen metabolic process Source: UniProtKB-KW
  6. negative regulation of NFAT protein import into nucleus Source: UniProtKB
  7. negative regulation of signal transduction Source: UniProtKB-KW
  8. nervous system development Source: UniProtKB-KW
  9. peptidyl-serine phosphorylation Source: UniProtKB
  10. positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
  11. positive regulation of protein binding Source: UniProtKB
  12. protein phosphorylation Source: UniProtKB
  13. regulation of microtubule-based process Source: UniProtKB
  14. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Signal transduction inhibitor, Transferase

Keywords - Biological processi

Biological rhythms, Carbohydrate metabolism, Differentiation, Glycogen metabolism, Neurogenesis, Wnt signaling pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

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
OrganismiSpermophilus citellus (European suslik) (Citellus citellus)
Taxonomic identifieri9997 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiSciuridaeXerinaeMarmotiniSpermophilus

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity. Cell membrane By similarity
Note: The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane (By similarity).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. membrane Source: UniProtKB
  3. nucleus Source: UniProtKB
  4. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 420420Glycogen synthase kinase-3 betaPRO_0000250495Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei9 – 91Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3By similarity
Modified residuei216 – 2161PhosphotyrosineBy similarity
Modified residuei389 – 3891PhosphoserineBy similarity
Modified residuei390 – 3901PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 and RPS6KA3 protein kinases phosphorylate and desactivate GSK3B, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-216 (By similarity).By similarity
Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity.By similarity

Keywords - PTMi

ADP-ribosylation, Phosphoprotein

Interactioni

Subunit structurei

Monomer (By similarity). Interacts with ARRB2, AXIN1, CABYR, DISC1, MMP2, MUC1, NIN, PRUNE, SGK3 and ZBED3. Interacts with and phosphorylates SNAI1 (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. Interacts with the CLOCK-ARNTL/BMAL1 heterodimer. Interacts with the ARNTL/BMAL1 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ5YJC2.
SMRiQ5YJC2. Positions 23-386.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini56 – 340285Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

HOVERGENiHBG014652.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5YJC2-1 [UniParc]FASTAAdd to Basket

« 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 EKKDVVYLNL 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
NAGDRGQTNN AAFASASNST
Length:420
Mass (Da):46,744
Last modified:November 23, 2004 - v1
Checksum:i5F5243CA7D9EA549
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY392021 mRNA. Translation: AAS59774.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY392021 mRNA. Translation: AAS59774.1 .

3D structure databases

ProteinModelPortali Q5YJC2.
SMRi Q5YJC2. Positions 23-386.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOVERGENi HBG014652.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Molecular cloning of Spermophilus citellus glycogen synthase kinase 3 beta."
    Stieler J.T., Strijkstra A.M.
    Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiGSK3B_SPECI
AccessioniPrimary (citable) accession number: Q5YJC2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: November 23, 2004
Last modified: October 29, 2014
This is version 70 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3