UniProt Accession

 GSK3B_HUMAN; P49841; D3DN89; Q9BWH3; Q9UL47 

Genbank Protein ID

 L33801; CH471052; CH471052; BC000251; BC012760; AF074333; AF098789 

Genbank Nucleotide ID

 AAA66475.1; EAW79533.1; EAW79536.1; AAH00251.1; AAH12760.1; AAD48517.1; AAC69340.1 

Protein Name

 Glycogen synthase kinase-3 beta 

Protein Synonyms/Alias

 GSK-3 beta; Serine/threonine-protein kinase GSK3B 

Gene Name

 GSK3B 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
15	TSFAESCKPVQQPSA	ubiquitination	[1]
86	GELVAIKKVLQDKRF	ubiquitination	[1]
183	GICHRDIKPQNLLLD	ubiquitination	[1]
197	DPDTAVLKLCDFGSA	ubiquitination	[1]
292	NPNYTEFKFPQIKAH	sumoylation	[2]
349	ELRDPNVKLPNGRDT	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Regulation of glycogen synthase kinase 3beta functions by modification of the small ubiquitin-like modifier.
 Eun Jeoung L, Sung Hee H, Jaesun C, Sung Hwa S, Kwang Hum Y, Min Kyoung K, Tae Yoon P, Sang Sun K.
 Open Biochem J. 2008;2:67-76. [PMID: 18949077] 

Functional Description

 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. 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. 

Sequence Annotation

 DOMAIN 56 340 Protein kinase.
 NP_BIND 62 70 ATP (By similarity).
 ACT_SITE 181 181 Proton acceptor.
 BINDING 85 85 ATP (By similarity).
 MOD_RES 7 7 Phosphothreonine (By similarity).
 MOD_RES 9 9 Phosphoserine; by PKB/AKT1, RPS6KA3 and
 MOD_RES 215 215 Phosphoserine (By similarity).
 MOD_RES 216 216 Phosphotyrosine.
 MOD_RES 219 219 Phosphoserine (By similarity).
 MOD_RES 389 389 Phosphoserine (By similarity).
 MOD_RES 390 390 Phosphothreonine.
 MOD_RES 395 395 Phosphothreonine (By similarity).
 MOD_RES 402 402 Phosphothreonine.  

Keyword

 3D-structure; ADP-ribosylation; Alternative splicing; Alzheimer disease; ATP-binding; Carbohydrate metabolism; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Diabetes mellitus; Differentiation; Glycogen metabolism; Kinase; Membrane; Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Signal transduction inhibitor; Transferase; Wnt signaling pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 420 AA 

Protein Sequence

Gene Ontology

 GO:0030877; C:beta-catenin destruction complex; IDA:UniProtKB.
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0043198; C:dendritic shaft; IEA:Compara.
 GO:0043197; C:dendritic spine; IEA:Compara.
 GO:0030426; C:growth cone; IEA:Compara.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0030529; C:ribonucleoprotein complex; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0002039; F:p53 binding; IDA:MGI.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0060070; P:canonical Wnt receptor signaling pathway; IC:UniProtKB.
 GO:0044337; P:canonical Wnt receptor signaling pathway involved in positive regulation of apoptotic process; IEA:Compara.
 GO:0016477; P:cell migration; IEA:Compara.
 GO:0007623; P:circadian rhythm; ISS:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0001837; P:epithelial to mesenchymal transition; IMP:UniProtKB.
 GO:0006983; P:ER overload response; IDA:MGI.
 GO:0030010; P:establishment of cell polarity; IEA:Compara.
 GO:0045444; P:fat cell differentiation; IEA:Compara.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0005977; P:glycogen metabolic process; IDA:BHF-UCL.
 GO:0021766; P:hippocampus development; IMP:BHF-UCL.
 GO:0044027; P:hypermethylation of CpG island; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0007520; P:myoblast fusion; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; TAS:UniProtKB.
 GO:0050774; P:negative regulation of dendrite morphogenesis; IEA:Compara.
 GO:2000466; P:negative regulation of glycogen (starch) synthase activity; TAS:UniProtKB.
 GO:0045719; P:negative regulation of glycogen biosynthetic process; TAS:UniProtKB.
 GO:0043407; P:negative regulation of MAP kinase activity; IEA:Compara.
 GO:0051534; P:negative regulation of NFAT protein import into nucleus; IMP:UniProtKB.
 GO:0032091; P:negative regulation of protein binding; IDA:BHF-UCL.
 GO:0031333; P:negative regulation of protein complex assembly; IMP:BHF-UCL.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Compara.
 GO:2000077; P:negative regulation of type B pancreatic cell development; TAS:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0009887; P:organ morphogenesis; IEA:Compara.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:BHF-UCL.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Compara.
 GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IEA:Compara.
 GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB.
 GO:0045732; P:positive regulation of protein catabolic process; IC:BHF-UCL.
 GO:0031334; P:positive regulation of protein complex assembly; IDA:BHF-UCL.
 GO:0046827; P:positive regulation of protein export from nucleus; IDA:MGI.
 GO:0032855; P:positive regulation of Rac GTPase activity; IMP:BHF-UCL.
 GO:2000738; P:positive regulation of stem cell differentiation; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0006611; P:protein export from nucleus; IEA:Compara.
 GO:0035372; P:protein localization to microtubule; IEA:Compara.
 GO:0000320; P:re-entry into mitotic cell cycle; IEA:Compara.
 GO:0006349; P:regulation of gene expression by genetic imprinting; IEA:Compara.
 GO:0032886; P:regulation of microtubule-based process; IMP:UniProtKB.
 GO:0048168; P:regulation of neuronal synaptic plasticity; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0010226; P:response to lithium ion; IEA:Compara.
 GO:0071109; P:superior temporal gyrus development; IMP:BHF-UCL. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS