PMADS

Id:	acc3277
Group:	2sens
Protein:	GSK3beta
Gene Symbol:	GSK3B
Protein Id:	P49841
Protein Name:	GSK3B_HUMAN
PTM:	phosphorylation
Site:	Tyr216
Site Sequence:	LVRGEPNVSYICSRYYRAPEL
Disease Category:	Nervous system diseases
Disease:	Alzheimer's Disease
Disease Subtype:
Disease Cellline:	N2aSwe?
Disease Info:
Drug:	Cilostazol + resveratrol
Drug Info:	"Cilostazol is a medication used to treat intermittent claudication by improving blood flow. \| Resveratrol is a natural compound with potential health benefits, including antioxidant and anti - inflammatory properties. "
Effect:	modulate
Effect Info:	Cilostazol reduces the increased expression of GSK3β P-Tyr216.
Note:
Score:	4.0
Pubmed(PMID):	24254769
Sentence Index:	24254769_1-2
Sentence:	"beta-Amyloid (Abeta) deposits and hyperphosphorylated tau aggregates are the chief hallmarks in the Alzheimer's disease (AD) brains, but the strategies for controlling these pathological events remain elusive. We hypothesized that CK2-coupled SIRT1 activation stimulated by cilostazol suppresses tau acetylation (Ac-tau) and tau phosphorylation (P-tau) by inhibiting activation of P300 and GSK3beta."

Sequence & Structure:

MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALFNFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	-	bipolar I disorder	DailyMed DailyMed DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Completed	bipolar I disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Withdrawn	bipolar I disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Unknown status	bipolar I disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CITRATE	Glycogen synthase kinase-3 inhibitor	4	-	bipolar I disorder	DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Completed	depressive disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Terminated	depressive disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Unknown status	depressive disorder	ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	-	major depressive disorder	DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Recruiting	depressive disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Completed	bipolar disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Unknown status	bipolar disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	-	bipolar disorder	DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed DailyMed
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Recruiting	bipolar disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Terminated	bipolar disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	4	Withdrawn	bipolar disorder	ClinicalTrials ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	stroke	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Recruiting	internal carotid artery stenosis	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	aggressive behavior	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Recruiting	carotid artery disease	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Active, not recruiting	autism spectrum disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	conduct disorder	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Terminated	anxiety	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	treatment resistant depression	ClinicalTrials
GSK3B	LITHIUM CARBONATE	Glycogen synthase kinase-3 inhibitor	3	Completed	bipolar I disorder	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

GSK3B-Tyr216
Cancer	Intensity
BRCA	-0.529
COAD	-0.006
HGSC	1.642
ccRCC	-1.621
GBM	0.231
HNSC
LUAD	-0.103
LUSC	0.986
non_ccRCC
PDAC
UCEC	-0.6

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
Y	216	D	Dementia with Lewy bodies	Phosphorylation	27609071
Y	216	D	Parkinson's disease	Phosphorylation	27609071
Y	216	D	Squamous cell carcinoma	Phosphorylation	18606491
Y	216	U	Breast cancer/tumor/carcinoma	Phosphorylation	23565238
Y	216	U	Fibrosarcoma	Phosphorylation	31808966
Y	216	U	Pancreatic cancer/carcinoma/adenocarcinoma	Phosphorylation	23408967
Y	216	U	Synovial sarcoma	Phosphorylation	31808966
Y	216	U	Neuroblastoma	Phosphorylation	24349301
Y	216	U	Sporadic inclusion body myositis	Phosphorylation	19878439

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb