Details of Drug Off-Target (DOT)

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

• DOT Name: Ribonuclease P protein subunit p38 (RPP38)
• Synonyms: RNaseP protein p38
• Gene Name: RPP38
• Related Disease:
  Melanoma
  Systemic sclerosis
• UniProt ID: RPP38_HUMAN
• PDB ID: 6AHR; 6AHU
• Pfam ID: PF01248
• Sequence:
  MAAAPQAPGRGSLRKTRPLVVKTSLNNPYIIRWSALESEDMHFILQTLEDRLKAIGLQKI
  EDKKKKNKTPFLKKESREKCSIAVDISENLKEKKTDAKQQVSGWTPAHVRKQLAIGVNEV
  TRALERRELLLVLVCKSVKPAMITSHLIQLSLSRSVPACQVPRLSERIAPVIGLKCVLAL
  AFKKNTTDFVDEVRAIIPRVPSLSVPWLQDRIEDSGENLETEPLESQDRELLDTSFEDLS
  KPKRKLADGRQASVTLQPLKIKKLIPNPNKIRKPPKSKKATPK
• Function: Component of ribonuclease P, a ribonucleoprotein 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:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  tRNA processing in the nucleus (R-HSA-6784531)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Strong	Biomarker	[1]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ribonuclease P protein subunit p38 (RPP38).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribonuclease P protein subunit p38 (RPP38).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ribonuclease P protein subunit p38 (RPP38).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ribonuclease P protein subunit p38 (RPP38).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ribonuclease P protein subunit p38 (RPP38).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ribonuclease P protein subunit p38 (RPP38).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ribonuclease P protein subunit p38 (RPP38).	[7]

References

• [1] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [2] Autoantibodies to a novel Rpp38 (Th/To) derived B-cell epitope are specific for systemic sclerosis and associate with a distinct clinical phenotype.Rheumatology (Oxford). 2019 Oct 1;58(10):1784-1793. doi: 10.1093/rheumatology/kez123.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [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] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] 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.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.