Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP8MJAN)

• DOT Name: Protein C3orf33 (C3ORF33)
• Synonyms: Protein AC3-33
• Gene Name: C3ORF33
• UniProt ID: CC033_HUMAN
• Sequence:
  MAGQPAATGSPSADKDGMEPNVVARISQWADDHLRLVRNISTGMAIAGIMLLLRSIRLTS
  KFTSSSDIPVEFIRRNVKLRGRLRRITENGLEIEHIPITLPIIASLRKEPRGALLVKLAG
  VELAETGKAWLQKELKPSQLLWFQLLGKENSALFCYLLVSKGGYFSVNLNEEILRRGLGK
  TVLVKGLKYDSKIYWTVHRNLLKAELTALKKGEGIWKEDSEKESYLEKFKDSWREIWKKD
  SFLKTTGSDFSLKKESYYEKLKRTYEIWKDNMNNCSLILKFRELISRINFRRKG
• Function: [Isoform 2]: Secreted protein may play a role in transcription regulation via the MAPK3/MAPK1 pathway through an unidentified receptor on the plasma membrane.
• Tissue Specificity: Highly expressed in ileocecal tissue and endometrium.

Molecular Interaction Atlas (MIA) of This DOT

12 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 Protein C3orf33 (C3ORF33).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein C3orf33 (C3ORF33).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein C3orf33 (C3ORF33).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein C3orf33 (C3ORF33).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein C3orf33 (C3ORF33).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein C3orf33 (C3ORF33).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein C3orf33 (C3ORF33).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein C3orf33 (C3ORF33).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein C3orf33 (C3ORF33).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein C3orf33 (C3ORF33).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein C3orf33 (C3ORF33).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein C3orf33 (C3ORF33).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein C3orf33 (C3ORF33).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [10] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [11] 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.