dbPTM

GSK3B_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	GSK3B_MOUSE
UniProt AC	Q9WV60
Protein Name	Glycogen synthase kinase-3 beta
Gene Name	Gsk3b
Organism	Mus musculus (Mouse).
Sequence Length	420
Subcellular Localization	Cytoplasm. Nucleus. Cell membrane. The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane (By similarity)..
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), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-679' upon T-cell activation. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity..
Protein Sequence	MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALFNFTTQELSSNPPLATILIPPHARIQAAASPPANATAASDTNAGDRGQTNNAASASASNST

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSGRPRTTS ------CCCCCCCCC	43.43	23375375
7	Phosphorylation	-MSGRPRTTSFAESC -CCCCCCCCCHHHHC	29.49	22322096
8	Phosphorylation	MSGRPRTTSFAESCK CCCCCCCCCHHHHCC	24.11	22322096
9	O-linked_Glycosylation	SGRPRTTSFAESCKP CCCCCCCCHHHHCCC	23.11	22645316
9	Phosphorylation	SGRPRTTSFAESCKP CCCCCCCCHHHHCCC	23.11	22322096
13	Phosphorylation	RTTSFAESCKPVQQP CCCCHHHHCCCCCCC	24.82	25521595
21	Phosphorylation	CKPVQQPSAFGSMKV CCCCCCCCCCCCEEE	31.71	15710331
25	Phosphorylation	QQPSAFGSMKVSRDK CCCCCCCCEEEEECC	14.69	22322096
35	Phosphorylation	VSRDKDGSKVTTVVA EEECCCCCEEEEEEE	33.80	29899451
55	Phosphorylation	PDRPQEVSYTDTKVI CCCCCEEEEEEEEEE	22.89	29899451
205	Ubiquitination	LCDFGSAKQLVRGEP HCCCCCHHHHHCCCC	45.95	-
215	Phosphorylation	VRGEPNVSYICSRYY HCCCCCHHHHHCCCC	18.54	24925903
216	Phosphorylation	RGEPNVSYICSRYYR CCCCCHHHHHCCCCC	11.15	18388127
219	Phosphorylation	PNVSYICSRYYRAPE CCHHHHHCCCCCCCC	17.48	25521595
275	Phosphorylation	EIIKVLGTPTREQIR HHHHHHCCCCHHHHH	19.82	25338131
292	Ubiquitination	NPNYTEFKFPQIKAH CCCCCCCCCCCCCCC	50.32	-
317	S-nitrosylation	PPEAIALCSRLLEYT CHHHHHHHHHHHHHC	1.32	21278135
317	S-nitrosocysteine	PPEAIALCSRLLEYT CHHHHHHHHHHHHHC	1.32	-
356	Phosphorylation	KLPNGRDTPALFNFT CCCCCCCCCHHHEEC	14.75	-
389	Phosphorylation	ARIQAAASPPANATA HHHHHHCCCCCCCCC	27.04	25521595
395	Phosphorylation	ASPPANATAASDTNA CCCCCCCCCCCCCCC	23.67	25619855
398	Phosphorylation	PANATAASDTNAGDR CCCCCCCCCCCCCCC	42.37	25619855
408	Phosphorylation	NAGDRGQTNNAASAS CCCCCCCCCCCHHHH	33.01	20415495
413	Phosphorylation	GQTNNAASASASNST CCCCCCHHHHCCCCC	21.98	25293948
415	Phosphorylation	TNNAASASASNST-- CCCCHHHHCCCCC--	29.72	25293948
417	Phosphorylation	NAASASASNST---- CCHHHHCCCCC----	28.90	25293948
419	Phosphorylation	ASASASNST------ HHHHCCCCC------	32.76	23684622
420	Phosphorylation	SASASNST------- HHHCCCCC-------	47.05	25293948

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
9	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
9	S	Phosphorylation	Kinase	SGK3	Q9ERE3	Uniprot
9	S	Phosphorylation	Kinase	MAP4K5	Q9Y4K4	GPS
9	S	Phosphorylation	Kinase	P70S6K	Q8BSK8	PSP
9	S	Phosphorylation	Kinase	RPS6KB1	P23443	GPS
9	S	Phosphorylation	Kinase	RPS6KA3	P18654	Uniprot
9	S	Phosphorylation	Kinase	PRKCH	P24723	GPS
9	S	Phosphorylation	Kinase	PRKCB	P05771	GPS
9	S	Phosphorylation	Kinase	AKT1	P31749	PSP
9	S	Phosphorylation	Kinase	KAPCA	P05132	PhosphoELM
9	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
9	S	Phosphorylation	Kinase	AKT3	Q9Y243	PSP
9	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
216	Y	Phosphorylation	Kinase	GSK3B	Q9WV60	PSP
216	Y	Phosphorylation	Kinase	FAK	P34152	PSP
356	T	Phosphorylation	Kinase	DYRK1A	Q61214	PSP
389	S	Phosphorylation	Kinase	P38A	Q16539	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
9	S	Phosphorylation	15791206
Inactivated by phosphorylation at Ser-9 (By similarity).
9	S	Phosphorylation	15791206
Phosphorylation of Ser-9 in the hippocampus peaks at CT0, whereas in the liver it peaks at CT12.

