Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEYM6FA)

• DOT Name: ADP-ribosylation factor-like protein 8A (ARL8A)
• Synonyms: ADP-ribosylation factor-like protein 10B; Novel small G protein indispensable for equal chromosome segregation 2
• Gene Name: ARL8A
• Related Disease: Tourette syndrome
• UniProt ID: ARL8A_HUMAN
• PDB ID: 1ZD9; 2H18; 4ILE
• Pfam ID: PF00025
• Sequence:
  MIALFNKLLDWFKALFWKEEMELTLVGLQYSGKTTFVNVIASGQFNEDMIPTVGFNMRKI
  TKGNVTIKLWDIGGQPRFRSMWERYCRGVSAIVYMVDAADQEKIEASKNELHNLLDKPQL
  QGIPVLVLGNKRDLPGALDEKELIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQH
  SKSRRS
• Function: Plays a role in lysosome motility. In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function. May play a role in chromosome segregation.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Salmonella infection (hsa05132)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	No Known	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[10]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of ADP-ribosylation factor-like protein 8A (ARL8A).	[14]

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 ADP-ribosylation factor-like protein 8A (ARL8A).	[13]

References

• [1] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] 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.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.