Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ932A3)

DOT Name Catenin beta-1 (CTNNB1)
Synonyms Beta-catenin
Gene Name CTNNB1
Related Disease
Severe intellectual disability-progressive spastic diplegia syndrome ( )
Exudative vitreoretinopathy 7 ( )
Exudative vitreoretinopathy ( )
UniProt ID
CTNB1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1G3J ; 1JDH ; 1JPW ; 1LUJ ; 1P22 ; 1QZ7 ; 1T08 ; 1TH1 ; 2G57 ; 2GL7 ; 2Z6H ; 3DIW ; 3FQN ; 3FQR ; 3SL9 ; 3SLA ; 3TX7 ; 4DJS ; 6M90 ; 6M91 ; 6M92 ; 6M93 ; 6M94 ; 6O9B ; 6O9C ; 6WLX ; 6WNX ; 7AFW ; 7AR4 ; 7UWI ; 7UWO ; 8EI9 ; 8EIA ; 8EIB ; 8EIC
Pfam ID
PF00514
Sequence
MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTS
QVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPT
NVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSK
KEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPAL
VKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDC
LQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEA
GGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCA
AGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEM
AQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLL
VRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFV
QLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLF
RMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEPLGYRQDDPSYRSFH
SGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTD
L
Function
Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle. Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling. Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4. Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts.
Tissue Specificity
Expressed in several hair follicle cell types: basal and peripheral matrix cells, and cells of the outer and inner root sheaths. Expressed in colon. Present in cortical neurons (at protein level). Expressed in breast cancer tissues (at protein level) .
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )
Wnt sig.ling pathway (hsa04310 )
Hippo sig.ling pathway (hsa04390 )
Focal adhesion (hsa04510 )
Adherens junction (hsa04520 )
Sig.ling pathways regulating pluripotency of stem cells (hsa04550 )
Leukocyte transendothelial migration (hsa04670 )
Melanogenesis (hsa04916 )
Thyroid hormone sig.ling pathway (hsa04919 )
Cushing syndrome (hsa04934 )
Alcoholic liver disease (hsa04936 )
Alzheimer disease (hsa05010 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Bacterial invasion of epithelial cells (hsa05100 )
Salmonella infection (hsa05132 )
Hepatitis C (hsa05160 )
Human cytomegalovirus infection (hsa05163 )
Human papillomavirus infection (hsa05165 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
Colorectal cancer (hsa05210 )
Endometrial cancer (hsa05213 )
Prostate cancer (hsa05215 )
Thyroid cancer (hsa05216 )
Basal cell carcinoma (hsa05217 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Arrhythmogenic right ventricular cardiomyopathy (hsa05412 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
Beta-catenin phosphorylation cascade (R-HSA-196299 )
TCF dependent signaling in response to WNT (R-HSA-201681 )
Formation of the beta-catenin (R-HSA-201722 )
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production (R-HSA-3134973 )
Apoptotic cleavage of cell adhesion proteins (R-HSA-351906 )
Deactivation of the beta-catenin transactivating complex (R-HSA-3769402 )
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771 )
Ca2+ pathway (R-HSA-4086398 )
Adherens junctions interactions (R-HSA-418990 )
Binding of TCF/LEF (R-HSA-4411364 )
Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262 )
VEGFR2 mediated vascular permeability (R-HSA-5218920 )
Myogenesis (R-HSA-525793 )
Signaling by GSK3beta mutants (R-HSA-5339716 )
CTNNB1 S33 mutants aren't phosphorylated (R-HSA-5358747 )
CTNNB1 S37 mutants aren't phosphorylated (R-HSA-5358749 )
CTNNB1 S45 mutants aren't phosphorylated (R-HSA-5358751 )