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 GSK3B_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
E2F1_MOUSE	E2f1	physical	18367454
AXIN2_MOUSE	Axin2	physical	9554852
AXIN1_MOUSE	Axin1	physical	10318824
CTND1_MOUSE	Ctnnd1	physical	19706605
NF2L2_MOUSE	Nfe2l2	physical	21245377
CTNB1_MOUSE	Ctnnb1	physical	15327768
PSN1_MOUSE	Psen1	physical	11104755
CSN8_MOUSE	Cops8	physical	19576224
MDM2_MOUSE	Mdm2	physical	21738215
P53_MOUSE	Trp53	physical	21738215
NEMO_MOUSE	Ikbkg	physical	12808104
M3K4_MOUSE	Map3k4	physical	17726008
MCL1_MOUSE	Mcl1	physical	22976837
APC_HUMAN	APC	physical	26496610
MTRR_HUMAN	MTRR	physical	26496610
NDUV3_HUMAN	NDUFV3	physical	26496610
KAPCB_HUMAN	PRKACB	physical	26496610
KAP0_HUMAN	PRKAR1A	physical	26496610
TAF5_HUMAN	TAF5	physical	26496610
AP2A_HUMAN	TFAP2A	physical	26496610
AXIN1_HUMAN	AXIN1	physical	26496610
MPZL1_HUMAN	MPZL1	physical	26496610
REPS2_HUMAN	REPS2	physical	26496610
ZER1_HUMAN	ZER1	physical	26496610
ZN273_HUMAN	ZNF273	physical	26496610
RPA34_HUMAN	CD3EAP	physical	26496610
RFIP2_HUMAN	RAB11FIP2	physical	26496610
ZCH14_HUMAN	ZCCHC14	physical	26496610
SO4A1_HUMAN	SLCO4A1	physical	26496610
NT5D3_HUMAN	NT5DC3	physical	26496610
E41LB_HUMAN	EPB41L4B	physical	26496610
BCOR_HUMAN	BCOR	physical	26496610
CDA7L_HUMAN	CDCA7L	physical	26496610
RBM26_HUMAN	RBM26	physical	26496610
NUD18_HUMAN	NUDT18	physical	26496610
SHRPN_HUMAN	SHARPIN	physical	26496610
SYNP2_HUMAN	SYNPO2	physical	26496610
SBSN_HUMAN	SBSN	physical	26496610
TRAF6_MOUSE	Traf6	physical	25828701
M3K7_MOUSE	Map3k7	physical	25828701
TAB1_MOUSE	Tab1	physical	25828701
TAB2_MOUSE	Tab2	physical	25828701
TCAM2_MOUSE	Ticam2	physical	25828701

Drug and Disease Associations

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

Regulatory Network of GSK3B_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"ZNRF1 promotes Wallerian degeneration by degrading AKT to induceGSK3B-dependent CRMP2 phosphorylation."; Wakatsuki S., Saitoh F., Araki T.; Nat. Cell Biol. 13:1415-1423(2011). Cited for: FUNCTION IN PHOSPHORYLATION OF DPYSL2, PHOSPHORYLATION AT SER-9, ANDMUTAGENESIS OF SER-9.	22057101 [Abstract]
"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry."; Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; Mol. Cell. Proteomics 8:904-912(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215, AND MASSSPECTROMETRY.	19131326 [Abstract]
"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain."; Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; J. Proteome Res. 7:311-318(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216 AND SER-219, ANDMASS SPECTROMETRY.	18034455 [Abstract]
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-7; TYR-216 AND SER-219,AND MASS SPECTROMETRY.	17242355 [Abstract]
"Qualitative and quantitative analyses of protein phosphorylation innaive and stimulated mouse synaptosomal preparations."; Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D.,Gerrits B., Panse C., Schlapbach R., Mansuy I.M.; Mol. Cell. Proteomics 6:283-293(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; TYR-216; SER-389AND THR-395, AND MASS SPECTROMETRY.	17114649 [Abstract]
"Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216 AND SER-219, ANDMASS SPECTROMETRY.	17947660 [Abstract]
"Phosphoproteomic analysis of the developing mouse brain."; Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; Mol. Cell. Proteomics 3:1093-1101(2004). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389, AND MASSSPECTROMETRY.	15345747 [Abstract]
"Comprehensive identification of phosphorylation sites in postsynapticdensity preparations."; Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R.,Burlingame A.L.; Mol. Cell. Proteomics 5:914-922(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216, AND MASSSPECTROMETRY.	16452087 [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-216, AND MASSSPECTROMETRY.	15592455 [Abstract]

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