Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFW5IFO)

• DOT Name: Small ribosomal subunit protein eS32 (RPL41)
• Synonyms: 60S ribosomal protein L41; HG12; Large ribosomal subunit protein eL41
• Gene Name: RPL41
• Related Disease:
  Chronic kidney disease
  Diamond-Blackfan anemia
  Hepatocellular carcinoma
  Herpes simplex infection
  Intrahepatic cholangiocarcinoma
  Nasopharyngeal carcinoma
  Neoplasm
  Retinopathy
• UniProt ID: RS32_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5A2Q ; 5AJ0 ; 5LKS ; 5OA3 ; 5VYC ; 6G5H ; 6IP5 ; 6IP6 ; 6IP8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6W6L ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6YBW ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZLW ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 6ZMW ; 6ZOJ ; 6ZOK ; 6ZON ; 6ZP4 ; 6ZVJ ; 7A09 ; 7F5S ; 7K5I ; 7QP6 ; 7QP7 ; 7QVP ; 7R4X ; 7TQL ; 7XNX ; 7XNY ; 8G5Y ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF05162
• Sequence: MRAKWRKKRMRRLKRKRRKMRQRSK
• Function: Component of the small ribosomal subunit (Ref.8) (Probable). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Interacts with the beta subunit of protein kinase CKII and stimulates phosphorylation of DNA topoisomerase II alpha by CKII.
• 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

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Strong	Altered Expression	[1]
Diamond-Blackfan anemia	DISI2SNW	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[4]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[5]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[6]
Neoplasm	DISZKGEW	moderate	Biomarker	[5]
Retinopathy	DISB4B0F	moderate	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	Small ribosomal subunit protein eS32 (RPL41) decreases the response to substance of Artesunate.	[16]

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 Small ribosomal subunit protein eS32 (RPL41).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Small ribosomal subunit protein eS32 (RPL41).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small ribosomal subunit protein eS32 (RPL41).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small ribosomal subunit protein eS32 (RPL41).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Small ribosomal subunit protein eS32 (RPL41).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Small ribosomal subunit protein eS32 (RPL41).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Small ribosomal subunit protein eS32 (RPL41).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Small ribosomal subunit protein eS32 (RPL41).	[15]

References

• [1] Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease.Oxid Med Cell Longev. 2017;2017:9091879. doi: 10.1155/2017/9091879. Epub 2017 Jul 13.
• [2] A Novel 12q13.2-q13.3 Microdeletion Syndrome With Combined Features of Diamond Blackfan Anemia, Pierre Robin Sequence and Klippel Feil Deformity.Front Genet. 2018 Nov 19;9:549. doi: 10.3389/fgene.2018.00549. eCollection 2018.
• [3] Identification of differential expression of genes in hepatocellular carcinoma by suppression subtractive hybridization combined cDNA microarray.Oncol Rep. 2007 Oct;18(4):943-51.
• [4] The virion-packaged endoribonuclease of herpes simplex virus 1 cleaves mRNA in polyribosomes.Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12139-44. doi: 10.1073/pnas.0905828106. Epub 2009 Jul 7.
• [5] Overexpression of PDZK1IP1, EEF1A2 and RPL41 genes in intrahepatic cholangiocarcinoma.Mol Med Rep. 2016 Jun;13(6):4786-90. doi: 10.3892/mmr.2016.5110. Epub 2016 Apr 12.
• [6] Differential expression of a subset of ribosomal protein genes in cell lines derived from human nasopharyngeal epithelium.J Hum Genet. 2010 Feb;55(2):118-20. doi: 10.1038/jhg.2009.124. Epub 2009 Nov 20.
• [7] Mini-peptide RPL41 attenuated retinal neovascularization by inducing degradation of ATF4 in oxygen-induced retinopathy mice.Exp Cell Res. 2018 Aug 15;369(2):243-250. doi: 10.1016/j.yexcr.2018.05.027. Epub 2018 May 24.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] 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.
• [12] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [13] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.