CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008221
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Glycogen synthase kinase-3 alpha 
Protein Synonyms/Alias
 GSK-3 alpha; Serine/threonine-protein kinase GSK3A 
Gene Name
 GSK3A 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
166RELQIMRKLDHCNIVubiquitination[1]
246GVCHRDIKPQNLLVDubiquitination[1]
260DPDTAVLKLCDFGSAubiquitination[1]
268LCDFGSAKQLVRGEPubiquitination[1, 2]
355NPNYTEFKFPQIKAHubiquitination[1, 3, 4, 5]
360EFKFPQIKAHPWTKVubiquitination[2, 3, 4, 5]
366IKAHPWTKVFKSRTPubiquitination[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] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
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), 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. Regulates glycogen metabolism in liver, but not in muscle. 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. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. 
Sequence Annotation
 DOMAIN 119 403 Protein kinase.
 NP_BIND 125 133 ATP (By similarity).
 ACT_SITE 244 244 Proton acceptor (By similarity).
 BINDING 148 148 ATP (By similarity).
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 2 2 Phosphoserine.
 MOD_RES 21 21 Phosphoserine; by PKB/AKT1.
 MOD_RES 72 72 Phosphoserine.
 MOD_RES 77 77 Phosphoserine.
 MOD_RES 97 97 Phosphoserine.
 MOD_RES 279 279 Phosphotyrosine (By similarity).  
Keyword
 3D-structure; Acetylation; Alzheimer disease; ATP-binding; Carbohydrate metabolism; Complete proteome; Diabetes mellitus; Glycogen metabolism; Kinase; Neurogenesis; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Signal transduction inhibitor; Transferase; Wnt signaling pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 483 AA 
Protein Sequence
MSGGGPSGGG PGGSGRARTS SFAEPGGGGG GGGGGPGGSA SGPGGTGGGK ASVGAMGGGV 60
GASSSGGGPG GSGGGGSGGP GAGTSFPPPG VKLGRDSGKV TTVVATLGQG PERSQEVAYT 120
DIKVIGNGSF GVVYQARLAE TRELVAIKKV LQDKRFKNRE LQIMRKLDHC NIVRLRYFFY 180
SSGEKKDELY LNLVLEYVPE TVYRVARHFT KAKLTIPILY VKVYMYQLFR SLAYIHSQGV 240
CHRDIKPQNL LVDPDTAVLK LCDFGSAKQL VRGEPNVSYI CSRYYRAPEL IFGATDYTSS 300
IDVWSAGCVL AELLLGQPIF PGDSGVDQLV EIIKVLGTPT REQIREMNPN YTEFKFPQIK 360
AHPWTKVFKS RTPPEAIALC SSLLEYTPSS RLSPLEACAH SFFDELRCLG TQLPNNRPLP 420
PLFNFSAGEL SIQPSLNAIL IPPHLRSPAG TTTLTPSSQA LTETPTSSDW QSTDATPTLT 480
NSS 483 
Gene Ontology
 GO:0030877; C:beta-catenin destruction complex; TAS:UniProtKB.
 GO:0005829; C:cytosol; TAS:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0050321; F:tau-protein kinase activity; TAS:UniProtKB.
 GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
 GO:0003214; P:cardiac left ventricle morphogenesis; ISS:BHF-UCL.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0005977; P:glycogen metabolic process; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; ISS:BHF-UCL.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; TAS:UniProtKB.
 GO:0061052; P:negative regulation of cell growth involved in cardiac muscle cell development; ISS:BHF-UCL.
 GO:0046325; P:negative regulation of glucose import; IMP:BHF-UCL.
 GO:2000466; P:negative regulation of glycogen (starch) synthase activity; TAS:UniProtKB.
 GO:0045719; P:negative regulation of glycogen biosynthetic process; TAS:UniProtKB.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
 GO:0032007; P:negative regulation of TOR signaling cascade; ISS:BHF-UCL.
 GO:2000077; P:negative regulation of type B pancreatic cell development; TAS:UniProtKB.
 GO:0010905; P:negative regulation of UDP-glucose catabolic process; IC:UniProtKB.
 GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0071879; P:positive regulation of adrenergic receptor signaling pathway; ISS:BHF-UCL.
 GO:0030819; P:positive regulation of cAMP biosynthetic process; ISS:BHF-UCL.
 GO:2000467; P:positive regulation of glycogen (starch) synthase activity; ISS:BHF-UCL.
 GO:0045823; P:positive regulation of heart contraction; ISS:BHF-UCL.
 GO:0045732; P:positive regulation of protein catabolic process; NAS:BHF-UCL.
 GO:0003073; P:regulation of systemic arterial blood pressure; ISS:BHF-UCL.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 
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