Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0WYZYG)

• DOT Name: Small ribosomal subunit protein uS19 (RPS15)
• Synonyms: 40S ribosomal protein S15; RIG protein
• Gene Name: RPS15
• Related Disease:
  Advanced cancer
  Anemia
  Diamond-Blackfan anemia
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Insulinoma
  Leukopenia
  Small lymphocytic lymphoma
  T-cell acute lymphoblastic leukaemia
  Adult glioblastoma
  Astrocytoma
  Glioblastoma multiforme
  Glioma
  Neoplasm
• UniProt ID: RS15_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 ; 6YBS ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZLW ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 6ZMT ; 6ZMW ; 6ZN5 ; 6ZOJ ; 6ZOL ; 6ZON ; 6ZP4 ; 6ZUO ; 6ZV6 ; 6ZVH ; 6ZVJ ; 6ZXD ; 6ZXE ; 6ZXF ; 6ZXG ; 6ZXH ; 7A09 ; 7K5I ; 7QP6 ; 7QP7 ; 7R4X ; 7TQL ; 7WTT ; 7WTU ; 7WTV ; 7WTW ; 7WTX ; 7WTZ ; 7WU0 ; 7XNX ; 7XNY ; 8G5Y ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF00203
• Sequence:
  MAEVEQKKKRTFRKFTYRGVDLDQLLDMSYEQLMQLYSARQRRRLNRGLRRKQHSLLKRL
  RKAKKEAPPMEKPEVVKTHLRDMIILPEMVGSMVGVYNGKTFNQVEIKPEMIGHYLGEFS
  ITYKPVKHGRPGIGATHSSRFIPLK
• Function: Component of the small 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)
  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

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Anemia	DISTVL0C	Strong	Genetic Variation	[2]
Diamond-Blackfan anemia	DISI2SNW	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[4]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[4]
Insulinoma	DISIU1JS	Strong	Biomarker	[5]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[2]
Small lymphocytic lymphoma	DIS30POX	Strong	Genetic Variation	[1]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[6]
Astrocytoma	DISL3V18	Limited	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[6]
Glioma	DIS5RPEH	Limited	Genetic Variation	[6]
Neoplasm	DISZKGEW	Limited	Altered Expression	[7]

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 uS19 (RPS15).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Small ribosomal subunit protein uS19 (RPS15).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein uS19 (RPS15).	[9]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Small ribosomal subunit protein uS19 (RPS15).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein uS19 (RPS15).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Small ribosomal subunit protein uS19 (RPS15).	[13]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Small ribosomal subunit protein uS19 (RPS15).	[14]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Small ribosomal subunit protein uS19 (RPS15).	[15]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Small ribosomal subunit protein uS19 (RPS15).	[16]

References

• [1] Ribosomal Lesions Promote Oncogenic Mutagenesis.Cancer Res. 2019 Jan 15;79(2):320-327. doi: 10.1158/0008-5472.CAN-18-1987. Epub 2018 Nov 27.
• [2] A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer.Ann Oncol. 2015 Sep;26(9):1923-1929. doi: 10.1093/annonc/mdv264. Epub 2015 Jun 19.
• [3] Germline Genetic Predisposition to Hematologic Malignancy.J Clin Oncol. 2017 Mar 20;35(9):1018-1028. doi: 10.1200/JCO.2016.70.8644. Epub 2017 Feb 13.
• [4] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [5] Novel gene activated in rat insulinomas.Diabetes. 1986 Oct;35(10):1178-80. doi: 10.2337/diab.35.10.1178.
• [6] Identification of a novel gene product, RIG, that is down-regulated in human glioblastoma.Oncogene. 1997 Mar 6;14(9):1075-81. doi: 10.1038/sj.onc.1200925.
• [7] Rig is a novel Ras-related protein and potential neural tumor suppressor.Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9876-81. doi: 10.1073/pnas.142193799. Epub 2002 Jul 9.
• [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] 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.
• [10] 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.
• [11] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [12] 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.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [14] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [15] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [16] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.