Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCIMSK8)

• DOT Name: Transducin beta-like protein 2 (TBL2)
• Synonyms: WS beta-transducin repeats protein; WS-betaTRP; Williams-Beuren syndrome chromosomal region 13 protein
• Gene Name: TBL2
• Related Disease:
  Beckwith-Wiedemann syndrome
  Bladder cancer
  Gout
  Urinary bladder cancer
  Urinary bladder neoplasm
  Neoplasm of esophagus
• UniProt ID: TBL2_HUMAN
• Pfam ID: PF00400
• Sequence:
  MELSQMSELMGLSVLLGLLALMATAAVARGWLRAGEERSGRPACQKANGFPPDKSSGSKK
  QKQYQRIRKEKPQQHNFTHRLLAAALKSHSGNISCMDFSSNGKYLATCADDRTIRIWSTK
  DFLQREHRSMRANVELDHATLVRFSPDCRAFIVWLANGDTLRVFKMTKREDGGYTFTATP
  EDFPKKHKAPVIDIGIANTGKFIMTASSDTTVLIWSLKGQVLSTINTNQMNNTHAAVSPC
  GRFVASCGFTPDVKVWEVCFGKKGEFQEVVRAFELKGHSAAVHSFAFSNDSRRMASVSKD
  GTWKLWDTDVEYKKKQDPYLLKTGRFEEAAGAAPCRLALSPNAQVLALASGSSIHLYNTR
  RGEKEECFERVHGECIANLSFDITGRFLASCGDRAVRLFHNTPGHRAMVEEMQGHLKRAS
  NESTRQRLQQQLTQAQETLKSLGALKK

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Beckwith-Wiedemann syndrome	DISH15GR	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Gout	DISHC0U7	Strong	Genetic Variation	[3]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[4]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Transducin beta-like protein 2 (TBL2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transducin beta-like protein 2 (TBL2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transducin beta-like protein 2 (TBL2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transducin beta-like protein 2 (TBL2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transducin beta-like protein 2 (TBL2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transducin beta-like protein 2 (TBL2).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transducin beta-like protein 2 (TBL2).	[11]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Transducin beta-like protein 2 (TBL2).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transducin beta-like protein 2 (TBL2).	[14]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Transducin beta-like protein 2 (TBL2).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transducin beta-like protein 2 (TBL2).	[13]

References

• [1] TBL2, a novel transducin family member in the WBS deletion: characterization of the complete sequence, genomic structure, transcriptional variants and the mouse ortholog.Cytogenet Cell Genet. 1999;86(3-4):277-84. doi: 10.1159/000015319.
• [2] The bladder tumor suppressor protein TERE1 (UBIAD1) modulates cell cholesterol: implications for tumor progression.DNA Cell Biol. 2011 Nov;30(11):851-64. doi: 10.1089/dna.2011.1315. Epub 2011 Jul 8.
• [3] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [4] Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.Nat Genet. 2012 Oct;44(10):1090-7. doi: 10.1038/ng.2411. Epub 2012 Sep 9.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [14] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.