Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE3VSAH)

• DOT Name: Small ribosomal subunit protein eS10 (RPS10)
• Synonyms: 40S ribosomal protein S10
• Gene Name: RPS10
• Related Disease:
  Acne vulgaris
  Diamond-Blackfan anemia
  Advanced cancer
  Benign prostatic hyperplasia
  Diamond-Blackfan anemia 6
  Diamond-Blackfan anemia 9
  Hepatocellular carcinoma
  Liver failure
  Schizophrenia
• UniProt ID: RS10_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 ; 7QVP ; 7R4X ; 7TQL ; 7XNX ; 7XNY ; 8G5Y ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF03501
• Sequence:
  MLMPKKNRIAIYELLFKEGVMVAKKDVHMPKHPELADKNVPNLHVMKAMQSLKSRGYVKE
  QFAWRHFYWYLTNEGIQYLRDYLHLPPEIVPATLRRSRPETGRPRPKGLEGERPARLTRG
  EADRDTYRRSAVPPGADKKAEAGAGSATEFQFRGGFGRGRGQPPQ
• Function: Component of the 40S 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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acne vulgaris	DISKW8PI	Definitive	Biomarker	[1]
Diamond-Blackfan anemia	DISI2SNW	Definitive	Autosomal dominant	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[4]
Diamond-Blackfan anemia 6	DIS4FKKF	Strong	Biomarker	[5]
Diamond-Blackfan anemia 9	DIS84ATX	Strong	Autosomal dominant	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Liver failure	DISLGEL6	Strong	Biomarker	[8]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[9]

8 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 eS10 (RPS10).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Small ribosomal subunit protein eS10 (RPS10).	[12]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Small ribosomal subunit protein eS10 (RPS10).	[13]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Small ribosomal subunit protein eS10 (RPS10).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Small ribosomal subunit protein eS10 (RPS10).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Small ribosomal subunit protein eS10 (RPS10).	[17]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Small ribosomal subunit protein eS10 (RPS10).	[18]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Small ribosomal subunit protein eS10 (RPS10).	[19]

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 Small ribosomal subunit protein eS10 (RPS10).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Small ribosomal subunit protein eS10 (RPS10).	[15]

References

• [1] Propionibacterium acnes is developing gradual increase in resistance to oral tetracyclines.J Med Microbiol. 2017 Jan;66(1):8-12. doi: 10.1099/jmm.0.000392.
• [2] 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.
• [3] Morin suppresses cachexia-induced muscle wasting by binding to ribosomal protein S10 in carcinoma cells.Biochem Biophys Res Commun. 2018 Dec 2;506(4):773-779. doi: 10.1016/j.bbrc.2018.10.184. Epub 2018 Oct 31.
• [4] The prostate cancer immunome: In silico functional analysis of antigenic proteins from microarray profiling with IgG.Proteomics. 2016 Apr;16(8):1204-14. doi: 10.1002/pmic.201500378. Epub 2016 Apr 4.
• [5] A high-throughput approach for measuring temporal changes in the interactome.Nat Methods. 2012 Sep;9(9):907-9. doi: 10.1038/nmeth.2131. Epub 2012 Aug 5.
• [6] 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.
• [7] Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags.Int J Oncol. 2006 Aug;29(2):315-27.
• [8] Two-dimensional electrophoretic analysis of ribosomal proteins from chronically injured liver.J Clin Chem Clin Biochem. 1979 Aug;17(8):541-5. doi: 10.1515/cclm.1979.17.8.541.
• [9] Alterations in oligodendrocyte proteins, calcium homeostasis and new potential markers in schizophrenia anterior temporal lobe are revealed by shotgun proteome analysis.J Neural Transm (Vienna). 2009 Mar;116(3):275-89. doi: 10.1007/s00702-008-0156-y. Epub 2008 Nov 26.
• [10] 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.
• [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] Hydrogen peroxide induces adaptive response and differential gene expression in human embryo lung fibroblast cells. Environ Toxicol. 2014 Apr;29(4):478-85. doi: 10.1002/tox.21775. Epub 2012 Apr 7.
• [13] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [14] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [17] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [18] 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.
• [19] 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.