Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBRQ8MS)

• DOT Name: Small ribosomal subunit protein eS12 (RPS12)
• Synonyms: 40S ribosomal protein S12
• Gene Name: RPS12
• UniProt ID: RS12_HUMAN
• PDB ID: 4V6X ; 5A2Q ; 5AJ0 ; 5FLX ; 5LKS ; 5OA3 ; 5T2C ; 5VYC ; 6FEC ; 6G18 ; 6G51 ; 6G53 ; 6G5H ; 6G5I ; 6IP5 ; 6IP6 ; 6IP8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6XA1 ; 6Y0G ; 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 ; 7MQ8 ; 7MQ9 ; 7MQA ; 7QP6 ; 7QP7 ; 7R4X ; 7TQL ; 7WTT ; 7WTU ; 7WTV ; 7WTW ; 7WTX ; 7WTZ ; 7WU0 ; 7XNX ; 7XNY ; 8G5Y ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8PPK ; 8PPL ; 8T4S
• Pfam ID: PF01248
• Sequence:
  MAEEGIAAGGVMDVNTALQEVLKTALIHDGLARGIREAAKALDKRQAHLCVLASNCDEPM
  YVKLVEALCAEHQINLIKVDDNKKLGEWVGLCKIDREGKPRKVVGCSCVVVKDYGKESQA
  KDVIEEYFKCKK
• Function: 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. Subunit of the 40S ribosomal complex.
• 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

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	Small ribosomal subunit protein eS12 (RPS12) decreases the response to substance of Artesunate.	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small ribosomal subunit protein eS12 (RPS12).	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small ribosomal subunit protein eS12 (RPS12).	[2]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Small ribosomal subunit protein eS12 (RPS12).	[3]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Small ribosomal subunit protein eS12 (RPS12).	[5]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Small ribosomal subunit protein eS12 (RPS12).	[6]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Small ribosomal subunit protein eS12 (RPS12).	[7]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Investigative	(E)-4-(3,5-dimethoxystyryl)phenol decreases the expression of Small ribosomal subunit protein eS12 (RPS12).	[8]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the expression of Small ribosomal subunit protein eS12 (RPS12).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Small ribosomal subunit protein eS12 (RPS12).	[4]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] 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.
• [3] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [4] 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.
• [5] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [6] Proteomic analysis of proteins associated with cellular senescence by calorie restriction in mesenchymal stem cells. In Vitro Cell Dev Biol Anim. 2012 Mar;48(3):186-95.
• [7] Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol. 2009 Jun;22(6):1077-85.
• [8] Proteomic identification of pterostilbene-mediated anticancer activities in HepG2 cells. Chem Res Toxicol. 2014 Jul 21;27(7):1243-52. doi: 10.1021/tx5001392. Epub 2014 Jul 1.
• [9] Potential role of nucleoside diphosphate kinase in myricetin-induced selective apoptosis in colon cancer HCT-15?cells. Food Chem Toxicol. 2018 Jun;116(Pt B):315-322. doi: 10.1016/j.fct.2018.04.053. Epub 2018 Apr 24.
• [10] Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.