Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF7AQK9)

• DOT Name: ADP-ribosylation factor-like protein 5A (ARL5A)
• Gene Name: ARL5A
• Related Disease:
  Autoimmune disease
  Colorectal carcinoma
  Systemic lupus erythematosus
• UniProt ID: ARL5A_HUMAN
• PDB ID: 1Z6Y; 1ZJ6; 2H16; 2H17
• Pfam ID: PF00025
• Sequence:
  MGILFTRIWRLFNHQEHKVIIVGLDNAGKTTILYQFSMNEVVHTSPTIGSNVEEIVINNT
  RFLMWDIGGQESLRSSWNTYYTNTEFVIVVVDSTDRERISVTREELYKMLAHEDLRKAGL
  LIFANKQDVKECMTVAEISQFLKLTSIKDHQWHIQACCALTGEGLCQGLEWMMSRLKIR
• Function: Lacks ADP-ribosylation enhancing activity.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[6]
Selenium	DM25CGV	Approved	Selenium decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[7]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[10]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of ADP-ribosylation factor-like protein 5A (ARL5A).	[11]

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 ADP-ribosylation factor-like protein 5A (ARL5A).	[9]

References

• [1] Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus.Mol Immunol. 2006 Mar;43(9):1497-507. doi: 10.1016/j.molimm.2005.07.039. Epub 2005 Sep 6.
• [2] microRNA-202-3p inhibits cell proliferation by targeting ADP-ribosylation factor-like 5A in human colorectal carcinoma.Clin Cancer Res. 2014 Mar 1;20(5):1146-57. doi: 10.1158/1078-0432.CCR-13-1023. Epub 2013 Dec 10.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] 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.
• [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] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.