dbPTM

GSK3B_RAT - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	GSK3B_RAT
UniProt AC	P18266
Protein Name	Glycogen synthase kinase-3 beta
Gene Name	Gsk3b
Organism	Rattus norvegicus (Rat).
Sequence Length	420
Subcellular Localization	Cytoplasm. Nucleus. Membrane . 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 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	MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDMWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALFNFTTQELSSNPPLATILIPPHARIQAAASPPANATAASDTNAGDRGQTNNAASASASNST

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
7	Phosphorylation	-MSGRPRTTSFAESC -CCCCCCCCCHHHHC	29.49	27097102
8	Phosphorylation	MSGRPRTTSFAESCK CCCCCCCCCHHHHCC	24.11	27097102
9	Phosphorylation	SGRPRTTSFAESCKP CCCCCCCCHHHHCCC	23.11	17570255
13	Phosphorylation	RTTSFAESCKPVQQP CCCCHHHHCCCCCCC	24.82	28432305
21	Phosphorylation	CKPVQQPSAFGSMKV CCCCCCCCCCCCEEE	31.71	28432305
25	Phosphorylation	QQPSAFGSMKVSRDK CCCCCCCCEEEEECC	14.69	28432305
71	Phosphorylation	NGSFGVVYQAKLCDS CCCCEEEEEEEECCC	10.59	-
205	Acetylation	LCDFGSAKQLVRGEP HCCCCCHHHHHCCCC	45.95	55476401
215	Phosphorylation	VRGEPNVSYICSRYY HCCCCCHHHHHCCCC	18.54	28825834
216	Phosphorylation	RGEPNVSYICSRYYR CCCCCHHHHHCCCCC	11.15	18946175
219	Phosphorylation	PNVSYICSRYYRAPE CCHHHHHCCCCCCCH	17.48	27097102
221	Phosphorylation	VSYICSRYYRAPELI HHHHHCCCCCCCHHH	4.88	-
389	Phosphorylation	ARIQAAASPPANATA HHHHHHCCCCCCCCC	27.04	27097102
395	Phosphorylation	ASPPANATAASDTNA CCCCCCCCCCCCCCC	23.67	28551015
398	Phosphorylation	PANATAASDTNAGDR CCCCCCCCCCCCCCC	42.37	28551015
400	Phosphorylation	NATAASDTNAGDRGQ CCCCCCCCCCCCCCC	25.19	28551015
419	Phosphorylation	ASASASNST------ HHHHCCCCC------	32.76	22673903
420	Phosphorylation	SASASNST------- HHHCCCCC-------	47.05	22673903

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	AKT1	P47196	Uniprot
9	S	Phosphorylation	Kinase	GSK3B	G1T8E2	PSP
9	S	Phosphorylation	Kinase	PKACA	P17612	PSP
9	S	Phosphorylation	Kinase	PRKACA	P27791	GPS
9	S	Phosphorylation	Kinase	CAMK2B	Q13554	PSP
9	S	Phosphorylation	Kinase	CAMK2B	P08413	PSP
9	S	Phosphorylation	Kinase	PRKG1	Q13976	GPS
9	S	Phosphorylation	Kinase	PRKG2	Q64595	GPS
9	S	Phosphorylation	Kinase	RPS6KA1	Q63531	GPS
9	S	Phosphorylation	Kinase	RPS6KB1	P67999	GPS
9	S	Phosphorylation	Kinase	SGK3	Q8R4V0	Uniprot
9	S	Phosphorylation	Kinase	RPS6KA3	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
9	S	Phosphorylation		18424437
Inactivated by phosphorylation at Ser-9 (By similarity).

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_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CTNB1_RAT	Ctnnb1	physical	20623542
APC_RAT	Apc	physical	20623542
KLHL1_HUMAN	KLHL1	physical	16982692
CSK_RAT	Csk	physical	16982692

Drug and Disease Associations

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

Regulatory Network of GSK3B_RAT

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"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-216, AND MUTAGENESIS OF TYR-216.	8382613 [Abstract]

show