Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8052R)

• DOT Name: Small ribosomal subunit protein uS10 (RPS20)
• Synonyms: 40S ribosomal protein S20
• Gene Name: RPS20
• Related Disease:
  Asthma
  Atopic dermatitis
  Autoimmune hepatitis
  B-cell lymphoma
  Central diabetes insipidus
  Colon cancer
  Colon carcinoma
  Familial adenomatous polyposis
  Follicular lymphoma
  Medulloblastoma
  Gastric cancer
  Glioblastoma multiforme
  Diamond-Blackfan anemia
  Familial colorectal cancer type X
  Colorectal carcinoma
  Hereditary nonpolyposis colon cancer
  Lynch syndrome
  Lynch syndrome 1
  Lynch syndrome 2
  Systemic lupus erythematosus
• UniProt ID: RS20_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5A2Q ; 5AJ0 ; 5FLX ; 5LKS ; 5OA3 ; 5T2C ; 5VYC ; 6FEC ; 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 ; 7XNX ; 7XNY ; 8G5Y ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF00338
• Sequence:
  MAFKDTGKTPVEPEVAIHRIRITLTSRNVKSLEKVCADLIRGAKEKNLKVKGPVRMPTKT
  LRITTRKTPCGEGSKTWDRFQMRIHKRLIDLHSPSEIVKQITSISIEPGVEVEVTIADA
• 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

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Strong	Biomarker	[1]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[1]
Autoimmune hepatitis	DISOX03Q	Strong	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[3]
Central diabetes insipidus	DISJ4P9O	Strong	Genetic Variation	[4]
Colon cancer	DISVC52G	Strong	Genetic Variation	[5]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[5]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[6]
Follicular lymphoma	DISVEUR6	Strong	Genetic Variation	[3]
Medulloblastoma	DISZD2ZL	Strong	Genetic Variation	[7]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[8]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[9]
Diamond-Blackfan anemia	DISI2SNW	Supportive	Autosomal dominant	[10]
Familial colorectal cancer type X	DISEBNIA	Supportive	Autosomal dominant	[5]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[6]
Hereditary nonpolyposis colon cancer	DISPA49R	Limited	Autosomal dominant	[11]
Lynch syndrome	DIS3IW5F	Limited	Autosomal dominant	[12]
Lynch syndrome 1	DISSABLZ	Limited	Biomarker	[13]
Lynch syndrome 2	DISRLYU1	Limited	Biomarker	[13]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[16]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[17]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[18]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Small ribosomal subunit protein uS10 (RPS20).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[23]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[24]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[25]
torin 1	DMZD0NA	Investigative	torin 1 decreases the expression of Small ribosomal subunit protein uS10 (RPS20).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Small ribosomal subunit protein uS10 (RPS20).	[20]

References

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• [2] Novel autoimmune hepatitis-specific autoantigens identified using protein microarray technology.J Proteome Res. 2010 Jan;9(1):30-9. doi: 10.1021/pr900131e.
• [3] Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA.Future Oncol. 2018 Oct;14(25):2627-2642. doi: 10.2217/fon-2018-0267. Epub 2018 Jun 18.
• [4] Burden of Clostridium (Clostridioides) difficile infection during inpatient stays in the USA between 2012 and 2016.J Hosp Infect. 2019 Jun;102(2):135-140. doi: 10.1016/j.jhin.2019.01.020. Epub 2019 Jan 25.
• [5] Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency. Gastroenterology. 2014 Sep;147(3):595-598.e5. doi: 10.1053/j.gastro.2014.06.009. Epub 2014 Jun 15.
• [6] Update on genetic predisposition to colorectal cancer and polyposis.Mol Aspects Med. 2019 Oct;69:10-26. doi: 10.1016/j.mam.2019.03.001. Epub 2019 Mar 18.
• [7] 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.
• [8] Interplay between human nucleolar GNL1 and RPS20 is critical to modulate cell proliferation.Sci Rep. 2018 Jul 30;8(1):11421. doi: 10.1038/s41598-018-29802-y.
• [9] 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.
• [10] Expansion of germline RPS20 mutation phenotype to include Diamond-Blackfan anemia. Hum Mutat. 2020 Nov;41(11):1918-1930. doi: 10.1002/humu.24092. Epub 2020 Aug 30.
• [11] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [12] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [13] Validation of Recently Proposed Colorectal Cancer Susceptibility Gene Variants in an Analysis of Families and Patients-a Systematic Review.Gastroenterology. 2017 Jan;152(1):75-77.e4. doi: 10.1053/j.gastro.2016.09.041. Epub 2016 Oct 3.
• [14] Transancestral mapping and genetic load in systemic lupus erythematosus.Nat Commun. 2017 Jul 17;8:16021. doi: 10.1038/ncomms16021.
• [15] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [16] 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.
• [17] 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.
• [18] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [24] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [25] La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA Translation Downstream of mTOR Complex 1 (mTORC1). J Biol Chem. 2015 Jun 26;290(26):15996-6020. doi: 10.1074/jbc.M114.621730. Epub 2015 May 4.