GSK3A_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: GSK3A_RAT
• UniProt AC: P18265
• Protein Name: Glycogen synthase kinase-3 alpha
• Gene Name: Gsk3a
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 483
• Protein 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. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation..
• Protein Sequence: MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPSGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLIIPIIYVKVYMYQLFRSLAYIHSQGVCHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRSLGTQLPNNRPLPPLFNFSPGELSIQPSLNAILIPPHLRSPSGPATLTSSSQALTETQTGQDWQAPDATPTLTNSS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSGGGPSGG ------CCCCCCCCC	46.26	-
2	Phosphorylation	------MSGGGPSGG ------CCCCCCCCC	46.26	27097102
19	Phosphorylation	GGSGRARTSSFAEPG CCCCCCCCCCCCCCC	27.95	28689409
20	Phosphorylation	GSGRARTSSFAEPGG CCCCCCCCCCCCCCC	20.22	23589303
21	Phosphorylation	SGRARTSSFAEPGGG CCCCCCCCCCCCCCC	28.06	11978789
39	Phosphorylation	GGGGPGGSASGPGGT CCCCCCCCCCCCCCC	25.77	27097102
41	Phosphorylation	GGPGGSASGPGGTGG CCCCCCCCCCCCCCC	47.41	27097102
46	Phosphorylation	SASGPGGTGGGKASV CCCCCCCCCCCCCCC	38.27	27097102
52	Phosphorylation	GTGGGKASVGAMGGG CCCCCCCCCCCCCCC	25.27	27097102
63	Phosphorylation	MGGGVGASSSGGGPS CCCCCCCCCCCCCCC	21.07	27097102
64	Phosphorylation	GGGVGASSSGGGPSG CCCCCCCCCCCCCCC	32.25	27097102
65	Phosphorylation	GGVGASSSGGGPSGS CCCCCCCCCCCCCCC	38.67	27097102
70	Phosphorylation	SSSGGGPSGSGGGGS CCCCCCCCCCCCCCC	49.19	27097102
72	Phosphorylation	SGGGPSGSGGGGSGG CCCCCCCCCCCCCCC	38.31	27097102
77	Phosphorylation	SGSGGGGSGGPGAGT CCCCCCCCCCCCCCC	43.80	27097102
84	Phosphorylation	SGGPGAGTSFPPPGV CCCCCCCCCCCCCCC	27.02	27097102
85	Phosphorylation	GGPGAGTSFPPPGVK CCCCCCCCCCCCCCC	34.53	27097102
97	Phosphorylation	GVKLGRDSGKVTTVV CCCCCCCCCCEEEEE	38.87	-
134	Phosphorylation	NGSFGVVYQARLAET CCCCEEEEEEEHHHH	8.27	-
278	Phosphorylation	VRGEPNVSYICSRYY HCCCCCHHHHHCCCC	18.54	28825834
279	Phosphorylation	RGEPNVSYICSRYYR CCCCCHHHHHCCCCC	11.15	18331841
282	Phosphorylation	PNVSYICSRYYRAPE CCHHHHHCCCCCCCC	17.48	27097102
284	Phosphorylation	VSYICSRYYRAPELI HHHHHCCCCCCCCHH	4.88	-
366	Acetylation	IKAHPWTKVFKSRTP CCCCCCHHHCCCCCC	41.63	22902405
453	Phosphorylation	RSPSGPATLTSSSQA CCCCCCCEECCCCCC	33.43	-
466	Phosphorylation	QALTETQTGQDWQAP CCCCCCCCCCCCCCC	44.20	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
21	S	Phosphorylation	Kinase	AKT1	P31749	PSP
21	S	Phosphorylation	Kinase	AKT1	P47196	Uniprot
21	S	Phosphorylation	Kinase	MAPKAPK2	F1M9C0	GPS
21	S	Phosphorylation	Kinase	PKACA	P17612	PSP
21	S	Phosphorylation	Kinase	PRKACA	P27791	GPS
21	S	Phosphorylation	Kinase	CAMK2B	Q13554	PSP
21	S	Phosphorylation	Kinase	CAMK2B	P08413	PSP
21	S	Phosphorylation	Kinase	PRKCB	P68404	GPS
21	S	Phosphorylation	Kinase	RPS6KB1	P67999	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
21	S	Phosphorylation	Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3A, resulting in the dephosphorylation and activation of GYS1.	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of GSK3A_RAT !!

Protein-Protein Interaction

Oops, there are no PPI records of GSK3A_RAT !!

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Modulation of the glycogen synthase kinase-3 family by tyrosinephosphorylation.";
Hughes K., Nikolakaki E., Plyte S.E., Totty N.F., Woodgett J.R.;
EMBO J. 12:803-808(1993).
Cited for: PHOSPHORYLATION AT TYR-279.
PubMed: 8382613