Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZO9S3U)

• DOT Name: ADP-ribosylation factor 5 (ARF5)
• Gene Name: ARF5
• Related Disease: Hepatitis C virus infection
• UniProt ID: ARF5_HUMAN
• PDB ID: 2B6H
• Pfam ID: PF00025
• Sequence:
  MGLTVSALFSRIFGKKQMRILMVGLDAAGKTTILYKLKLGEIVTTIPTIGFNVETVEYKN
  ICFTVWDVGGQDKIRPLWRHYFQNTQGLIFVVDSNDRERVQESADELQKMLQEDELRDAV
  LLVFANKQDMPNAMPVSELTDKLGLQHLRSRTWYVQATCATQGTGLYDGLDWLSHELSKR
• Function: GTP-binding protein involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus; (Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.
• KEGG Pathway: Endocytosis (hsa04144)
• Reactome Pathway:
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	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 increases the expression of ADP-ribosylation factor 5 (ARF5).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribosylation factor 5 (ARF5).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribosylation factor 5 (ARF5).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of ADP-ribosylation factor 5 (ARF5).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of ADP-ribosylation factor 5 (ARF5).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of ADP-ribosylation factor 5 (ARF5).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of ADP-ribosylation factor 5 (ARF5).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ADP-ribosylation factor 5 (ARF5).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of ADP-ribosylation factor 5 (ARF5).	[10]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of ADP-ribosylation factor 5 (ARF5).	[8]

References

• [1] Investigation of the role of GBF1 in the replication of positive-sense single-stranded RNA viruses.J Gen Virol. 2018 Aug;99(8):1086-1096. doi: 10.1099/jgv.0.001099. Epub 2018 Jun 20.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] 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.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] 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.
• [7] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [8] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [9] 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.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.