Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIK25WI)

• DOT Name: Small ribosomal subunit protein eS7 (RPS7)
• Synonyms: 40S ribosomal protein S7
• Gene Name: RPS7
• Related Disease:
  Gastric cancer
  Stomach cancer
  Anemia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colorectal carcinoma
  Diamond-Blackfan anemia 1
  Diamond-Blackfan anemia 8
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Tuberculosis
  Diamond-Blackfan anemia
  Advanced cancer
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: RS7_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 ; 6YBD ; 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 ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF01251
• Sequence:
  MFSSSAKIVKPNGEKPDEFESGISQALLELEMNSDLKAQLRELNITAAKEIEVGGGRKAI
  IIFVPVPQLKSFQKIQVRLVRELEKKFSGKHVVFIAQRRILPKPTRKSRTKNKQKRPRSR
  TLTAVHDAILEDLVFPSEIVGKRIRVKLDGSRLIKVHLDKAQQNNVEHKVETFSGVYKKL
  TGKDVNFEFPEFQL
• Function: Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Required for rRNA maturation. 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)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)
  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

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Anemia	DISTVL0C	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Diamond-Blackfan anemia 1	DISP4NUV	Strong	Genetic Variation	[5]
Diamond-Blackfan anemia 8	DIS4EPFG	Strong	Autosomal dominant	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Altered Expression	[7]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[7]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[7]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[8]
Diamond-Blackfan anemia	DISI2SNW	Supportive	Autosomal dominant	[9]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[10]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Small ribosomal subunit protein eS7 (RPS7).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Small ribosomal subunit protein eS7 (RPS7).	[15]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Small ribosomal subunit protein eS7 (RPS7).	[16]

8 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 eS7 (RPS7).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein eS7 (RPS7).	[13]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Small ribosomal subunit protein eS7 (RPS7).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Small ribosomal subunit protein eS7 (RPS7).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Small ribosomal subunit protein eS7 (RPS7).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein eS7 (RPS7).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Small ribosomal subunit protein eS7 (RPS7).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Small ribosomal subunit protein eS7 (RPS7).	[20]

References

• [1] Aurora kinase B inhibitor barasertib (AZD1152) inhibits glucose metabolism in gastric cancer cells.Anticancer Drugs. 2019 Jan;30(1):19-26. doi: 10.1097/CAD.0000000000000684.
• [2] Mutation of the diamond-blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes.PLoS Genet. 2013;9(1):e1003094. doi: 10.1371/journal.pgen.1003094. Epub 2013 Jan 31.
• [3] An integrative approach to identify YB-1-interacting proteins required for cisplatin resistance in MCF7 and MDA-MB-231 breast cancer cells. Cancer Sci. 2011 Jul;102(7):1410-7. doi: 10.1111/j.1349-7006.2011.01948.x. Epub 2011 May 5.
• [4] RPS7 inhibits colorectal cancer growth via decreasing HIF-1-mediated glycolysis.Oncotarget. 2016 Feb 2;7(5):5800-14. doi: 10.18632/oncotarget.6807.
• [5] Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2010 Feb 12;86(2):222-8. doi: 10.1016/j.ajhg.2009.12.015. Epub 2010 Jan 28.
• [6] Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. Br J Haematol. 2013 Aug;162(4):530-6. doi: 10.1111/bjh.12397. Epub 2013 May 30.
• [7] RPS7 promotes cell migration through targeting epithelial-mesenchymal transition in prostate cancer.Urol Oncol. 2019 May;37(5):297.e1-297.e7. doi: 10.1016/j.urolonc.2019.01.011. Epub 2019 Feb 6.
• [8] Structural insights into the complex of trigger factor chaperone and ribosomal protein S7 from Mycobacterium tuberculosis.Biochem Biophys Res Commun. 2019 May 14;512(4):838-844. doi: 10.1016/j.bbrc.2019.03.166. Epub 2019 Mar 28.
• [9] Diamond-Blackfan Anemia. 2009 Jun 25 [updated 2023 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [10] Small ribosomal protein subunit S7 suppresses ovarian tumorigenesis through regulation of the PI3K/AKT and MAPK pathways.PLoS One. 2013 Nov 11;8(11):e79117. doi: 10.1371/journal.pone.0079117. eCollection 2013.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] 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.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
• [20] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.