dbPTM

GSK3A_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	GSK3A_HUMAN
UniProt AC	P49840
Protein Name	Glycogen synthase kinase-3 alpha
Gene Name	GSK3A
Organism	Homo sapiens (Human).
Sequence Length	483
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	MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGVCHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLPPLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLTNSS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSGGGPSGG ------CCCCCCCCC	46.26	18691976
2	Phosphorylation	------MSGGGPSGG ------CCCCCCCCC	46.26	25159151
7	Phosphorylation	-MSGGGPSGGGPGGS -CCCCCCCCCCCCCC	54.03	23663014
14	Phosphorylation	SGGGPGGSGRARTSS CCCCCCCCCCCCCCC	30.90	25849741
16	Methylation	GGPGGSGRARTSSFA CCCCCCCCCCCCCCC	23.69	-
19	Phosphorylation	GGSGRARTSSFAEPG CCCCCCCCCCCCCCC	27.95	22322096
20	Phosphorylation	GSGRARTSSFAEPGG CCCCCCCCCCCCCCC	20.22	27273156
21	Phosphorylation	SGRARTSSFAEPGGG CCCCCCCCCCCCCCC	28.06	11085518
39	Phosphorylation	GGGGPGGSASGPGGT CCCCCCCCCCCCCCC	25.77	22322096
41	Phosphorylation	GGPGGSASGPGGTGG CCCCCCCCCCCCCCC	47.41	22322096
46	Phosphorylation	SASGPGGTGGGKASV CCCCCCCCCCCCCCC	38.27	22322096
52	Phosphorylation	GTGGGKASVGAMGGG CCCCCCCCCCCCCCC	25.27	28857561
63	Phosphorylation	MGGGVGASSSGGGPG CCCCCCCCCCCCCCC	21.07	18691976
64	Phosphorylation	GGGVGASSSGGGPGG CCCCCCCCCCCCCCC	32.25	18691976
65	Phosphorylation	GGVGASSSGGGPGGS CCCCCCCCCCCCCCC	38.67	28857561
72	Phosphorylation	SGGGPGGSGGGGSGG CCCCCCCCCCCCCCC	39.93	25159151
77	Phosphorylation	GGSGGGGSGGPGAGT CCCCCCCCCCCCCCC	43.80	30175587
84	Phosphorylation	SGGPGAGTSFPPPGV CCCCCCCCCCCCCCC	27.02	18691976
85	Phosphorylation	GGPGAGTSFPPPGVK CCCCCCCCCCCCCCC	34.53	28857561
97	Phosphorylation	GVKLGRDSGKVTTVV CCCCCCCCCCEEEEE	38.87	22817900
101	Phosphorylation	GRDSGKVTTVVATLG CCCCCCEEEEEEECC	19.84	18691976
106	O-linked_Glycosylation	KVTTVVATLGQGPER CEEEEEEECCCCCCH	21.58	28657654
114	Phosphorylation	LGQGPERSQEVAYTD CCCCCCHHCEEEEEE	29.09	23532336
123	Acetylation	EVAYTDIKVIGNGSF EEEEEEEEEECCCCC	30.52	7684835
