Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT9CVZR)

• DOT Name: Protein C1orf43 (C1ORF43)
• Synonyms: Hepatitis C virus NS5A-transactivated protein 4; HCV NS5A-transactivated protein 4; Protein NICE-3; S863-3
• Gene Name: C1ORF43
• Related Disease: Hepatocellular carcinoma
• UniProt ID: CA043_HUMAN
• Pfam ID: PF07406
• Sequence:
  MASGSNWLSGVNVVLVMAYGSLVFVLLFIFVKRQIMRFAMKSRRGPHVPVGHNAPKDLKE
  EIDIRLSRVQDIKYEPQLLADDDARLLQLETQGNQSCYNYLYRMKALDAIRTSEIPFHSE
  GRHPRSLMGKNFRSYLLDLRNTSTPFKGVRKALIDTLLDGYETARYGTGVFGQNEYLRYQ
  EALSELATAVKARIGSSQRHHQSAAKDLTQSPEVSPTTIQVTYLPSSQKSKRAKHFLELK
  SFKDNYNTLESTL
• Function: General regulator of phagocytosis. Required to uptake Gram negative bacterium by macrophages.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein C1orf43 (C1ORF43).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein C1orf43 (C1ORF43).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein C1orf43 (C1ORF43).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Protein C1orf43 (C1ORF43).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein C1orf43 (C1ORF43).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Protein C1orf43 (C1ORF43).	[7]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Protein C1orf43 (C1ORF43).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein C1orf43 (C1ORF43).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein C1orf43 (C1ORF43).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein C1orf43 (C1ORF43).	[11]

References

• [1] Up-regulation of NICE-3 as a novel EDC gene could contribute to human hepatocellular carcinoma.Asian Pac J Cancer Prev. 2012;13(9):4363-8. doi: 10.7314/apjcp.2012.13.9.4363.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [6] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [7] 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.
• [8] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [9] 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.
• [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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.