Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTILZE44)

• DOT Name: Small ribosomal subunit protein uS17 (RPS11)
• Synonyms: 40S ribosomal protein S11
• Gene Name: RPS11
• Related Disease:
  Advanced cancer
  Cytomegalovirus infection
  Herpes simplex infection
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: RS11_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5A2Q ; 5AJ0 ; 5FLX ; 5LKS ; 5OA3 ; 5T2C ; 5VYC ; 6FEC ; 6G18 ; 6G4S ; 6G4W ; 6G51 ; 6G53 ; 6G5H ; 6G5I ; 6IP5 ; 6IP6 ; 6IP8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6YBW ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZLW ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 6ZMT ; 6ZMW ; 6ZN5 ; 6ZOJ ; 6ZOK ; 6ZON ; 6ZP4 ; 6ZUO ; 6ZV6 ; 6ZVH ; 6ZVJ ; 6ZXD ; 6ZXE ; 6ZXF ; 6ZXG ; 6ZXH ; 7A09 ; 7K5I ; 7MQ8 ; 7MQ9 ; 7MQA ; 7QP6 ; 7QP7 ; 7R4X ; 7TQL ; 7WTS ; 7WTT ; 7WTU ; 7WTV ; 7WTW ; 7WTX ; 7WTZ ; 7WU0 ; 7XNX ; 7XNY ; 8G5Y ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF00366 ; PF16205
• Sequence:
  MADIQTERAYQKQPTIFQNKKRVLLGETGKEKLPRYYKNIGLGFKTPKEAIEGTYIDKKC
  PFTGNVSIRGRILSGVVTKMKMQRTIVIRRDYLHYIRKYNRFEKRHKNMSVHLSPCFRDV
  QIGDIVTVGECRPLSKTVRFNVLKVTKAAGTKKQFQKF
• Function: Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
• 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)
  Translation initiation complex formation (R-HSA-72649)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695)
  Ribosomal scanning and start codon recognition (R-HSA-72702)
  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)
  SARS-CoV-1 modulates host translation machinery (R-HSA-9735869)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Cytomegalovirus infection	DISCEMGC	Strong	Altered Expression	[2]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[3]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[4]
Neoplasm	DISZKGEW	moderate	Altered Expression	[4]

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 uS17 (RPS11).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Small ribosomal subunit protein uS17 (RPS11).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Small ribosomal subunit protein uS17 (RPS11).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein uS17 (RPS11).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Small ribosomal subunit protein uS17 (RPS11).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Small ribosomal subunit protein uS17 (RPS11).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Small ribosomal subunit protein uS17 (RPS11).	[10]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Small ribosomal subunit protein uS17 (RPS11).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Small ribosomal subunit protein uS17 (RPS11).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Small ribosomal subunit protein uS17 (RPS11).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Small ribosomal subunit protein uS17 (RPS11).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein uS17 (RPS11).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Small ribosomal subunit protein uS17 (RPS11).	[17]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Small ribosomal subunit protein uS17 (RPS11).	[18]

References

• [1] Expression profiling of fecal colonocytes for RNA-based screening of colorectal cancer.Int J Oncol. 2007 Nov;31(5):1029-37.
• [2] The interaction between endogenous 30S ribosomal subunit protein S11 and Cucumber mosaic virus LS2b protein affects viral replication, infection and gene silencing suppressor activity.PLoS One. 2017 Aug 14;12(8):e0182459. doi: 10.1371/journal.pone.0182459. eCollection 2017.
• [3] The herpes simplex virus type 1 U(S)11 protein interacts with protein kinase R in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain.J Virol. 2002 Mar;76(5):2029-35. doi: 10.1128/jvi.76.5.2029-2035.2002.
• [4] Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients.PLoS One. 2015 Oct 27;10(10):e0141334. doi: 10.1371/journal.pone.0141334. eCollection 2015.
• [5] 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.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] 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.
• [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] Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia. 2004 Jul-Aug;6(4):354-63. doi: 10.1593/neo.03478.
• [13] Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message. Toxicol Sci. 2010 Aug;116(2):549-61.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [18] 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.