Glycogen synthase kinase-3 beta

Details

Name
Glycogen synthase kinase-3 beta
Synonyms
  • 2.7.11.26
  • GSK-3 beta
  • Serine/threonine-protein kinase GSK3B
Gene Name
GSK3B
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002121|Glycogen synthase kinase-3 beta
MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTK
VIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSG
EKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHR
DIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDV
WSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHP
WTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALF
NFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST
Number of residues
420
Molecular Weight
46743.865
Theoretical pI
8.97
GO Classification
Functions
ATP binding / beta-catenin binding / kinase activity / NF-kappaB binding / p53 binding / protein kinase A catalytic subunit binding / protein kinase binding / protein serine/threonine kinase activity / RNA polymerase II transcription factor binding / tau-protein kinase activity / ubiquitin protein ligase binding
Processes
axon guidance / canonical Wnt signaling pathway / canonical Wnt signaling pathway involved in positive regulation of apoptotic process / cell migration / cellular response to heat / cellular response to interleukin-3 / circadian rhythm / epidermal growth factor receptor signaling pathway / epithelial to mesenchymal transition / ER overload response / extrinsic apoptotic signaling pathway in absence of ligand / fat cell differentiation / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / glycogen metabolic process / hippocampus development / hypermethylation of CpG island / innate immune response / intracellular signal transduction / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / myoblast fusion / negative regulation of apoptotic process / negative regulation of canonical Wnt signaling pathway / negative regulation of cardiac muscle hypertrophy / negative regulation of glycogen (starch) synthase activity / negative regulation of glycogen biosynthetic process / negative regulation of neuron maturation / negative regulation of neuron projection development / negative regulation of NFAT protein import into nucleus / negative regulation of protein binding / negative regulation of protein complex assembly / negative regulation of protein localization to nucleus / negative regulation of type B pancreatic cell development / neurotrophin TRK receptor signaling pathway / organ morphogenesis / peptidyl-serine phosphorylation / phosphatidylinositol-mediated signaling / positive regulation of axon extension / positive regulation of canonical Wnt signaling pathway / positive regulation of cell-matrix adhesion / positive regulation of GTPase activity / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of peptidyl-serine phosphorylation / positive regulation of peptidyl-threonine phosphorylation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of protein binding / positive regulation of protein catabolic process / positive regulation of protein complex assembly / positive regulation of protein export from nucleus / positive regulation of stem cell differentiation / positive regulation of transcription from RNA polymerase II promoter / protein autophosphorylation / protein export from nucleus / protein localization to microtubule / protein phosphorylation / re-entry into mitotic cell cycle / regulation of cellular response to heat / regulation of gene expression by genetic imprinting / regulation of microtubule-based process / superior temporal gyrus development
Components
