Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNWGF5C)

• DOT Name: Ribosomal protein eL22-like (RPL22L1)
• Synonyms: 60S ribosomal protein L22-like 1; Large ribosomal subunit protein eL22-like 1
• Gene Name: RPL22L1
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Epithelial ovarian cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: RL22L_HUMAN
• Pfam ID: PF01776
• Sequence:
  MAPQKDRKPKRSTWRFNLDLTHPVEDGIFDSGNFEQFLREKVKVNGKTGNLGNVVHIERF
  KNKITVVSEKQFSKRYLKYLTKKYLKKNNLRDWLRVVASDKETYELRYFQISQDEDESES
  ED
• 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

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ribosomal protein eL22-like (RPL22L1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ribosomal protein eL22-like (RPL22L1).	[9]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Ribosomal protein eL22-like (RPL22L1).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ribosomal protein eL22-like (RPL22L1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ribosomal protein eL22-like (RPL22L1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ribosomal protein eL22-like (RPL22L1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Ribosomal protein eL22-like (RPL22L1).	[17]

References

• [1] Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition.PLoS One. 2015 Nov 30;10(11):e0143659. doi: 10.1371/journal.pone.0143659. eCollection 2015.
• [2] RPL22L1 induction in colorectal cancer is associated with poor prognosis and 5-FU resistance.PLoS One. 2019 Oct 3;14(10):e0222392. doi: 10.1371/journal.pone.0222392. eCollection 2019.
• [3] Identification of candidate diagnostic and prognostic biomarkers for human prostate cancer: RPL22L1 and RPS21.Med Oncol. 2019 May 14;36(6):56. doi: 10.1007/s12032-019-1283-z.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] 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.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [11] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] 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.
• [14] 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.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.