Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLQVY1Z)

• DOT Name: Large ribosomal subunit protein eL30 (RPL30)
• Synonyms: 60S ribosomal protein L30
• Gene Name: RPL30
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Medulloblastoma
  Myopathy
• UniProt ID: RL30_HUMAN
• PDB ID: 3VI6 ; 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 ; 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: PF01248
• Sequence:
  MVAAKKTKKSLESINSRLQLVMKSGKYVLGYKQTLKMIRQGKAKLVILANNCPALRKSEI
  EYYAMLAKTGVHHYSGNNIELGTACGKYYRVCTLAIIDPGDSDIIRSMPEQTGEK
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[3]
Myopathy	DISOWG27	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Large ribosomal subunit protein eL30 (RPL30).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Large ribosomal subunit protein eL30 (RPL30).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Large ribosomal subunit protein eL30 (RPL30).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL30 (RPL30).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Large ribosomal subunit protein eL30 (RPL30).	[10]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Large ribosomal subunit protein eL30 (RPL30).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Large ribosomal subunit protein eL30 (RPL30).	[12]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Large ribosomal subunit protein eL30 (RPL30).	[11]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Large ribosomal subunit protein eL30 (RPL30).	[11]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Large ribosomal subunit protein eL30 (RPL30).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Large ribosomal subunit protein eL30 (RPL30).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large ribosomal subunit protein eL30 (RPL30).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Large ribosomal subunit protein eL30 (RPL30).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Large ribosomal subunit protein eL30 (RPL30).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Large ribosomal subunit protein eL30 (RPL30).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Large ribosomal subunit protein eL30 (RPL30).	[16]

References

• [1] Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements.BMC Syst Biol. 2008 Aug 10;2:72. doi: 10.1186/1752-0509-2-72.
• [2] Identification of the antigens predominantly reacted with serum from patients with hepatocellular carcinoma.Cancer. 2003 May 15;97(10):2474-9. doi: 10.1002/cncr.11374.
• [3] Medulloblastoma outcome is adversely associated with overexpression of EEF1D, RPL30, and RPS20 on the long arm of chromosome 8.BMC Cancer. 2006 Sep 12;6:223. doi: 10.1186/1471-2407-6-223.
• [4] Stable reference genes for expression studies in breast muscle of normal and white striping-affected chickens.Mol Biol Rep. 2020 Jan;47(1):45-53. doi: 10.1007/s11033-019-05103-z. Epub 2019 Oct 3.
• [5] 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.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [11] 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.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [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] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] 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.
• [17] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.