Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2YBK3W)

• DOT Name: Large ribosomal subunit protein P2 (RPLP2)
• Synonyms: 60S acidic ribosomal protein P2; Renal carcinoma antigen NY-REN-44
• Gene Name: RPLP2
• Related Disease:
  Neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Inflammatory bowel disease
  Pancreas disorder
  Ulcerative colitis
• UniProt ID: RLA2_HUMAN
• PDB ID: 1S4J; 2JDL; 2LBF; 2W1O; 4BEH; 4V6X; 5DDZ; 5GU4
• Pfam ID: PF00428
• Sequence:
  MRYVASYLLAALGGNSSPSAKDIKKILDSVGIEADDDRLNKVISELNGKNIEDVIAQGIG
  KLASVPAGGAVAVSAAPGSAAPAAGSAPAAAEEKKDEKKEESEESDDDMGFGLFD
• Function: Plays an important role in the elongation step of protein synthesis.
• KEGG Pathway:
  Ribosome (hsa03010)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Peptide chain elongation (R-HSA-156902)
  SRP-dependent cotranslational protein targeting to membrane (R-HSA-1799339)
  Viral mRNA Translation (R-HSA-192823)
  Selenocysteine synthesis (R-HSA-2408557)
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  Eukaryotic Translation Termination (R-HSA-72764)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) (R-HSA-975956)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[3]
Pancreas disorder	DISDH7NI	Strong	Biomarker	[4]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PEITC	DMOMN31	Phase 2	Large ribosomal subunit protein P2 (RPLP2) affects the binding of PEITC.	[21]

13 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 Large ribosomal subunit protein P2 (RPLP2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Large ribosomal subunit protein P2 (RPLP2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Large ribosomal subunit protein P2 (RPLP2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Large ribosomal subunit protein P2 (RPLP2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein P2 (RPLP2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Large ribosomal subunit protein P2 (RPLP2).	[10]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Large ribosomal subunit protein P2 (RPLP2).	[11]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Large ribosomal subunit protein P2 (RPLP2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein P2 (RPLP2).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Large ribosomal subunit protein P2 (RPLP2).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Large ribosomal subunit protein P2 (RPLP2).	[18]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Large ribosomal subunit protein P2 (RPLP2).	[19]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Large ribosomal subunit protein P2 (RPLP2).	[20]

4 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 Large ribosomal subunit protein P2 (RPLP2).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Large ribosomal subunit protein P2 (RPLP2).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Large ribosomal subunit protein P2 (RPLP2).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Large ribosomal subunit protein P2 (RPLP2).	[15]

References

• [1] Expression of the ribosomal proteins Rplp0, Rplp1, and Rplp2 in gynecologic tumors.Hum Pathol. 2011 Feb;42(2):194-203. doi: 10.1016/j.humpath.2010.04.020. Epub 2010 Oct 30.
• [2] A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.Nat Genet. 2018 Jul;50(7):968-978. doi: 10.1038/s41588-018-0132-x. Epub 2018 Jun 18.
• [3] 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.
• [4] Upregulation of CD39/NTPDases and P2 receptors in human pancreatic disease.Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G223-30. doi: 10.1152/ajpgi.00259.2006. Epub 2006 Aug 17.
• [5] 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.
• [6] 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.
• [7] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] 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.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [12] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [13] 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.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] 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.
• [16] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [20] Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.
• [21] Identification of potential protein targets of isothiocyanates by proteomics. Chem Res Toxicol. 2011 Oct 17;24(10):1735-43. doi: 10.1021/tx2002806. Epub 2011 Aug 26.