beta-catenin destruction complex / centrosome / cytoplasm / cytosol / dendritic shaft / growth cone / neuronal cell body / neuronal postsynaptic density / nucleus / perinuclear region of cytoplasm / plasma membrane / ribonucleoprotein complex
General Function
Ubiquitin protein ligase binding
Specific Function
Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021658|Glycogen synthase kinase-3 beta (GSK3B)
ATGTCAGGGCGGCCCAGAACCACCTCCTTTGCGGAGAGCTGCAAGCCGGTGCAGCAGCCT
TCAGCTTTTGGCAGCATGAAAGTTAGCAGAGACAAGGACGGCAGCAAGGTGACAACAGTG
GTGGCAACTCCTGGGCAGGGTCCAGACAGGCCACAAGAAGTCAGCTATACAGACACTAAA
GTGATTGGAAATGGATCATTTGGTGTGGTATATCAAGCCAAACTTTGTGATTCAGGAGAA
CTGGTCGCCATCAAGAAAGTATTGCAGGACAAGAGATTTAAGAATCGAGAGCTCCAGATC
ATGAGAAAGCTAGATCACTGTAACATAGTCCGATTGCGTTATTTCTTCTACTCCAGTGGT
GAGAAGAAAGATGAGGTCTATCTTAATCTGGTGCTGGACTATGTTCCGGAAACAGTATAC
AGAGTTGCCAGACACTATAGTCGAGCCAAACAGACGCTCCCTGTGATTTATGTCAAGTTG
TATATGTATCAGCTGTTCCGAAGTTTAGCCTATATCCATTCCTTTGGAATCTGCCATCGG
GATATTAAACCGCAGAACCTCTTGTTGGATCCTGATACTGCTGTATTAAAACTCTGTGAC
TTTGGAAGTGCAAAGCAGCTGGTCCGAGGAGAACCCAATGTTTCGTATATCTGTTCTCGG
TACTATAGGGCACCAGAGTTGATCTTTGGAGCCACTGATTATACCTCTAGTATAGATGTA
TGGTCTGCTGGCTGTGTGTTGGCTGAGCTGTTACTAGGACAACCAATATTTCCAGGGGAT
AGTGGTGTGGATCAGTTGGTAGAAATAATCAAGGTCCTGGGAACTCCAACAAGGGAGCAA
ATCAGAGAAATGAACCCAAACTACACAGAATTTAAATTCCCTCAAATTAAGGCACATCCT
TGGACTAAGGTCTTCCGACCCCGAACTCCACCGGAGGCAATTGCACTGTGTAGCCGTCTG
CTGGAGTATACACCAACTGCCCGACTAACACCACTGGAAGCTTGTGCACATTCATTTTTT
GATGAATTACGGGACCCAAATGTCAAACTACCAAATGGGCGAGACACACCTGCACTCTTC
AACTTCACCACTCAAGAACTGTCAAGTAATCCACCTCTGGCTACCATCCTTATTCCTCCT
CATGCTCGGATTCAAGCAGCTGCTTCAACCCCCACAAATGCCACAGCAGCGTCAGATGCT
AATACTGGAGACCGTGGACAGACCAATAATGCTGCTTCTGCATCAGCTTCCAACTCCACC
TGA
Chromosome Location
3
Locus
3q13.3
External Identifiers
ResourceLink
UniProtKB IDP49841
UniProtKB Entry NameGSK3B_HUMAN
GenBank Protein ID529237
GenBank Gene IDL33801
GenAtlas IDGSK3B
HGNC IDHGNC:4617
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01356Lithium cationexperimentalunknowninhibitorDetails
DB017723-[3-(2,3-Dihydroxy-Propylamino)-Phenyl]-4-(5-Fluoro-1-Methyl-1h-Indol-3-Yl)-Pyrrole-2,5-DioneexperimentalunknownDetails
DB01793SB-409513experimentalunknownDetails
DB01950N-(4-Methoxybenzyl)-N'-(5-Nitro-1,3-Thiazol-2-Yl)UreaexperimentalunknownDetails
DB02010StaurosporineexperimentalunknownDetails
DB02052Indirubin-3'-monoximeexperimentalunknownDetails
DB04014AlsterpaulloneexperimentalunknownDetails
DB04395Phosphoaminophosphonic Acid-Adenylate EsterexperimentalunknownDetails
DB070142-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazoleexperimentalunknownDetails
DB070585-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2(3H)-thioneexperimentalunknownDetails
DB07149(7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-oneexperimentalunknownDetails
DB034446-bromoindirubin-3'-oximeexperimentalunknownDetails
DB07584N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amineexperimentalunknownDetails
DB075855-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridineexperimentalunknownDetails
DB076763-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2'H-2,3'-biindol-2'-oneexperimentalunknownDetails
DB07812N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamideexperimentalunknownDetails
DB078594-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINEexperimentalunknownDetails
DB07947ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDEexperimentalunknownDetails
DB08073(2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINEexperimentalunknownDetails
DB12129Tideglusibinvestigational, withdrawnyesantagonistDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB14507Lithium citrateapprovedunknownDetails
DB14508Lithium succinateexperimentalunknownDetails
DB14509Lithium carbonateapprovedunknownDetails