Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNOC9L1)

• DOT Name: Inactive ubiquitin thioesterase OTULINL (OTULINL)
• Gene Name: OTULINL
• Related Disease: Asthma
• UniProt ID: OTULL_HUMAN
• PDB ID: 6DRM
• Pfam ID: PF16218
• Sequence:
  MAATRSPTRARERERSGAPAAGSDQVHSWMLATSQALDTVWRMAKGFVMLAVSFLVAAIC
  YFRRLHLYSGHKLKWWIGYLQRKFKRNLSVEAEVDLLSYCAREWKGETPRNKLMRKAYEE
  LFWRHHIKCVRQVRRDNYDALRSVLFQIFSQGISFPSWMKEKDIVKLPEKLLFSQGCNWI
  QQYSFGPEKYTGSNVFGKLRKYVELLKTQWTEFNGIRDYHKRGSMCNTLFSDAILEYKLY
  EALKFIMLYQVTEVYEQMKTKKVIPSLFRLLFSRETSSDPLSFMMNHLNSVGDTCGLEQI
  DMFILGYSLEVKIKVFRLFKFNSRDFEVCYPEEPLRDWPEISLLTENDRHYHIPVF
• Function: Lacks deubiquitinase activity.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Limited	Genetic Variation	[1]

16 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 Inactive ubiquitin thioesterase OTULINL (OTULINL).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Inactive ubiquitin thioesterase OTULINL (OTULINL).	[14]

References

• [1] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] 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.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.