129	Phosphorylation	IKVIGNGSFGVVYQA EEEECCCCCEEEEEE	23.87	25693802
134	Phosphorylation	NGSFGVVYQARLAET CCCCEEEEEEEHHHH	8.27	23917254
141	Phosphorylation	YQARLAETRELVAIK EEEEHHHHHHHHHHH	24.68	24719451
148	2-Hydroxyisobutyrylation	TRELVAIKKVLQDKR HHHHHHHHHHHHCCC	27.39	-
166	Ubiquitination	RELQIMRKLDHCNIV HHHHHHHHCCCCCEE	40.67	-
177	Phosphorylation	CNIVRLRYFFYSSGE CCEEEEEEEEECCCC	11.57	-
180	Phosphorylation	VRLRYFFYSSGEKKD EEEEEEEECCCCCCC	7.63	-
197	Phosphorylation	YLNLVLEYVPETVYR EHHHHHHHCHHHHHH	19.69	-
220	Phosphorylation	KLTIPILYVKVYMYQ CCCHHHHHHHHHHHH	10.03	22817900
246	Ubiquitination	GVCHRDIKPQNLLVD CEECCCCCCHHEEEC	44.85	-
260	Ubiquitination	DPDTAVLKLCDFGSA CCCCHHHHHCCCCCH	40.23	-
266	Phosphorylation	LKLCDFGSAKQLVRG HHHCCCCCHHHHHCC	32.08	-
268	Ubiquitination	LCDFGSAKQLVRGEP HCCCCCHHHHHCCCC	45.95	-
278	Phosphorylation	VRGEPNVSYICSRYY HCCCCCHHHHHCCCC	18.54	29255136
279	Phosphorylation	RGEPNVSYICSRYYR CCCCCHHHHHCCCCC	11.15	19664994
282	Phosphorylation	PNVSYICSRYYRAPE CCHHHHHCCCCCCCC	17.48	23927012
284	Phosphorylation	VSYICSRYYRAPELI HHHHHCCCCCCCCHH	4.88	28152594
285	Phosphorylation	SYICSRYYRAPELIF HHHHCCCCCCCCHHC	10.13	28152594
338	Phosphorylation	EIIKVLGTPTREQIR HHHHHHCCCCHHHHH	19.82	17192257
340	Phosphorylation	IKVLGTPTREQIREM HHHHCCCCHHHHHHH	46.83	17192257
351	Phosphorylation	IREMNPNYTEFKFPQ HHHHCCCCCCCCCCC	14.65	-
355	Ubiquitination	NPNYTEFKFPQIKAH CCCCCCCCCCCCCCC	50.32	21890473
360	Ubiquitination	EFKFPQIKAHPWTKV CCCCCCCCCCCCHHH	35.08	21890473
366	Ubiquitination	IKAHPWTKVFKSRTP CCCCCCHHHCCCCCC	41.63	-
401	Phosphorylation	PLEACAHSFFDELRC HHHHHHHHHHHHHHH	14.75	19369195
453	Phosphorylation	RSPAGTTTLTPSSQA CCCCCCCEECCCCCC	28.59	-
466	Phosphorylation	QALTETPTSSDWQST CCCCCCCCCCCCCCC	48.56	-
478	Phosphorylation	QSTDATPTLTNSS-- CCCCCCCCCCCCC--	41.69	18691976
480	Phosphorylation	TDATPTLTNSS---- CCCCCCCCCCC----	35.22	17192257
482	Phosphorylation	ATPTLTNSS------ CCCCCCCCC------	31.99	30576142
483	Phosphorylation	TPTLTNSS------- CCCCCCCC-------	46.43	27251275

