Details of Drug Off-Target (DOT)

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

• DOT Name: Ribonuclease P/MRP protein subunit POP5 (POP5)
• Synonyms: hPop5
• Gene Name: POP5
• Related Disease:
  Inflammatory bowel disease
  Prostate cancer
  Prostate carcinoma
  Spinal muscular atrophy
  Ulcerative colitis
• UniProt ID: POP5_HUMAN
• PDB ID: 6AHR; 6AHU
• Pfam ID: PF01900
• Sequence:
  MVRFKHRYLLCELVSDDPRCRLSLDDRVLSSLVRDTIARVHGTFGAAACSIGFAVRYLNA
  YTGIVLLRCRKEFYQLVWSALPFITYLENKGHRYPCFFNTLHVGGTIRTCQKFLIQYNRR
  QLLILLQNCTDEGEREAIQKSVTRSCLLEEEEESGEEAAEAME
• Function: Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway: tRNA processing in the nucleus (R-HSA-6784531)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[2]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[2]
Spinal muscular atrophy	DISTLKOB	Strong	Genetic Variation	[3]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[14]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Ribonuclease P/MRP protein subunit POP5 (POP5).	[15]

References

• [1] DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis.J Crohns Colitis. 2016 Jan;10(1):77-86. doi: 10.1093/ecco-jcc/jjv176. Epub 2015 Sep 28.
• [2] Novel biomarkers for prostate cancer including noncoding transcripts.Am J Pathol. 2009 Dec;175(6):2264-76. doi: 10.2353/ajpath.2009.080868. Epub 2009 Nov 5.
• [3] Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress.Biochem Biophys Res Commun. 2004 Jan 30;314(1):268-76. doi: 10.1016/j.bbrc.2003.12.084.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] 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.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] 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.
• [10] 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.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.