Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZZW7TK)

• DOT Name: Large ribosomal subunit protein eL14 (RPL14)
• Synonyms: 60S ribosomal protein L14; CAG-ISL 7
• Gene Name: RPL14
• Related Disease:
  Clear cell renal carcinoma
  Hepatocellular carcinoma
  Papillary renal cell carcinoma
  Parkinson disease
  Renal cell carcinoma
  Squamous cell carcinoma
  Non-insulin dependent diabetes
  Head-neck squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Non-small-cell lung cancer
• UniProt ID: RL14_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6W6L ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7BHP ; 7F5S ; 7QVP ; 7XNX ; 7XNY ; 8FKP ; 8FKQ ; 8FKR ; 8FKS ; 8FKT ; 8FKU ; 8FKV ; 8FKW ; 8FKX ; 8FKY ; 8FKZ ; 8FL0 ; 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: PF01929
• Sequence:
  MVFRRFVEVGRVAYVSFGPHAGKLVAIVDVIDQNRALVDGPCTQVRRQAMPFKCMQLTDF
  ILKFPHSAHQKYVRQAWQKADINTKWAATRWAKKIEARERKAKMTDFDRFKVMKAKKMRN
  RIIKNEVKKLQKAALLKASPKKAPGTKGTAAAAAAAAAAKVPAKKITAASKKAPAQKVPA
  QKATGQKAAPAPKAQKGQKAPAQKAPAPKASGKKA
• 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

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[1]
Parkinson disease	DISQVHKL	Strong	Biomarker	[3]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[4]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[5]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Genetic Variation	[6]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[6]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[6]
Lung neoplasm	DISVARNB	Limited	Genetic Variation	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Large ribosomal subunit protein eL14 (RPL14).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Large ribosomal subunit protein eL14 (RPL14).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Large ribosomal subunit protein eL14 (RPL14).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Large ribosomal subunit protein eL14 (RPL14).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large ribosomal subunit protein eL14 (RPL14).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein eL14 (RPL14).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL14 (RPL14).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Large ribosomal subunit protein eL14 (RPL14).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Large ribosomal subunit protein eL14 (RPL14).	[14]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Large ribosomal subunit protein eL14 (RPL14).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Large ribosomal subunit protein eL14 (RPL14).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein eL14 (RPL14).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL14 (RPL14).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Large ribosomal subunit protein eL14 (RPL14).	[20]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Large ribosomal subunit protein eL14 (RPL14).	[22]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Large ribosomal subunit protein eL14 (RPL14).	[23]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Large ribosomal subunit protein eL14 (RPL14).	[16]

References

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• [2] Identification of differential expression of genes in hepatocellular carcinoma by suppression subtractive hybridization combined cDNA microarray.Oncol Rep. 2007 Oct;18(4):943-51.
• [3] Quantitative proteomics of a presymptomatic A53T alpha-synuclein Drosophila model of Parkinson disease.Mol Cell Proteomics. 2008 Jul;7(7):1191-203. doi: 10.1074/mcp.M700467-MCP200. Epub 2008 Mar 18.
• [4] Alteration of RPL14 in squamous cell carcinomas and preneoplastic lesions of the esophagus.Gene. 2006 Jan 17;366(1):161-8. doi: 10.1016/j.gene.2005.09.025. Epub 2005 Nov 28.
• [5] Identification of trinucleotide repeat-containing genes in human pancreatic islets.Diabetes. 1996 Feb;45(2):157-64. doi: 10.2337/diab.45.2.157.
• [6] Trinucleotide repeat length variation in the human ribosomal protein L14 gene (RPL14): localization to 3p21.3 and loss of heterozygosity in lung and oral cancers.Mutat Res. 1998 Nov;406(1):9-23. doi: 10.1016/s1383-5726(98)00006-5.
• [7] Molecular analysis in combination with iodine staining may contribute to the risk prediction of esophageal squamous cell carcinoma.J Cancer Res Clin Oncol. 2008 Mar;134(3):307-15. doi: 10.1007/s00432-007-0269-y. Epub 2007 Aug 14.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [12] 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.
• [13] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [14] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [15] 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.
• [16] Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
• [17] 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.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] 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.
• [22] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [23] 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.