Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GUFIG)

• DOT Name: eIF5-mimic protein 2 (BZW1)
• Synonyms: Basic leucine zipper and W2 domain-containing protein 1; Protein Orf
• Gene Name: BZW1
• Related Disease:
  Colorectal carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Melanoma
  Non-small-cell lung cancer
• UniProt ID: 5MP2_HUMAN
• Pfam ID: PF02020
• Sequence:
  MNNQKQQKPTLSGQRFKTRKRDEKERFDPTQFQDCIIQGLTETGTDLEAVAKFLDASGAK
  LDYRRYAETLFDILVAGGMLAPGGTLADDMMRTDVCVFAAQEDLETMQAFAQVFNKLIRR
  YKYLEKGFEDEVKKLLLFLKGFSESERNKLAMLTGVLLANGTLNASILNSLYNENLVKEG
  VSAAFAVKLFKSWINEKDINAVAASLRKVSMDNRLMELFPANKQSVEHFTKYFTEAGLKE
  LSEYVRNQQTIGARKELQKELQEQMSRGDPFKDIILYVKEEMKKNNIPEPVVIGIVWSSV
  MSTVEWNKKEELVAEQAIKHLKQYSPLLAAFTTQGQSELTLLLKIQEYCYDNIHFMKAFQ
  KIVVLFYKAEVLSEEPILKWYKDAHVAKGKSVFLEQMKKFVEWLKNAEEESESEAEEGD
• Function: Translation initiation regulator which represses repeat-associated non-AUG (RAN) initiated translation probably by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function. Enhances histone H4 gene transcription but does not seem to bind DNA directly.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of eIF5-mimic protein 2 (BZW1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of eIF5-mimic protein 2 (BZW1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of eIF5-mimic protein 2 (BZW1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of eIF5-mimic protein 2 (BZW1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of eIF5-mimic protein 2 (BZW1).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of eIF5-mimic protein 2 (BZW1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of eIF5-mimic protein 2 (BZW1).	[10]
Aspirin	DM672AH	Approved	Aspirin increases the expression of eIF5-mimic protein 2 (BZW1).	[11]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of eIF5-mimic protein 2 (BZW1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of eIF5-mimic protein 2 (BZW1).	[13]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of eIF5-mimic protein 2 (BZW1).	[14]

References

• [1] Long interspersed nucleotide acid element-1 ORF-1 protein promotes proliferation and invasion of human colorectal cancer LoVo cells through enhancing ETS-1 activity.Genet Mol Res. 2014 Apr 14;13(3):6981-94. doi: 10.4238/2014.April.14.13.
• [2] Overexpression of BZW1 is an independent poor prognosis marker and its down-regulation suppresses lung adenocarcinoma metastasis.Sci Rep. 2019 Oct 10;9(1):14624. doi: 10.1038/s41598-019-50874-x.
• [3] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [8] 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.
• [9] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [10] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [11] 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.
• [12] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.