Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTWI90E)

DOT Name B-cell CLL/lymphoma 9-like protein (BCL9L)
Synonyms B-cell lymphoma 9-like protein; BCL9-like protein; Protein BCL9-2
Gene Name BCL9L
Related Disease
Neoplasm ( )
Oral lichen planus ( )
Adenoma ( )
Advanced cancer ( )
Breast carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Hepatocellular carcinoma ( )
Intestinal neoplasm ( )
Matthew-Wood syndrome ( )
Pancreatic cancer ( )
Breast cancer ( )
UniProt ID
BCL9L_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2XB1; 4UP0; 4UP5
Pfam ID
PF11502
Sequence
MRILANKTRLPHPRRREAPGSPPLSPRGHCPPAPAKPMHPENKLTNHGKTGNGGAQSQHQ
NVNQGPTCNVGSKGVGAGNHGAKANQISPSNSSLKNPQAGVPPFSSLKGKVKRDRSVSVD
SGEQREAGTPSLDSEAKEVAPRSKRRCVLERKQPYSGDEWCSGPDSEEDDKPIGATHNCN
VADPAMAAPQLGPGQTTQLPLSESSVPGAPHGPPPGLRPDAPGGGGGGGGVPGKPPSQFV
YVFTTHLANTAAEAVLQGRADSILAYHQQNVPRAKLDQAPKVPPTPEPLPLSTPSAGTPQ
SQPPPLPPPPPPAPGSAPPALPPEGPPEDSSQDLAPNSVGAASTGGGTGGTHPNTPTATT
ANNPLPPGGDPSSAPGPALLGEAAAPGNGQRSLVGSEGLSKEQLEHRERSLQTLRDIERL
LLRSGETEPFLKGPPGGAGEGGPPAQAPPPPQQPPTAPPSGLKKYEEPLQSMISQTQSLG
GPPLEHEVPGHPPGGDMGQQMNMMIQRLGQDSLTPEQVAWRKLQEEYYEEKRRKEEQIGL
HGSRPLQDMMGMGGMMVRGPPPPYHSKPGDQWPPGMGAQLRGPMDVQDPMQLRGGPPFPG
PRFPGNQIQRVPGFGGMQSMPMEVPMNAMQRPVRPGMGWTEDLPPMGGPSNFAQNTMPYP
GGQGEAERFMTPRVREELLRHQLLEKRSMGMQRPLGMAGSGMGQSMEMERMMQAHRQMDP
AMFPGQMAGGEGLAGTPMGMEFGGGRGLLSPPMGQSGLREVDPPMGPGNLNMNMNVNMNM
NMNLNVQMTPQQQMLMSQKMRGPGDLMGPQGLSPEEMARVRAQNSSGVMGGPQKMLMPSQ
FPNQGQQGFSGGQGPYQAMSQDMGNTQDMFSPDQSSMPMSNVGTTRLSHMPLPPASNPPG
TVHSAPNRGLGRRPSDLTISINQMGSPGMGHLKSPTLSQVHSPLVTSPSANLKSPQTPSQ
MVPLPSANPPGPLKSPQVLGSSLSVRSPTGSPSRLKSPSMAVPSPGWVASPKTAMPSPGV
SQNKQPPLNMNSSTTLSNMEQGTLPPSGPRSSSSAPPANPPSGLMNPSLPFTSSPDPTPS
QNPLSLMMTQMSKYAMPSSTPLYHNAIKTIATSDDELLPDRPLLPPPPPPQGSGPGISNS
QPSQMHLNSAAAQSPMGMNLPGQQPLSHEPPPAMLPSPTPLGSNIPLHPNAQGTGGPPQN
SMMMAPGGPDSLNAPCGPVPSSSQMMPFPPRLQQPHGAMAPTGGGGGGPGLQQHYPSGMA
LPPEDLPNQPPGPMPPQQHLMGKAMAGRMGDAYPPGVLPGVASVLNDPELSEVIRPTPTG
IPEFDLSRIIPSEKPSSTLQYFPKSENQPPKAQPPNLHLMNLQNMMAEQTPSRPPNLPGQ
QGVQRGLNMSMCHPGQMSLLGRTGVPPQQGMVPHGLHQGVMSPPQGLMTQQNFMLMKQRG
VGGEVYSQPPHMLSPQGSLMGPPPQQNLMVSHPLRQRSVSLDSQMGYLPAPGGMANLPF
Function Transcriptional regulator that acts as an activator. Promotes beta-catenin transcriptional activity. Plays a role in tumorigenesis. Enhances the neoplastic transforming activity of CTNNB1.
Tissue Specificity
Expressed in breast, ductal and invasive ductal carcinomas of the breast, sporadic colorectal adenomas and carcinomas (at protein level). Expressed in fetal brain. Expressed in lung, amygdala, eye, prostate, pancreatic and prostate cancers, head and neck tumors and embryonal tumor.
Reactome Pathway
Deactivation of the beta-catenin transactivating complex (R-HSA-3769402 )
Formation of the beta-catenin (R-HSA-201722 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Altered Expression [1]
Oral lichen planus DISVEAJA Definitive Biomarker [2]
Adenoma DIS78ZEV Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Breast carcinoma DIS2UE88 Strong Biomarker [4]
Colonic neoplasm DISSZ04P Strong Altered Expression [3]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [5]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [6]
Intestinal neoplasm DISK0GUH Strong Biomarker [3]
Matthew-Wood syndrome DISA7HR7 Strong Altered Expression [7]
Pancreatic cancer DISJC981 Strong Biomarker [7]
Breast cancer DIS7DPX1 moderate Biomarker [4]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of B-cell CLL/lymphoma 9-like protein (BCL9L). [8]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of B-cell CLL/lymphoma 9-like protein (BCL9L). [11]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of B-cell CLL/lymphoma 9-like protein (BCL9L). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of B-cell CLL/lymphoma 9-like protein (BCL9L). [15]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of B-cell CLL/lymphoma 9-like protein (BCL9L). [15]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the phosphorylation of B-cell CLL/lymphoma 9-like protein (BCL9L). [19]
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⏷ Show the Full List of 6 Drug(s)
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of B-cell CLL/lymphoma 9-like protein (BCL9L). [9]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of B-cell CLL/lymphoma 9-like protein (BCL9L). [10]
Menadione DMSJDTY Approved Menadione decreases the expression of B-cell CLL/lymphoma 9-like protein (BCL9L). [12]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of B-cell CLL/lymphoma 9-like protein (BCL9L). [13]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of B-cell CLL/lymphoma 9-like protein (BCL9L). [16]
Milchsaure DM462BT Investigative Milchsaure increases the expression of B-cell CLL/lymphoma 9-like protein (BCL9L). [17]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of B-cell CLL/lymphoma 9-like protein (BCL9L). [18]
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⏷ Show the Full List of 7 Drug(s)