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	PRKCH	P24723	GPS
21	S	Phosphorylation	Kinase	PKC_GROUP	-	PhosphoELM
21	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
21	S	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM
21	S	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
21	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
21	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
21	S	Phosphorylation	Kinase	SGK3	Q96BR1	GPS
21	S	Phosphorylation	Kinase	RPS6KA3	P51812	GPS
21	S	Phosphorylation	Kinase	AKT1	P31749	Uniprot
21	S	Phosphorylation	Kinase	PRKCG	P05129	GPS
21	S	Phosphorylation	Kinase	PRKCD	Q05655	GPS
21	S	Phosphorylation	Kinase	PKCB ISO2	P05771-2	PSP
21	S	Phosphorylation	Kinase	PRKCB	P05771	GPS
21	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
21	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
21	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
279	Y	Phosphorylation	Kinase	GSK3A	P49840	PSP

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.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of GSK3A_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ANDR_HUMAN	AR	physical	15361837
MYC_HUMAN	MYC	physical	14563837
EBP2_HUMAN	EBNA1BP2	physical	21220517
GLI3_HUMAN	GLI3	physical	16371461
CREB1_HUMAN	CREB1	physical	14635195
TAU_HUMAN	MAPT	physical	9735171
TAU_HUMAN	MAPT	physical	7931292
KAPCA_HUMAN	PRKACA	physical	11035810
AKT1_HUMAN	AKT1	physical	21775285
HS90A_HUMAN	HSP90AA1	physical	22939624
DEAF1_HUMAN	DEAF1	physical	20368287
SPICE_HUMAN	SPICE1	physical	20368287
M3K11_HUMAN	MAP3K11	physical	20368287
NBR1_HUMAN	NBR1	physical	20368287
VTA1_HUMAN	VTA1	physical	20368287
SPICE_MOUSE	Spice1	physical	20368287
DEAF1_MOUSE	Deaf1	physical	20368287
LZTS2_MOUSE	Lzts2	physical	20368287
M3K11_MOUSE	Map3k11	physical	20368287
NBR1_MOUSE	Nbr1	physical	20368287
NONO_MOUSE	Nono	physical	20368287
PRUN1_MOUSE	Prune	physical	20368287
VTA1_MOUSE	Vta1	physical	20368287
PROX2_MOUSE	Prox2	physical	20368287
KRBA1_MOUSE	Krba1	physical	20368287
ZBED3_MOUSE	Zbed3	physical	20368287
GSKIP_HUMAN	GSKIP	physical	20368287
SPG21_HUMAN	SPG21	physical	20368287
ARHGB_HUMAN	ARHGEF11	physical	20368287
KRBA1_HUMAN	KRBA1	physical	20368287
AXIN1_MOUSE	Axin1	physical	20368287
F193B_HUMAN	FAM193B	physical	20368287
PSMD1_HUMAN	PSMD1	physical	23602568
AXIN1_HUMAN	AXIN1	physical	23602568
AXIN2_HUMAN	AXIN2	physical	23602568
GSKIP_HUMAN	GSKIP	physical	23602568
IPP2_HUMAN	PPP1R2	physical	23602568
FRAT1_HUMAN	FRAT1	physical	23602568
AKAP9_HUMAN	AKAP9	physical	23602568
NBR1_HUMAN	NBR1	physical	24879152
RICTR_HUMAN	RICTOR	physical	25897075
CTNB1_HUMAN	CTNNB1	physical	25897075
CRBG1_HUMAN	AIM1	physical	26496610
CTNA1_HUMAN	CTNNA1	physical	26496610
CTNB1_HUMAN	CTNNB1	physical	26496610
AXIN1_HUMAN	AXIN1	physical	26496610
MDN1_HUMAN	MDN1	physical	26496610
RPC2_HUMAN	POLR3B	physical	26496610
B2CL1_HUMAN	BCL2L1	physical	22617334

Drug and Disease Associations

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

Regulatory Network of GSK3A_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-19; SER-20;SER-21; SER-39; SER-41; SER-63; SER-65; SER-72; SER-77; THR-84; SER-97AND THR-480, AND MASS SPECTROMETRY.	19369195 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; TYR-279 AND SER-282,AND MASS SPECTROMETRY.	19413330 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-72, AND MASSSPECTROMETRY.	18691976 [Abstract]
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry."; Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.; Mol. Cell. Proteomics 6:537-547(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21 AND TYR-279, AND MASSSPECTROMETRY.	17192257 [Abstract]
"Phosphoproteome of resting human platelets."; Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.; J. Proteome Res. 7:526-534(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-279, AND MASSSPECTROMETRY.	18088087 [Abstract]
"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks."; Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.; Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-279, AND MASSSPECTROMETRY.	17389395 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-279, AND MASSSPECTROMETRY.	18083107 [Abstract]
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells."; Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.; Nat. Biotechnol. 23:94-101(2005). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-279, AND MASSSPECTROMETRY.	15592455 [Abstract]

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