PMADS

Id:	acc0519
Group:	1sens
Protein:	beta-catenin
Gene Symbol:	CTNNB1
Protein Id:	P35222
Protein Name:	CTNB1_HUMAN
PTM:	phosphorylation
Site:	Tyr654
Site Sequence:	HSRNEGVATYAAAVLFRMSED
Disease Category:	Cancer
Disease:	Thyroid Cancer
Disease Subtype:	anaplastic thyroid carcinoma
Disease Cellline:	SW1736
Disease Info:
Drug:	I131
Drug Info:	"Iodine-131 (I-131) is a radioactive isotope used as a therapeutic agent for hyperthyroidism and thyroid cancer, functioning by emitting beta radiation to selectively destroy overactive thyroid cells or malignant thyroid tissue, with a physical half-life of approximately 8 days and administered orally or intravenously as a radiopharmaceutical. "
Effect:	inhibit
Effect Info:	"ATRA treatment reduced the phosphorylation of beta-catenin (Ser45 and Y654) and GSK-3beta (Ser9), thereby enhancing the sensitivity of undifferentiated thyroid cancer to isotopic therapy."
Note:	Non-conventional drugs
Score:	4.5
Pubmed(PMID):	29344218
Sentence Index:	29344218_0
Sentence:	ATRA increases iodine uptake and inhibits the proliferation and invasiveness of human anaplastic thyroid carcinoma SW1736 cells: Involvement of beta-catenin phosphorylation inhibition.

Sequence & Structure:

MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTSQVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPTNVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSKKEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPALVKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDCLQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEAGGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCAAGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEMAQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLLVRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFVQLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLFRMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEPLGYRQDDPSYRSFHSGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTDL

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
CTNNB1	PRI-724	CBP/beta catenin inhibitor	2	Withdrawn	colorectal adenocarcinoma	ClinicalTrials
CTNNB1	PRI-724	CBP/beta catenin inhibitor	2	Recruiting	cirrhosis of liver	ClinicalTrials
CTNNB1	PRI-724	CBP/beta catenin inhibitor	1	Completed	acute myeloid leukemia	ClinicalTrials
CTNNB1	PRI-724	CBP/beta catenin inhibitor	1	Completed	chronic myelogenous leukemia	ClinicalTrials
CTNNB1	PRI-724	CBP/beta catenin inhibitor	1	Terminated	neoplasm	ClinicalTrials
CTNNB1	PRI-724	CBP/beta catenin inhibitor	1	Completed	pancreatic carcinoma	ClinicalTrials
CTNNB1	PRI-724	CBP/beta catenin inhibitor	1	Completed	pancreatic adenocarcinoma	ClinicalTrials
CTNNB1	PRI-724	CBP/beta catenin inhibitor	1	Completed	Malignant Pancreatic Neoplasm	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

No intensity data of this site,
show all other sites!

CTNNB1-Ser179
Cancer	Intensity
BRCA	-0.962
COAD	0.455
HGSC	1.973
ccRCC	-1.319
GBM	-0.972
HNSC	0.229
LUAD
LUSC
non_ccRCC	-0.072
PDAC	0.409
UCEC	0.257

CTNNB1-Ser191
Cancer	Intensity
BRCA	-1.014
COAD	-0.344
HGSC	0.922
ccRCC	-0.101
GBM	0.311
HNSC	0.693
LUAD	0.681
LUSC	0.136
non_ccRCC	1.119
PDAC	-2.383
UCEC	-0.021

CTNNB1-Ser222
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.549
HNSC
LUAD	-0.77
LUSC	1.445
non_ccRCC
PDAC
UCEC	-0.126

CTNNB1-Ser33
Cancer	Intensity
BRCA
COAD
HGSC	-1.746
ccRCC	0.213
GBM	1.104
HNSC	-0.324
LUAD	-0.011
LUSC
non_ccRCC
PDAC
UCEC	0.764

CTNNB1-Ser37
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.655
GBM	1.477
HNSC	-0.252
LUAD	-0.57
LUSC
non_ccRCC
PDAC
UCEC

CTNNB1-Ser45
Cancer	Intensity
BRCA
COAD	-0.184
HGSC	-1.332
ccRCC
GBM	0.613
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.904

CTNNB1-Ser552
Cancer	Intensity
BRCA	-1.793
COAD	-0.07
HGSC	0.724
ccRCC	1.879
GBM	-0.666
HNSC	0.383
LUAD	0.034
LUSC
non_ccRCC
PDAC	-0.172
UCEC	-0.318

CTNNB1-Ser675
Cancer	Intensity
BRCA	-0.341
COAD	-0.152
HGSC	2.444
ccRCC	-0.185
GBM	0.26
HNSC	0.094
LUAD	-0.329
LUSC	0.129
non_ccRCC	-0.617
PDAC	-1.752
UCEC	0.448

CTNNB1-Thr217
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.319
HNSC	0.802
LUAD	-1.121
LUSC
non_ccRCC
PDAC
UCEC

CTNNB1-Thr40
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

CTNNB1-Thr41
Cancer	Intensity
BRCA
COAD
HGSC	0.385
ccRCC
GBM	0.75
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-1.135

CTNNB1-Thr551
Cancer	Intensity
BRCA
COAD	0.362
HGSC	-1.588
ccRCC
GBM
HNSC	0.735
LUAD	0.046
LUSC	1.147
non_ccRCC
PDAC
UCEC	-0.701

CTNNB1-Thr556
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

CTNNB1-Tyr30
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

CTNNB1-Tyr716
Cancer	Intensity
BRCA
COAD	-0.807
HGSC	1.119
ccRCC
GBM	-0.312
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
Y	654	P	Intestinal cancer	Phosphorylation	21307168
Y	654	U	Idiopathic pulmonary fibrosis	Phosphorylation	19104148
Y	654	U	Nasopharyngeal carcinoma	Phosphorylation	37496925

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:

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DMRdb