References

1 BCL9L expression in pancreatic neoplasia with a focus on SPN: a possible explanation for the enigma of the benign neoplasia.BMC Cancer. 2016 Aug 18;16:648. doi: 10.1186/s12885-016-2707-1.
2 Identification of the key genes implicated in the transformation of OLP to OSCC using RNA-sequencing.Oncol Rep. 2017 Apr;37(4):2355-2365. doi: 10.3892/or.2017.5487. Epub 2017 Mar 2.
3 BCL9-2 promotes early stages of intestinal tumor progression.Gastroenterology. 2011 Oct;141(4):1359-70, 1370.e1-3. doi: 10.1053/j.gastro.2011.06.039. Epub 2011 Jun 23.
4 The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the -Catenin Coactivator BCL9-2 in Breast Cancer Cells.Mol Cancer Res. 2015 May;13(5):902-12. doi: 10.1158/1541-7786.MCR-14-0180. Epub 2015 Feb 12.
5 Lack of APC somatic mutation is associated with early-onset colorectal cancer in African Americans.Carcinogenesis. 2018 Dec 13;39(11):1331-1341. doi: 10.1093/carcin/bgy122.
6 Wnt status-dependent oncogenic role of BCL9 and BCL9L in hepatocellular carcinoma.Hepatol Int. 2020 May;14(3):373-384. doi: 10.1007/s12072-019-09977-w. Epub 2019 Aug 22.
7 Role of BCL9L in transforming growth factor- (TGF-)-induced epithelial-to-mesenchymal-transition (EMT) and metastasis of pancreatic cancer.Oncotarget. 2016 Nov 8;7(45):73725-73738. doi: 10.18632/oncotarget.12455.
8 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
11 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
12 Vitamin K3 (menadione) suppresses epithelial-mesenchymal-transition and Wnt signaling pathway in human colorectal cancer cells. Chem Biol Interact. 2019 Aug 25;309:108725. doi: 10.1016/j.cbi.2019.108725. Epub 2019 Jun 22.
13 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
14 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
15 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
16 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
18 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
19 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.