Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCC1872)

• DOT Name: Small ribosomal subunit protein uS14 (RPS29)
• Synonyms: 40S ribosomal protein S29
• Gene Name: RPS29
• Related Disease:
  Diamond-Blackfan anemia 6
  Colon carcinoma
  Diamond-Blackfan anemia 13
  Head-neck squamous cell carcinoma
  Lung neoplasm
  Penile cancer
  Diamond-Blackfan anemia
• UniProt ID: RS29_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 ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8JDJ ; 8JDK ; 8JDL ; 8JDM ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF00253
• Sequence: MGHQQLYWSHPRKFGQGSRSCRVCSNRHGLIRKYGLNMCRQCFRQYAKDIGFIKLD
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diamond-Blackfan anemia 6	DIS4FKKF	Definitive	GermlineCausalMutation	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Diamond-Blackfan anemia 13	DISNEUZI	Strong	Autosomal dominant	[1]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[3]
Lung neoplasm	DISVARNB	Strong	Biomarker	[4]
Penile cancer	DISGVGNQ	Strong	Genetic Variation	[5]
Diamond-Blackfan anemia	DISI2SNW	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Small ribosomal subunit protein uS14 (RPS29).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Small ribosomal subunit protein uS14 (RPS29).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small ribosomal subunit protein uS14 (RPS29).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein uS14 (RPS29).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Small ribosomal subunit protein uS14 (RPS29).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Small ribosomal subunit protein uS14 (RPS29).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Small ribosomal subunit protein uS14 (RPS29).	[12]
Palbociclib	DMD7L94	Approved	Palbociclib increases the expression of Small ribosomal subunit protein uS14 (RPS29).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Small ribosomal subunit protein uS14 (RPS29).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Small ribosomal subunit protein uS14 (RPS29).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small ribosomal subunit protein uS14 (RPS29).	[17]

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 uS14 (RPS29).	[15]

References

• [1] Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families. Blood. 2014 Jul 3;124(1):24-32. doi: 10.1182/blood-2013-11-540278. Epub 2014 May 14.
• [2] The S29 ribosomal protein increases tumor suppressor activity of K rev-1 gene on v-K ras-transformed NIH3T3 cells.Biochim Biophys Acta. 1996 Aug 21;1313(1):41-6. doi: 10.1016/0167-4889(96)00052-3.
• [3] Reference gene selection for head and neck squamous cell carcinoma gene expression studies.BMC Mol Biol. 2009 Aug 3;10:78. doi: 10.1186/1471-2199-10-78.
• [4] Low content of protein S29 in ribosomes of human lung cancer cell line a549: detected by two-dimensional electrophoresis.Protein Pept Lett. 2003 Feb;10(1):91-7. doi: 10.2174/0929866033408273.
• [5] Systematic review and evidence synthesis of non-cervical human papillomavirus-related disease health system costs and quality of life estimates.Sex Transm Infect. 2019 Feb;95(1):28-35. doi: 10.1136/sextrans-2018-053606. Epub 2018 Sep 21.
• [6] Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact. 2010 Oct 6;188(1):214-9.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [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] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [11] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [12] 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.
• [13] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [14] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [15] 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.
• [16] 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.
• [17] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.