Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWPNZF9)

• DOT Name: E3 ubiquitin-protein ligase RNF183 (RNF183)
• Synonyms: EC 2.3.2.27
• Gene Name: RNF183
• Related Disease:
  Colorectal carcinoma
  Inflammatory bowel disease
  Irritable bowel syndrome
  Neoplasm
• UniProt ID: RN183_HUMAN
• EC Number: 2.3.2.27
• Sequence:
  MAEQQGRELEAECPVCWNPFNNTFHTPKMLDCCHSFCVECLAHLSLVTPARRRLLCPLCR
  QPTVLASGQPVTDLPTDTAMLALLRLEPHHVILEGHQLCLKDQPKSRYFLRQPQVYTLDL
  GPQPGGQTGPPPDTASATVSTPILIPSHHSLRECFRNPQFRIFAYLMAVILSVTLLLIFS
  IFWTKQFLWGVG
• Function: Acts as an E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Triggers apoptosis in response to prolonged ER stress by mediating the polyubiquitination and subsequent proteasomal degradation of BCL2L1. May collaborate with FATE1 to restrain BIK protein levels thus regulating apoptotic signaling.
• Tissue Specificity: Kidney and testis.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[2]
Irritable bowel syndrome	DIS27206	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of E3 ubiquitin-protein ligase RNF183 (RNF183).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of E3 ubiquitin-protein ligase RNF183 (RNF183).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of E3 ubiquitin-protein ligase RNF183 (RNF183).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of E3 ubiquitin-protein ligase RNF183 (RNF183).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of E3 ubiquitin-protein ligase RNF183 (RNF183).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of E3 ubiquitin-protein ligase RNF183 (RNF183).	[8]
Malathion	DMXZ84M	Approved	Malathion increases the expression of E3 ubiquitin-protein ligase RNF183 (RNF183).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of E3 ubiquitin-protein ligase RNF183 (RNF183).	[10]

References

• [1] Synthetic lethal short hairpin RNA screening reveals that ring finger protein 183 confers resistance to trametinib in colorectal cancer cells.Chin J Cancer. 2017 Jul 31;36(1):63. doi: 10.1186/s40880-017-0228-1.
• [2] E3 Ubiquitin ligase RNF183 Is a Novel Regulator in Inflammatory Bowel Disease.J Crohns Colitis. 2016 Jun;10(6):713-25. doi: 10.1093/ecco-jcc/jjw023. Epub 2016 Jan 27.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.