Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZR5JS)

• DOT Name: WW domain-binding protein 2
• Synonyms: WBP-2
• Gene Name: WBP2
• Related Disease:
  Hearing loss, autosomal recessive 107
  Hearing loss, autosomal recessive
• UniProt ID: WBP2_HUMAN
• Pfam ID: PF02893
• Sequence:
  MALNKNHSEGGGVIVNNTESILMSYDHVELTFNDMKNVPEAFKGTKKGTVYLTPYRVIFL
  SKGKDAMQSFMMPFYLMKDCEIKQPVFGANYIKGTVKAEAGGGWEGSASYKLTFTAGGAI
  EFGQRMLQVASQASRGEVPSGAYGYSYMPSGAYVYPPPVANGMYPCPPGYPYPPPPPEFY
  PGPPMMDGAMGYVQPPPPPYPGPMEPPVSGPDVPSTPAAEAKAAEAAASAYYNPGNPHNV
  YMPTSQPPPPPYYPPEDKKTQ
• Function: Acts as a transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation. In presence of estrogen, binds to ESR1-responsive promoters. Required for YAP1 coactivation function on PGR activity. Synergizes with WBP2 in enhancing PGR activity. Modulates expression of post-synaptic scaffolding proteins via regulation of ESR1, ESR2 and PGR.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hearing loss, autosomal recessive 107	DIST8JV7	Moderate	Autosomal recessive	[1]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[1]

2 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 WW domain-binding protein 2.	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of WW domain-binding protein 2.	[11]

11 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 WW domain-binding protein 2.	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of WW domain-binding protein 2.	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of WW domain-binding protein 2.	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of WW domain-binding protein 2.	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of WW domain-binding protein 2.	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of WW domain-binding protein 2.	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of WW domain-binding protein 2.	[9]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of WW domain-binding protein 2.	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of WW domain-binding protein 2.	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of WW domain-binding protein 2.	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of WW domain-binding protein 2.	[13]

References

• [1] Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing. EMBO Mol Med. 2016 Mar 1;8(3):191-207. doi: 10.15252/emmm.201505523.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] 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.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [11] 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.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.