Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4WCQBE)

• DOT Name: Large ribosomal subunit protein uL30 (RPL7)
• Synonyms: 60S ribosomal protein L7
• Gene Name: RPL7
• Related Disease: Brucellosis
• UniProt ID: RL7_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 ; 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: PF00327 ; PF08079
• Sequence:
  MEGVEEKKKEVPAVPETLKKKRRNFAELKIKRLRKKFAQKMLRKARRKLIYEKAKHYHKE
  YRQMYRTEIRMARMARKAGNFYVPAEPKLAFVIRIRGINGVSPKVRKVLQLLRLRQIFNG
  TFVKLNKASINMLRIVEPYIAWGYPNLKSVNELIYKRGYGKINKKRIALTDNALIARSLG
  KYGIICMEDLIHEIYTVGKRFKEANNFLWPFKLSSPRGGMKKKTTHFVEGGDAGNREDQI
  NRLIRRMN
• Function: Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Binds to G-rich structures in 28S rRNA and in mRNAs. Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs.
• 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

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brucellosis	DISEAYGH	Disputed	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	Large ribosomal subunit protein uL30 (RPL7) decreases the response to substance of Artesunate.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Large ribosomal subunit protein uL30 (RPL7).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Large ribosomal subunit protein uL30 (RPL7).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Large ribosomal subunit protein uL30 (RPL7).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[12]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Large ribosomal subunit protein uL30 (RPL7).	[13]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Large ribosomal subunit protein uL30 (RPL7).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Large ribosomal subunit protein uL30 (RPL7).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein uL30 (RPL7).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Large ribosomal subunit protein uL30 (RPL7).	[19]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Large ribosomal subunit protein uL30 (RPL7).	[20]

2 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 uL30 (RPL7).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Large ribosomal subunit protein uL30 (RPL7).	[16]

References

• [1] Production and targeting of the Brucella abortus antigen L7/L12 in Lactococcus lactis: a first step towards food-grade live vaccines against brucellosis.Appl Environ Microbiol. 2002 Feb;68(2):910-6. doi: 10.1128/AEM.68.2.910-916.2002.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene. 2001 Jan 10;262(1-2):207-14. doi: 10.1016/s0378-1119(00)00530-8.
• [7] 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.
• [8] 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.
• [9] Gene expression profile changes in NB4 cells induced by arsenic trioxide. Acta Pharmacol Sin. 2003 Jul;24(7):646-50.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] 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.
• [13] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [14] 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.
• [15] Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message. Toxicol Sci. 2010 Aug;116(2):549-61.
• [16] 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.
• [17] 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.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [21] Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.