Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXI1YLM)

• DOT Name: Large ribosomal subunit protein uL14 (RPL23)
• Synonyms: 60S ribosomal protein L17; 60S ribosomal protein L23
• Gene Name: RPL23
• Related Disease:
  Advanced cancer
  Autoimmune disease
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Childhood myelodysplastic syndrome
  Colorectal carcinoma
  Diamond-Blackfan anemia
  Focal segmental glomerulosclerosis
  Gastric cancer
  Macular corneal dystrophy
  Neoplasm
  Stomach cancer
  Gastric neoplasm
  Myelodysplastic syndrome
  Venous thromboembolism
• UniProt ID: RL23_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7F5S ; 7OW7 ; 7XNX ; 7XNY ; 8A3D ; 8FKP ; 8FKQ ; 8FKR ; 8FKS ; 8FKT ; 8FKU ; 8FKV ; 8FKW ; 8FKX ; 8FKY ; 8FKZ ; 8FL0 ; 8FL2 ; 8FL3 ; 8FL4 ; 8FL7 ; 8FL9 ; 8FLA ; 8FLB ; 8FLC ; 8FLD ; 8FLE ; 8FLF ; 8G5Y ; 8G5Z ; 8G60 ; 8G61 ; 8G6J ; 8GLP ; 8IDT ; 8IDY ; 8IE3 ; 8INE ; 8INF ; 8INK ; 8IPD ; 8IPX ; 8IPY ; 8IR1 ; 8IR3 ; 8JDJ ; 8JDK ; 8JDL ; 8JDM
• Pfam ID: PF00238
• Sequence:
  MSKRGRGGSSGAKFRISLGLPVGAVINCADNTGAKNLYIISVKGIKGRLNRLPAAGVGDM
  VMATVKKGKPELRKKVHPAVVIRQRKSYRRKDGVFLYFEDNAGVIVNNKGEMKGSAITGP
  VAKECADLWPRIASNAGSIA
• Function: Component of the large 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)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  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)
  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

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Autoimmune disease	DISORMTM	Strong	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Diamond-Blackfan anemia	DISI2SNW	Strong	Biomarker	[7]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Altered Expression	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Macular corneal dystrophy	DISOLD0H	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Gastric neoplasm	DISOKN4Y	Disputed	Biomarker	[11]
Myelodysplastic syndrome	DISYHNUI	Limited	Altered Expression	[5]
Venous thromboembolism	DISUR7CR	Limited	Biomarker	[12]

1 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 Large ribosomal subunit protein uL14 (RPL23).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Large ribosomal subunit protein uL14 (RPL23).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large ribosomal subunit protein uL14 (RPL23).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Large ribosomal subunit protein uL14 (RPL23).	[16]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Large ribosomal subunit protein uL14 (RPL23).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein uL14 (RPL23).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Large ribosomal subunit protein uL14 (RPL23).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Large ribosomal subunit protein uL14 (RPL23).	[20]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Large ribosomal subunit protein uL14 (RPL23).	[21]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Large ribosomal subunit protein uL14 (RPL23).	[22]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Large ribosomal subunit protein uL14 (RPL23).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Large ribosomal subunit protein uL14 (RPL23).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein uL14 (RPL23).	[24]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Large ribosomal subunit protein uL14 (RPL23).	[25]

References

• [1] Inhibition of the p53-MDM2 interaction by adenovirus delivery of ribosomal protein L23 stabilizes p53 and induces cell cycle arrest and apoptosis in gastric cancer.J Gene Med. 2010 Feb;12(2):147-56. doi: 10.1002/jgm.1424.
• [2] The evolutionarily conserved ribosomal protein L23 and the cationic urease beta-subunit of Yersinia enterocolitica O:3 belong to the immunodominant antigens in Yersinia-triggered reactive arthritis: implications for autoimmunity.Mol Med. 1994 Nov;1(1):44-55.
• [3] A super-SILAC based proteomics analysis of diffuse large B-cell lymphoma-NOS patient samples to identify new proteins that discriminate GCB and non-GCB lymphomas.PLoS One. 2019 Oct 11;14(10):e0223260. doi: 10.1371/journal.pone.0223260. eCollection 2019.
• [4] Co-expression network analysis of gene expression profiles of HER2(+) breast cancer-associated brain metastasis.Oncol Lett. 2018 Dec;16(6):7008-7019. doi: 10.3892/ol.2018.9562. Epub 2018 Oct 10.
• [5] Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome.Sci Rep. 2017 May 24;7(1):2323. doi: 10.1038/s41598-017-02403-x.
• [6] Growth inhibitory effect of adenovirus-mediated tissue-targeted expression of ribosomal protein L23 on human colorectal carcinoma cells.Oncol Rep. 2015 Aug;34(2):763-70. doi: 10.3892/or.2015.4026. Epub 2015 Jun 4.
• [7] Germline Genetic Predisposition to Hematologic Malignancy.J Clin Oncol. 2017 Mar 20;35(9):1018-1028. doi: 10.1200/JCO.2016.70.8644. Epub 2017 Feb 13.
• [8] Comparative differential proteomic analysis of minimal change disease and focal segmental glomerulosclerosis.BMC Nephrol. 2017 Feb 3;18(1):49. doi: 10.1186/s12882-017-0452-6.
• [9] Co-transduction of ribosomal protein L23 enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in human gastric cancer.Oncol Rep. 2013 Oct;30(4):1989-95. doi: 10.3892/or.2013.2663. Epub 2013 Aug 7.
• [10] GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system.J Cell Sci. 2018 Aug 3;131(15):jcs213009. doi: 10.1242/jcs.213009.
• [11] Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer cells by suppressing drug-induced apoptosis.Exp Cell Res. 2004 Jun 10;296(2):337-46. doi: 10.1016/j.yexcr.2004.02.009.
• [12] Identification of biomarkers of venous thromboembolism by bioinformatics analyses.Medicine (Baltimore). 2018 Apr;97(14):e0152. doi: 10.1097/MD.0000000000010152.
• [13] 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.
• [14] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [15] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [16] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [17] 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.
• [18] 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.
• [19] [Construction of subtracted cDNA library in human Jurkat T cell line induced by arsenic trioxide in vitro]. Zhonghua Yu Fang Yi Xue Za Zhi. 2003 Nov;37(6):403-7.
• [20] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [21] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [22] 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.
• [23] 5-Fluorouracil: identification of novel downstream mediators of tumour response. Anticancer Res. 2004 Mar-Apr;24(2A):417-23.
• [24] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [25] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.