Details of Drug Off-Target (DOT)

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

• DOT Name: Splicing factor C9orf78 (C9ORF78)
• Synonyms: Hepatocellular carcinoma-associated antigen 59
• Gene Name: C9ORF78
• UniProt ID: TLS1_HUMAN
• PDB ID: 7OS2; 8C6J
• Pfam ID: PF07052
• Sequence:
  MPVVRKIFRRRRGDSESEEDEQDSEEVRLKLEETREVQNLRKRPNGVSAVALLVGEKVQE
  ETTLVDDPFQMKTGGMVDMKKLKERGKDKISEEEDLHLGTSFSAETNRRDEDADMMKYIE
  TELKKRKGIVEHEEQKVKPKNAEDCLYELPENIRVSSAKKTEEMLSNQMLSGIPEVDLGI
  DAKIKNIISTEDAKARLLAEQQNKKKDSETSFVPTNMAVNYVQHNRFYHEELNAPIRRNK
  EEPKARPLRVGDTEKPEPERSPPNRKRPANEKATDDYHYEKFKKMNRRY
• Function: Plays a role in pre-mRNA splicing by promoting usage of the upstream 3'-splice site at alternative NAGNAG splice sites; these are sites featuring alternative acceptor motifs separated by only a few nucleotides. May also modulate exon inclusion events. Plays a role in spliceosomal remodeling by displacing WBP4 from SNRNP200 and may act to inhibit SNRNP200 helicase activity. Binds U5 snRNA. Required for proper chromosome segregation. Not required for splicing of shelterin components.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Splicing factor C9orf78 (C9ORF78).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Splicing factor C9orf78 (C9ORF78).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Splicing factor C9orf78 (C9ORF78).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Splicing factor C9orf78 (C9ORF78).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Splicing factor C9orf78 (C9ORF78).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Splicing factor C9orf78 (C9ORF78).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Splicing factor C9orf78 (C9ORF78).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Splicing factor C9orf78 (C9ORF78).	[5]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.