Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRMYHI9)

• DOT Name: Homeobox protein Hox-B13 (HOXB13)
• Gene Name: HOXB13
• Related Disease:
  Prostate cancer
  Prostate cancer, hereditary, 9
• UniProt ID: HXB13_HUMAN
• PDB ID: 2CRA; 5EDN; 5EEA; 5EF6; 5EG0; 5EGO; 5NO6; 7PSX
• Pfam ID: PF00046 ; PF12284
• Sequence:
  MEPGNYATLDGAKDIEGLLGAGGGRNLVAHSPLTSHPAAPTLMPAVNYAPLDLPGSAEPP
  KQCHPCPGVPQGTSPAPVPYGYFGGGYYSCRVSRSSLKPCAQAATLAAYPAETPTAGEEY
  PSRPTEFAFYPGYPGTYQPMASYLDVSVVQTLGAPGEPRHDSLLPVDSYQSWALAGGWNS
  QMCCQGEQNPPGPFWKAAFADSSGQHPPDACAFRRGRKKRIPYSKGQLRELEREYAANKF
  ITKDKRRKISAATSLSERQITIWFQNRRVKEKKVLAKVKNSATP
• Function: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds preferentially to methylated DNA.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Definitive	Autosomal dominant	[1]
Prostate cancer, hereditary, 9	DIS4L32Q	Strong	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Homeobox protein Hox-B13 (HOXB13) increases the response to substance of Hydrogen peroxide.	[8]
Paraquat	DMR8O3X	Investigative	Homeobox protein Hox-B13 (HOXB13) increases the response to substance of Paraquat.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Homeobox protein Hox-B13 (HOXB13).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein Hox-B13 (HOXB13).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homeobox protein Hox-B13 (HOXB13).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Homeobox protein Hox-B13 (HOXB13).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Homeobox protein Hox-B13 (HOXB13).	[5]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Homeobox protein Hox-B13 (HOXB13).	[7]

References

• [1] Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012 Jan 12;366(2):141-9. doi: 10.1056/NEJMoa1110000.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [6] 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.
• [7] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [8] Knockdown of the gene for homeobox protein HOXB13 reduces toxicity of oxidative-stress inducers in HEK293 cells. J Toxicol Sci. 2013;38(6):821-2. doi: 10.2131/jts.38.821.