CTNNB1 T41 mutants aren't phosphorylated (R-HSA-5358752 )
RHO GTPases activate IQGAPs (R-HSA-5626467 )
Transcriptional Regulation by VENTX (R-HSA-8853884 )
InlA-mediated entry of Listeria monocytogenes into host cells (R-HSA-8876493 )
RUNX3 regulates WNT signaling (R-HSA-8951430 )
Cardiogenesis (R-HSA-9733709 )
Germ layer formation at gastrulation (R-HSA-9754189 )
Regulation of CDH11 function (R-HSA-9762292 )
Regulation of CDH19 Expression and Function (R-HSA-9764302 )
Formation of paraxial mesoderm (R-HSA-9793380 )
Formation of axial mesoderm (R-HSA-9796292 )
Formation of definitive endoderm (R-HSA-9823730 )
Somitogenesis (R-HSA-9824272 )
CDH11 homotypic and heterotypic interactions (R-HSA-9833576 )
Degradation of beta-catenin by the destruction complex (R-HSA-195253 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Severe intellectual disability-progressive spastic diplegia syndrome DISOUKVZ Definitive Autosomal dominant [1]
Exudative vitreoretinopathy 7 DISTUGQV Strong Autosomal dominant [2]
Exudative vitreoretinopathy DISWN0TG Supportive Autosomal dominant [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 5 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Decitabine DMQL8XJ Approved Catenin beta-1 (CTNNB1) decreases the response to substance of Decitabine. [89]
Progesterone DMUY35B Approved Catenin beta-1 (CTNNB1) increases the Leiomyoma ADR of Progesterone. [90]
Ethanol DMDRQZU Approved Catenin beta-1 (CTNNB1) affects the response to substance of Ethanol. [91]
Prednisolone DMQ8FR2 Approved Catenin beta-1 (CTNNB1) increases the Metabolic disorder ADR of Prednisolone. [90]
MANGIFERIN DMWAF5Z Investigative Catenin beta-1 (CTNNB1) decreases the response to substance of MANGIFERIN. [92]
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80 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Catenin beta-1 (CTNNB1). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Catenin beta-1 (CTNNB1). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Catenin beta-1 (CTNNB1). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Catenin beta-1 (CTNNB1). [6]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Catenin beta-1 (CTNNB1). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Catenin beta-1 (CTNNB1). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Catenin beta-1 (CTNNB1). [9]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Catenin beta-1 (CTNNB1). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Catenin beta-1 (CTNNB1). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Catenin beta-1 (CTNNB1). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Catenin beta-1 (CTNNB1). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the activity of Catenin beta-1 (CTNNB1). [14]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Catenin beta-1 (CTNNB1). [16]
Menadione DMSJDTY Approved Menadione decreases the expression of Catenin beta-1 (CTNNB1). [17]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Catenin beta-1 (CTNNB1). [18]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of Catenin beta-1 (CTNNB1). [19]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Catenin beta-1 (CTNNB1). [20]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Catenin beta-1 (CTNNB1). [12]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Catenin beta-1 (CTNNB1). [22]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of Catenin beta-1 (CTNNB1). [23]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Catenin beta-1 (CTNNB1). [16]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Catenin beta-1 (CTNNB1). [26]
Menthol DMG2KW7 Approved Menthol decreases the expression of Catenin beta-1 (CTNNB1). [27]
Gemcitabine DMSE3I7 Approved Gemcitabine increases the expression of Catenin beta-1 (CTNNB1). [29]
Mifepristone DMGZQEF Approved Mifepristone increases the expression of Catenin beta-1 (CTNNB1). [30]
