Glycogen synthase kinase-3 beta

NameGlycogen synthase kinase-3 beta
Synonyms2.7.11.26 GSK-3 beta Serine/threonine-protein kinase GSK3B
Gene NameGSK3B
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002121|Glycogen synthase kinase-3 beta
MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTK
VIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSG
EKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHR
DIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDV
WSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHP
WTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALF
NFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST
Number of residues420
Molecular Weight46743.865
Theoretical pI8.97
GO Classification
Functions
    protein kinase binding
beta-catenin binding
ubiquitin protein ligase binding
protein kinase A catalytic subunit binding
RNA polymerase II transcription factor binding
tau-protein kinase activity
p53 binding
ATP binding
kinase activity
NF-kappaB binding
protein serine/threonine kinase activity
Processes
    positive regulation of protein catabolic process
fibroblast growth factor receptor signaling pathway
positive regulation of peptidyl-threonine phosphorylation
negative regulation of cardiac muscle hypertrophy
positive regulation of axon extension
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
negative regulation of apoptotic process
regulation of cellular response to heat
protein localization to microtubule
positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
negative regulation of canonical Wnt signaling pathway
negative regulation of protein complex assembly
positive regulation of protein complex assembly
negative regulation of neuron projection development
glycogen metabolic process
regulation of microtubule-based process
neurotrophin TRK receptor signaling pathway
canonical Wnt signaling pathway
negative regulation of neuron maturation
hippocampus development
positive regulation of protein export from nucleus
positive regulation of peptidyl-serine phosphorylation
negative regulation of protein binding
re-entry into mitotic cell cycle
phosphatidylinositol-mediated signaling
axon guidance
positive regulation of transcription from RNA polymerase II promoter
ER overload response
protein autophosphorylation
fat cell differentiation
positive regulation of protein binding
hypermethylation of CpG island
cell migration
protein phosphorylation
extrinsic apoptotic signaling pathway in absence of ligand
positive regulation of stem cell differentiation
protein export from nucleus
epithelial to mesenchymal transition
negative regulation of glycogen (starch) synthase activity
epidermal growth factor receptor signaling pathway
intracellular signal transduction
canonical Wnt signaling pathway involved in positive regulation of apoptotic process
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
cellular response to interleukin-3
myoblast fusion
negative regulation of glycogen biosynthetic process
innate immune response
circadian rhythm
negative regulation of protein localization to nucleus
organ morphogenesis
positive regulation of cell-matrix adhesion
negative regulation of type B pancreatic cell development
Fc-epsilon receptor signaling pathway
positive regulation of GTPase activity
superior temporal gyrus development
negative regulation of NFAT protein import into nucleus
peptidyl-serine phosphorylation
positive regulation of canonical Wnt signaling pathway
cellular response to heat
regulation of gene expression by genetic imprinting
Components
    nucleus
plasma membrane
growth cone
cytosol
beta-catenin destruction complex
neuronal postsynaptic density
perinuclear region of cytoplasm
centrosome
dendritic shaft
cytoplasm
neuronal cell body
ribonucleoprotein complex
General FunctionUbiquitin protein ligase binding
Specific FunctionConstitutively 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).
Transmembrane Regions
GenBank Protein ID529237
UniProtKB IDP49841
UniProtKB Entry NameGSK3B_HUMAN
Cellular LocationCytoplasm
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
GenBank Gene IDL33801
GeneCard IDNone
GenAtlas IDGSK3B
HGNC IDHGNC:4617
Chromosome Location3
Locus3q13.3
References
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