GSK3A
entrez
2931
canonical
uniprot
P49840
canonical
ensembl
ENSG00000105723
resolver
ensp
ENSP00000222330
resolver
ensp
ENSP00000412663
resolver
enst
ENST00000222330
resolver
enst
ENST00000453535
resolver
genesymbol
GSK3A
resolver
hgnc
HGNC:4616
resolver
uniprot
O14959
resolver
uniprot_entry
GSK3A_HUMAN
resolver
uniprot_sec
O14959
resolver
activity_regulation
ACTIVITY REGULATION: Activated by phosphorylation at Tyr-279. In response to insulin, inhibited by phosphorylation at Ser-21 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium. {ECO:0000269|PubMed:11749387, ECO:0000269|PubMed:19366350}.
uniprot
proteins
amino_acid_sequence
MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGVCHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLPPLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLTNSS
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
ec_number
2.7.11.26
uniprot
proteins
function
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 (PubMed:11749387, PubMed:17478001, PubMed:19366350). Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350). 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 (PubMed:10868943, PubMed:17478001). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity). 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 which activates KAT5/TIP60 acetyltransferase activity and promotes acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). 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). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). {ECO:0000250|UniProtKB:P18265, ECO:0000250|UniProtKB:P49841, ECO:0000250|UniProtKB:Q2NL51, ECO:0000269|PubMed:10868943, ECO:0000269|PubMed:12761548, ECO:0000269|PubMed:17229088, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:30704899, ECO:0000303|PubMed:11749387, ECO:0000303|PubMed:17478001, ECO:0000303|PubMed:19366350}.
uniprot
proteins
mass_dalton
50981
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and deactivates GSK3A, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-279.; PTM: (Microbial infection) Dephosphorylated at Tyr-279 by M.tuberculosis PtpA, which leads to prevention of apoptosis during early stages of microbial infection. {ECO:0000269|PubMed:25187516}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
GSK-3 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10868943
uniprot
proteins
pubmed
11749387
uniprot
proteins
pubmed
12761548
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17229088
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17478001
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18846110
uniprot
proteins
pubmed
19366350
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19706605
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22539723
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25187516
uniprot
proteins
pubmed
25897075
uniprot
proteins
pubmed
30704899
uniprot
proteins
pubmed
31073040
uniprot
proteins
sequence_length
483
uniprot
proteins