Sulindac DM2QHZU Approved Sulindac decreases the expression of Catenin beta-1 (CTNNB1). [31]
Palbociclib DMD7L94 Approved Palbociclib increases the expression of Catenin beta-1 (CTNNB1). [32]
Diphenylpyraline DMW4X37 Approved Diphenylpyraline decreases the expression of Catenin beta-1 (CTNNB1). [34]
Imatinib DM7RJXL Approved Imatinib decreases the expression of Catenin beta-1 (CTNNB1). [35]
Dinoprostone DMTYOPD Approved Dinoprostone increases the expression of Catenin beta-1 (CTNNB1). [36]
Olanzapine DMPFN6Y Approved Olanzapine increases the expression of Catenin beta-1 (CTNNB1). [37]
Vitamin A DMJ2AH4 Approved Vitamin A decreases the expression of Catenin beta-1 (CTNNB1). [38]
Adenosine DMM2NSK Approved Adenosine increases the expression of Catenin beta-1 (CTNNB1). [39]
Famotidine DMRL3AB Approved Famotidine increases the expression of Catenin beta-1 (CTNNB1). [37]
Diazoxide DML1538 Approved Diazoxide decreases the expression of Catenin beta-1 (CTNNB1). [42]
Berberine DMC5Q8X Phase 4 Berberine increases the expression of Catenin beta-1 (CTNNB1). [44]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Catenin beta-1 (CTNNB1). [46]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Catenin beta-1 (CTNNB1). [47]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Catenin beta-1 (CTNNB1). [48]
HMPL-004 DM29XGY Phase 3 HMPL-004 decreases the expression of Catenin beta-1 (CTNNB1). [50]
Napabucasin DMDZ6Q3 Phase 3 Napabucasin decreases the expression of Catenin beta-1 (CTNNB1). [29]
EXISULIND DMBY56U Phase 3 EXISULIND decreases the expression of Catenin beta-1 (CTNNB1). [51]
Avastin+/-Tarceva DMA86FL Phase 3 Avastin+/-Tarceva decreases the expression of Catenin beta-1 (CTNNB1). [52]
Thymoquinone DMVDTR2 Phase 2/3 Thymoquinone decreases the expression of Catenin beta-1 (CTNNB1). [53]
Contigoside B DMX9V8K Phase 2/3 Contigoside B affects the expression of Catenin beta-1 (CTNNB1). [54]
CP-461 DMEYMTX Phase 2 CP-461 decreases the expression of Catenin beta-1 (CTNNB1). [55]
Daporinad DMCU74R Phase 2 Daporinad decreases the expression of Catenin beta-1 (CTNNB1). [56]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Catenin beta-1 (CTNNB1). [57]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Catenin beta-1 (CTNNB1). [58]
TAK-114 DMTXE19 Phase 1 TAK-114 decreases the expression of Catenin beta-1 (CTNNB1). [59]
BETULINIC ACID DMBUI2A Phase 1 BETULINIC ACID decreases the expression of Catenin beta-1 (CTNNB1). [60]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Catenin beta-1 (CTNNB1). [29]
Eugenol DM7US1H Patented Eugenol decreases the expression of Catenin beta-1 (CTNNB1). [62]
Flavonoid derivative 1 DMCQP0B Patented Flavonoid derivative 1 decreases the expression of Catenin beta-1 (CTNNB1). [64]
Steroid derivative 1 DMB0NVQ Patented Steroid derivative 1 decreases the expression of Catenin beta-1 (CTNNB1). [12]
CHIR-99021 DMB8MNU Patented CHIR-99021 increases the expression of Catenin beta-1 (CTNNB1). [65]
Tetramethylpyrazine DMC0WNB Discontinued in Phase 2 Tetramethylpyrazine decreases the expression of Catenin beta-1 (CTNNB1). [66]
Celastrol DMWQIJX Preclinical Celastrol decreases the expression of Catenin beta-1 (CTNNB1). [68]
Scriptaid DM9JZ21 Preclinical Scriptaid affects the expression of Catenin beta-1 (CTNNB1). [69]
Dioscin DM5H2W9 Preclinical Dioscin increases the expression of Catenin beta-1 (CTNNB1). [70]
PJ34 DMXO6YH Preclinical PJ34 decreases the expression of Catenin beta-1 (CTNNB1). [71]
Piperlongumine DMIZCOE Preclinical Piperlongumine decreases the expression of Catenin beta-1 (CTNNB1). [72]
Wortmannin DM8EVK5 Terminated Wortmannin decreases the expression of Catenin beta-1 (CTNNB1). [74]
Calphostin C DM9X2D0 Terminated Calphostin C increases the expression of Catenin beta-1 (CTNNB1). [75]
