Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4A8HR3)

• DOT Name: Ribosomal RNA processing protein 1 homolog A (RRP1)
• Synonyms: Novel nuclear protein 1; NNP-1; Nucleolar protein Nop52; RRP1-like protein
• Gene Name: RRP1
• Related Disease:
  Advanced cancer
  Lyme disease
  Neuroblastoma
• UniProt ID: RRP1_HUMAN
• PDB ID: 8FKP; 8FKR; 8FKT; 8FKV
• Pfam ID: PF05997
• Sequence:
  MVSRVQLPPEIQLAQRLAGNEQVTRDRAVRKLRKYIVARTQRAAGGFTHDELLKVWKGLF
  YCMWMQDKPLLQEELGRTISQLVHAFQTTEAQHLFLQAFWQTMNREWTGIDRLRLDKFYM
  LMRMVLNESLKVLKMQGWEERQIEELLELLMTEILHPSSQAPNGVKSHFIEIFLEELTKV
  GAEELTADQNLKFIDPFCRIAARTKDSLVLNNITRGIFETIVEQAPLAIEDLLNELDTQD
  EEVASDSDESSEGGERGDALSQKRSEKPPAGSICRAEPEAGEEQAGDDRDSGGPVLQFDY
  EAVANRLFEMASRQSTPSQNRKRLYKVIRKLQDLAGGIFPEDEIPEKACRRLLEGRRQKK
  TKKQKRLLRLQQERGKGEKEPPSPGMERKRSRRRGVGADPEARAEAGEQPGTAERALLRD
  QPRGRGQRGARQRRRTPRPLTSARAKAANVQEPEKKKKRRE
• Function: Plays a critical role in the generation of 28S rRNA.
• Tissue Specificity: Ubiquitously expressed in fetal and adult tissues.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Lyme disease	DISO70G5	Strong	Biomarker	[2]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ribosomal RNA processing protein 1 homolog A (RRP1).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ribosomal RNA processing protein 1 homolog A (RRP1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ribosomal RNA processing protein 1 homolog A (RRP1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosomal RNA processing protein 1 homolog A (RRP1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribosomal RNA processing protein 1 homolog A (RRP1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosomal RNA processing protein 1 homolog A (RRP1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ribosomal RNA processing protein 1 homolog A (RRP1).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Ribosomal RNA processing protein 1 homolog A (RRP1).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Ribosomal RNA processing protein 1 homolog A (RRP1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ribosomal RNA processing protein 1 homolog A (RRP1).	[12]

References

• [1] Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library.Int J Cancer. 2002 Aug 20;100(6):669-77. doi: 10.1002/ijc.10550.
• [2] Positive and Negative Regulation of Glycerol Utilization by the c-di-GMP Binding Protein PlzA in Borrelia burgdorferi.J Bacteriol. 2018 Oct 23;200(22):e00243-18. doi: 10.1128/JB.00243-18. Print 2018 Nov 15.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [12] 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.