Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBR90RV)

• DOT Name: BRO1 domain-containing protein BROX (BROX)
• Synonyms: BRO1 domain- and CAAX motif-containing protein
• Gene Name: BROX
• UniProt ID: BROX_HUMAN
• PDB ID: 3R9M; 3ULY; 3UM0; 3UM1; 3UM2; 3UM3; 3ZXP
• Pfam ID: PF03097
• Sequence:
  MTHWFHRNPLKATAPVSFNYYGVVTGPSASKICNDLRSSRARLLELFTDLSCNPEMMKNA
  ADSYFSLLQGFINSLDESTQESKLRYIQNFKWTDTLQGQVPSAQQDAVFELISMGFNVAL
  WYTKYASRLAGKENITEDEAKEVHRSLKIAAGIFKHLKESHLPKLITPAEKGRDLESRLI
  EAYVIQCQAEAQEVTIARAIELKHAPGLIAALAYETANFYQKADHTLSSLEPAYSAKWRK
  YLHLKMCFYTAYAYCYHGETLLASDKCGEAIRSLQEAEKLYAKAEALCKEYGETKGPGPT
  VKPSGHLFFRKLGNLVKNTLEKCQRENGFIYFQKIPTEAPQLELKANYGLVEPIPFEFPP
  TSVQWTPETLAAFDLTKRPKDDSTKPKPEEEVKPVKEPDIKPQKDTGCYIS
• Function: Nuclear envelope-associated factor that is involved in the nuclear envelope ruptures during interphase (NERDI) repair, where it is locally recruited by CHMP5 and reduces cytoskeletal stress through its action on SYN2 to help reseal the ruptured membrane.

Molecular Interaction Atlas (MIA) of This DOT

8 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 BRO1 domain-containing protein BROX (BROX).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of BRO1 domain-containing protein BROX (BROX).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BRO1 domain-containing protein BROX (BROX).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BRO1 domain-containing protein BROX (BROX).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of BRO1 domain-containing protein BROX (BROX).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BRO1 domain-containing protein BROX (BROX).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of BRO1 domain-containing protein BROX (BROX).	[8]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of BRO1 domain-containing protein BROX (BROX).	[9]

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 affects the methylation of BRO1 domain-containing protein BROX (BROX).	[7]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.