Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT33LM66)

• DOT Name: Large ribosomal subunit protein eL19 (RPL19)
• Synonyms: 60S ribosomal protein L19
• Gene Name: RPL19
• Related Disease:
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Breast neoplasm
  Carcinoma
  Pancreatic tumour
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Yellow fever virus infection
  Colorectal carcinoma
  Diamond-Blackfan anemia
  Neoplasm
• UniProt ID: RL19_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5A2Q ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6SXO ; 6W6L ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7BHP ; 7F5S ; 7OW7 ; 7XNX ; 7XNY ; 8A3D ; 8FKY ; 8FKZ ; 8FL2 ; 8FL3 ; 8FL4 ; 8FL6 ; 8FL7 ; 8FL9 ; 8FLA ; 8FLB ; 8FLC ; 8FLD ; 8FLE ; 8FLF ; 8G5Y ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8IDT ; 8IDY ; 8IE3 ; 8INE ; 8INF ; 8INK ; 8IPD ; 8IPX ; 8IPY ; 8IR1 ; 8IR3 ; 8JDJ ; 8JDK ; 8JDL ; 8JDM
• Pfam ID: PF01280
• Sequence:
  MSMLRLQKRLASSVLRCGKKKVWLDPNETNEIANANSRQQIRKLIKDGLIIRKPVTVHSR
  ARCRKNTLARRKGRHMGIGKRKGTANARMPEKVTWMRRMRILRRLLRRYRESKKIDRHMY
  HSLYLKVKGNVFKNKRILMEHIHKLKADKARKKLLADQAEARRSKTKEARKRREERLQAK
  KEEIIKTLSKEEETKK
• Function: Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
• 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

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[3]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[5]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[3]
Yellow fever virus infection	DISK0X5T	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[7]
Diamond-Blackfan anemia	DISI2SNW	Limited	Biomarker	[8]
Neoplasm	DISZKGEW	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL19 (RPL19).	[9]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Large ribosomal subunit protein eL19 (RPL19).	[10]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Large ribosomal subunit protein eL19 (RPL19).	[10]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Large ribosomal subunit protein eL19 (RPL19).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the expression of Large ribosomal subunit protein eL19 (RPL19).	[11]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Large ribosomal subunit protein eL19 (RPL19).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL19 (RPL19).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large ribosomal subunit protein eL19 (RPL19).	[16]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Large ribosomal subunit protein eL19 (RPL19).	[17]

2 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 eL19 (RPL19).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Large ribosomal subunit protein eL19 (RPL19).	[15]

References

• [1] Identification of ribosomal protein L19 as a novel tumor antigen recognized by autologous cytotoxic T lymphocytes in lung adenocarcinoma.Cancer Sci. 2010 Jan;101(1):46-53. doi: 10.1111/j.1349-7006.2009.01351.x. Epub 2009 Sep 9.
• [2] High-level expression of the ribosomal protein L19 in human breast tumors that overexpress erbB-2.Cancer Res. 1993 Mar 15;53(6):1403-8.
• [3] Ribosomal protein l19 is a prognostic marker for human prostate cancer.Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2061-5. doi: 10.1158/1078-0432.CCR-05-2445.
• [4] The targeted immunocytokine L19-IL2 efficiently inhibits the growth of orthotopic pancreatic cancer.Clin Cancer Res. 2008 Aug 1;14(15):4951-60. doi: 10.1158/1078-0432.CCR-08-0157.
• [5] siRNA knockdown of ribosomal protein gene RPL19 abrogates the aggressive phenotype of human prostate cancer.PLoS One. 2011;6(7):e22672. doi: 10.1371/journal.pone.0022672. Epub 2011 Jul 22.
• [6] Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen.Viruses. 2019 Jan 15;11(1):68. doi: 10.3390/v11010068.
• [7] Faecal ribosomal protein L19 is a genetic prognostic factor for survival in colorectal cancer.J Cell Mol Med. 2008 Oct;12(5B):1936-43. doi: 10.1111/j.1582-4934.2008.00253.x. Epub 2008 Feb 4.
• [8] Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. Br J Haematol. 2013 Aug;162(4):530-6. doi: 10.1111/bjh.12397. Epub 2013 May 30.
• [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] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Differential proteomics identifies PDIA3 as a novel chemoprevention target in human colon cancer cells. Mol Carcinog. 2014 Feb;53 Suppl 1:E11-22. doi: 10.1002/mc.21986. Epub 2012 Dec 19.
• [12] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [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] 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.
• [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] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [17] 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.