Details of Drug Off-Target (DOT)

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

• DOT Name: Large ribosomal subunit protein eL28 (RPL28)
• Synonyms: 60S ribosomal protein L28
• Gene Name: RPL28
• Related Disease:
  Colon cancer
  Colon carcinoma
  Neoplasm
• UniProt ID: RL28_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 ; 7OW7 ; 7QVP ; 7XNX ; 7XNY ; 8A3D ; 8FKQ ; 8FKS ; 8FKU ; 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: PF01778
• Sequence:
  MSAHLQWMVVRNCSSFLIKRNKQTYSTEPNNLKARNSFRYNGLIHRKTVGVEPAADGKGV
  VVVIKRRSGQRKPATSYVRTTINKNARATLSSIRHMIRKNKYRPDLRMAAIRRASAILRS
  QKPVMVKRKRTRPTKSS
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	moderate	Biomarker	[1]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[1]
Neoplasm	DISZKGEW	moderate	Altered Expression	[1]

2 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 Large ribosomal subunit protein eL28 (RPL28).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Large ribosomal subunit protein eL28 (RPL28).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Large ribosomal subunit protein eL28 (RPL28).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Large ribosomal subunit protein eL28 (RPL28).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL28 (RPL28).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Large ribosomal subunit protein eL28 (RPL28).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Large ribosomal subunit protein eL28 (RPL28).	[7]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Large ribosomal subunit protein eL28 (RPL28).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Large ribosomal subunit protein eL28 (RPL28).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Large ribosomal subunit protein eL28 (RPL28).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL28 (RPL28).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Large ribosomal subunit protein eL28 (RPL28).	[13]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Large ribosomal subunit protein eL28 (RPL28).	[14]

References

• [1] Germline variability and tumor expression level of ribosomal protein gene RPL28 are associated with survival of metastatic colorectal cancer patients.Sci Rep. 2019 Sep 10;9(1):13008. doi: 10.1038/s41598-019-49477-3.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
• [9] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [10] 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.
• [11] 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.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.