dbPTM

GSK3A_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	GSK3A_MOUSE
UniProt AC	Q2NL51
Protein Name	Glycogen synthase kinase-3 alpha
Gene Name	Gsk3a
Organism	Mus musculus (Mouse).
Sequence Length	490
Subcellular Localization
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	MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPSGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATVGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLITPIIYIKVYMYQLFRSLAYIHSQGVCHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFKSSKTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRRLGAQLPNDRPLPPLFNFSPGELSIQPSLNAILIPPHLRSPAGPASPLTTSYNPSSQALTEAQTGQDWQPSDATTATLASSS

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	30352176
7	Phosphorylation	-MSGGGPSGGGPGGS -CCCCCCCCCCCCCC	54.03	26643407
14	Phosphorylation	SGGGPGGSGRARTSS CCCCCCCCCCCCCCC	30.90	26643407
19	Phosphorylation	GGSGRARTSSFAEPG CCCCCCCCCCCCCCC	27.95	25521595
20	Phosphorylation	GSGRARTSSFAEPGG CCCCCCCCCCCCCCC	20.22	23684622
21	Phosphorylation	SGRARTSSFAEPGGG CCCCCCCCCCCCCCC	28.06	25521595
39	Phosphorylation	GGGGPGGSASGPGGT CCCCCCCCCCCCCCC	25.77	25521595
41	Phosphorylation	GGPGGSASGPGGTGG CCCCCCCCCCCCCCC	47.41	25521595
46	Phosphorylation	SASGPGGTGGGKASV CCCCCCCCCCCCCCC	38.27	25777480
52	Phosphorylation	GTGGGKASVGAMGGG CCCCCCCCCCCCCCC	25.27	25293948
63	Phosphorylation	MGGGVGASSSGGGPS CCCCCCCCCCCCCCC	21.07	25293948
64	Phosphorylation	GGGVGASSSGGGPSG CCCCCCCCCCCCCCC	32.25	25293948
65	Phosphorylation	GGVGASSSGGGPSGS CCCCCCCCCCCCCCC	38.67	25293948
70	Phosphorylation	SSSGGGPSGSGGGGS CCCCCCCCCCCCCCC	49.19	19060867
72	Phosphorylation	SGGGPSGSGGGGSGG CCCCCCCCCCCCCCC	38.31	19060867
77	Phosphorylation	SGSGGGGSGGPGAGT CCCCCCCCCCCCCCC	43.80	22817900
84	Phosphorylation	SGGPGAGTSFPPPGV CCCCCCCCCCCCCCC	27.02	22817900
85	Phosphorylation	GGPGAGTSFPPPGVK CCCCCCCCCCCCCCC	34.53	22817900
97	Phosphorylation	GVKLGRDSGKVTTVV CCCCCCCCCCEEEEE	38.87	-
114	Phosphorylation	VGQGPERSQEVAYTD ECCCCHHCCEEEEEE	29.09	24719451
119	Phosphorylation	ERSQEVAYTDIKVIG HHCCEEEEEEEEEEC	15.32	24719451
134	Phosphorylation	NGSFGVVYQARLAET CCCCEEEEEEEHHHH	8.27	25367039
166	Acetylation	RELQIMRKLDHCNIV HHHHHHHHCCCCCEE	40.67	22826441
216	Phosphorylation	FTKAKLITPIIYIKV HHHHHCCHHHHHHHH	20.90	24719451
220	Phosphorylation	KLITPIIYIKVYMYQ HCCHHHHHHHHHHHH	8.73	24719451
268	Ubiquitination	LCDFGSAKQLVRGEP HCCCCCHHHHHCCCC	45.95	-
278	Phosphorylation	VRGEPNVSYICSRYY HCCCCCHHHHHCCCC	18.54	24925903
279	Phosphorylation	RGEPNVSYICSRYYR CCCCCHHHHHCCCCC	11.15	18388127
282	Phosphorylation	PNVSYICSRYYRAPE CCHHHHHCCCCCCCC	17.48	25521595
291	Ubiquitination	YYRAPELIFGATDYT CCCCCCHHCCCCCCC	2.60	27667366
338	Phosphorylation	EIIKVLGTPTREQIR HHHHHHCCCCHHHHH	19.82	25338131
355	Ubiquitination	NPNYTEFKFPQIKAH CCCCCCCCCCCCCCC	50.32	27667366
372	Ubiquitination	TKVFKSSKTPPEAIA HHHCCCCCCCHHHHH	72.62	22790023
394	Phosphorylation	YTPSSRLSPLEACAH HCCCCCCCHHHHHHH	26.74	26239621
402	Phosphorylation	PLEACAHSFFDELRR HHHHHHHHHHHHHHH	14.75	26239621
454	Phosphorylation	RSPAGPASPLTTSYN CCCCCCCCCCCCCCC	24.47	25521595
472	Phosphorylation	QALTEAQTGQDWQPS HHHHHCCCCCCCCCC	43.81	-
479	Phosphorylation	TGQDWQPSDATTATL CCCCCCCCCCHHHHH	25.44	26643407
482	Phosphorylation	DWQPSDATTATLASS CCCCCCCHHHHHCCC	23.19	26643407
483	Phosphorylation	WQPSDATTATLASSS CCCCCCHHHHHCCCC	21.26	26643407
485	Phosphorylation	PSDATTATLASSS-- CCCCHHHHHCCCC--	22.29	26643407
488	Phosphorylation	ATTATLASSS----- CHHHHHCCCC-----	33.94	26643407
489	Phosphorylation	TTATLASSS------ HHHHHCCCC------	34.16	26643407
490	Phosphorylation	TATLASSS------- HHHHCCCC-------	41.57	26643407

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	P31750	Uniprot
21	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
21	S	Phosphorylation	Kinase	PRKCB	P05771	GPS
21	S	Phosphorylation	Kinase	PRKCH	P24723	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
21	S	Phosphorylation		15791206
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.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of GSK3A_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
CTND1_MOUSE	Ctnnd1	physical	19706605

Drug and Disease Associations

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

Regulatory Network of GSK3A_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Role that phosphorylation of GSK3 plays in insulin and Wnt signallingdefined by knockin analysis."; McManus E.J., Sakamoto K., Armit L.J., Ronaldson L., Shpiro N.,Marquez R., Alessi D.R.; EMBO J. 24:1571-1583(2005). Cited for: FUNCTION, MUTAGENESIS OF SER-21, AND PHOSPHORYLATION AT SER-21.	15791206 [Abstract]

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