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Overview

Uniprot IDP18265
Protein NameGlycogen synthase kinase-3 alpha
Gene NameGsk3a
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
99 KLGRDSGKVTTVVAT

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), CTNNB1/beta-catenin, APC and AXIN1. Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (By similarity). Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (By similarity). May be involved in the regulation of replication in pancreatic beta-cells (PubMed:17242403). Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (By similarity). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity)

Protein Sequence

10 MSGGGPSGGG 20 PGGSGRARTS 30 SFAEPGGGGG 40 GGGGGPGGSA 50 SGPGGTGGGK 60 ASVGAMGGGV 70 GASSSGGGPS 80 GSGGGGSGGP 90 GAGTSFPPPG 100 VKLGRDSGKV 110 TTVVATLGQG 120 PERSQEVAYT 130 DIKVIGNGSF 140 GVVYQARLAE 150 TRELVAIKKV 160 LQDKRFKNRE 170 LQIMRKLDHC 180 NIVRLRYFFY 190 SSGEKKDELY 200 LNLVLEYVPE 210 TVYRVARHFT 220 KAKLIIPIIY 230 VKVYMYQLFR 240 SLAYIHSQGV 250 CHRDIKPQNL 260 LVDPDTAVLK 270 LCDFGSAKQL 280 VRGEPNVSYI 290 CSRYYRAPEL 300 IFGATDYTSS 310 IDVWSAGCVL 320 AELLLGQPIF 330 PGDSGVDQLV 340 EIIKVLGTPT 350 REQIREMNPN 360 YTEFKFPQIK 370 AHPWTKVFKS 380 RTPPEAIALC 390 SSLLEYTPSS 400 RLSPLEACAH 410 SFFDELRSLG 420 TQLPNNRPLP 430 PLFNFSPGEL 440 SIQPSLNAIL 450 IPPHLRSPSG 460 PATLTSSSQA 470 LTETQTGQDW 480 QAPDATPTLT NSS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0030424 axon
Cellular Component GO:0005874 microtubule
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0034236 protein kinase A catalytic subunit binding
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0120283 protein serine/threonine kinase binding
Molecular Function GO:0005102 signaling receptor binding
Molecular Function GO:0050321 tau-protein kinase activity
Biological Process GO:0141068 autosome genomic imprinting
Biological Process GO:0003214 cardiac left ventricle morphogenesis
Biological Process GO:0030154 cell differentiation
Biological Process GO:0016477 cell migration
Biological Process GO:0071385 cellular response to glucocorticoid stimulus
Biological Process GO:0032869 cellular response to insulin stimulus
Biological Process GO:0036016 cellular response to interleukin-3
Biological Process GO:0071285 cellular response to lithium ion
Biological Process GO:0097191 extrinsic apoptotic signaling pathway
Biological Process GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
Biological Process GO:0005977 glycogen metabolic process
Biological Process GO:0008286 insulin receptor signaling pathway
Biological Process GO:0031663 lipopolysaccharide-mediated signaling pathway
Biological Process GO:0090090 negative regulation of canonical Wnt signaling pathway
Biological Process GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development
Biological Process GO:0046325 negative regulation of D-glucose import across plasma membrane
Biological Process GO:2000171 negative regulation of dendrite development
Biological Process GO:0046627 negative regulation of insulin receptor signaling pathway
Biological Process GO:0032007 negative regulation of TOR signaling
Biological Process GO:0007399 nervous system development
Biological Process GO:0071879 positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway
Biological Process GO:0106071 positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
Biological Process GO:1902004 positive regulation of amyloid-beta formation
Biological Process GO:0010508 positive regulation of autophagy
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:0045823 positive regulation of heart contraction
Biological Process GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
Biological Process GO:0043525 positive regulation of neuron apoptotic process
Biological Process GO:0033138 positive regulation of peptidyl-serine phosphorylation
Biological Process GO:0010800 positive regulation of peptidyl-threonine phosphorylation
Biological Process GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process GO:1903955 positive regulation of protein targeting to mitochondrion
Biological Process GO:0031398 positive regulation of protein ubiquitination
Biological Process GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0070507 regulation of microtubule cytoskeleton organization
Biological Process GO:1901524 regulation of mitophagy
Biological Process GO:0010975 regulation of neuron projection development
Biological Process GO:0003073 regulation of systemic arterial blood pressure
Biological Process GO:0016055 Wnt signaling pathway
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol

Reference

[1] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.