Details of Drug Off-Target (DOT)

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

• DOT Name: Bridging integrator 3 (BIN3)
• Gene Name: BIN3
• Related Disease: Parkinson disease
• UniProt ID: BIN3_HUMAN
• Pfam ID: PF03114
• Sequence:
  MSWIPFKIGQPKKQIVPKTVERDFEREYGKLQQLEEQTRRLQKDMKKSTDADLAMSKSAV
  KISLDLLSNPLCEQDQDLLNMVTALDTAMKRMDAFNQEKVNQIQKTVIEPLKKFGSVFPS
  LNMAVKRREQALQDYRRLQAKVEKYEEKEKTGPVLAKLHQAREELRPVREDFEAKNRQLL
  EEMPRFYGSRLDYFQPSFESLIRAQVVYYSEMHKIFGDLSHQLDQPGHSDEQRERENEAK
  LSELRALSIVADD
• Function: Involved in cytokinesis and septation where it has a role in the localization of F-actin.
• Tissue Specificity: Ubiquitously expressed except in brain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Bridging integrator 3 (BIN3) affects the response to substance of Etoposide.	[9]
Mitomycin	DMH0ZJE	Approved	Bridging integrator 3 (BIN3) affects the response to substance of Mitomycin.	[9]

3 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 Bridging integrator 3 (BIN3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Bridging integrator 3 (BIN3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Bridging integrator 3 (BIN3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bridging integrator 3 (BIN3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Bridging integrator 3 (BIN3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Bridging integrator 3 (BIN3).	[5]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Bridging integrator 3 (BIN3).	[6]

References

• [1] Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance.Front Genet. 2019 Jan 25;9:701. doi: 10.3389/fgene.2018.00701. eCollection 2018.
• [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] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.