Dizocilpine DMMGYXR Terminated Dizocilpine decreases the expression of Catenin beta-1 (CTNNB1). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Catenin beta-1 (CTNNB1). [76]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Catenin beta-1 (CTNNB1). [77]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Catenin beta-1 (CTNNB1). [19]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Catenin beta-1 (CTNNB1). [78]
Coumarin DM0N8ZM Investigative Coumarin decreases the expression of Catenin beta-1 (CTNNB1). [79]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Catenin beta-1 (CTNNB1). [80]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of Catenin beta-1 (CTNNB1). [57]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Catenin beta-1 (CTNNB1). [82]
D-glucose DMMG2TO Investigative D-glucose increases the expression of Catenin beta-1 (CTNNB1). [83]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Catenin beta-1 (CTNNB1). [13]
Lithium chloride DMHYLQ2 Investigative Lithium chloride increases the expression of Catenin beta-1 (CTNNB1). [84]
Manganese DMKT129 Investigative Manganese decreases the expression of Catenin beta-1 (CTNNB1). [85]
Okadaic acid DM47CO1 Investigative Okadaic acid increases the expression of Catenin beta-1 (CTNNB1). [86]
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos affects the expression of Catenin beta-1 (CTNNB1). [87]
acrolein DMAMCSR Investigative acrolein increases the expression of Catenin beta-1 (CTNNB1). [88]
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⏷ Show the Full List of 80 Drug(s)
9 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Testosterone DM7HUNW Approved Testosterone decreases the phosphorylation of Catenin beta-1 (CTNNB1). [15]
Cannabidiol DM0659E Approved Cannabidiol decreases the phosphorylation of Catenin beta-1 (CTNNB1). [21]
Paclitaxel DMLB81S Approved Paclitaxel decreases the phosphorylation of Catenin beta-1 (CTNNB1). [25]
Hydroxyflutamide DMGIZF5 Approved Hydroxyflutamide decreases the phosphorylation of Catenin beta-1 (CTNNB1). [15]
Bosutinib DMTI8YE Approved Bosutinib decreases the phosphorylation of Catenin beta-1 (CTNNB1). [43]
Rigosertib DMOSTXF Phase 3 Rigosertib decreases the phosphorylation of Catenin beta-1 (CTNNB1). [49]
LY294002 DMY1AFS Phase 1 LY294002 decreases the phosphorylation of Catenin beta-1 (CTNNB1). [21]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Catenin beta-1 (CTNNB1). [61]
SB 203580 DMAET6F Terminated SB 203580 decreases the phosphorylation of Catenin beta-1 (CTNNB1). [21]
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⏷ Show the Full List of 9 Drug(s)
11 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Aspirin DM672AH Approved Aspirin decreases the localization of Catenin beta-1 (CTNNB1). [24]
Topotecan DMP6G8T Approved Topotecan increases the cleavage of Catenin beta-1 (CTNNB1). [28]
Hydrocortisone DMGEMB7 Approved Hydrocortisone increases the localization of Catenin beta-1 (CTNNB1). [33]
Flutamide DMK0O7U Approved Flutamide affects the localization of Catenin beta-1 (CTNNB1). [40]
Hexachlorophene DMLKSE0 Approved Hexachlorophene increases the degradation of Catenin beta-1 (CTNNB1). [41]
Glyceryl trinitrate DMF72W3 Phase 4 Glyceryl trinitrate decreases the localization of Catenin beta-1 (CTNNB1). [45]
PMID26394986-Compound-22 DM43Z1G Patented PMID26394986-Compound-22 affects the localization of Catenin beta-1 (CTNNB1). [63]
KENPAULLONE DMAGVXW Patented KENPAULLONE affects the localization of Catenin beta-1 (CTNNB1). [40]
MG-132 DMKA2YS Preclinical MG-132 decreases the degradation of Catenin beta-1 (CTNNB1). [67]
Nimesulide DMR1NMD Terminated Nimesulide affects the localization of Catenin beta-1 (CTNNB1). [73]
Paraquat DMR8O3X Investigative Paraquat affects the localization of Catenin beta-1 (CTNNB1). [81]
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⏷ Show the Full List of 11 Drug(s)

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