Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAV1MJQ)

• DOT Name: Ribosomal protein eL39-like 2 (RPL39L)
• Synonyms: 60S ribosomal protein L39-2; 60S ribosomal protein L39-like; Large ribosomal subunit protein eL39-like
• Gene Name: RPL39L
• Related Disease:
  Hepatocellular carcinoma
  Neoplasm
  Ovarian cancer
• UniProt ID: RL39L_HUMAN
• Pfam ID: PF00832
• Sequence: MSSHKTFTIKRFLAKKQKQNRPIPQWIQMKPGSKIRYNSKRRHWRRTKLGL
• Function: Male germ cell-specific component of the ribosome, which is required for the formation of sperm and male fertility. Replaces the RPL39 paralog in the ribosome of male germ cells. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The male germ cell-specific ribosome displays a ribosomal polypeptide exit tunnel of distinct size and charge states compared with the classical ribosome. It is responsible for regulating the biosynthesis and folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm.
• Tissue Specificity: Testis specific.
• 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

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ribosomal protein eL39-like 2 (RPL39L).	[7]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[8]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Ribosomal protein eL39-like 2 (RPL39L).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ribosomal protein eL39-like 2 (RPL39L).	[14]

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 Ribosomal protein eL39-like 2 (RPL39L).	[10]

References

• [1] RPL39L is an example of a recently evolved ribosomal protein paralog that shows highly specific tissue expression patterns and is upregulated in ESCs and HCC tumors.RNA Biol. 2014;11(1):33-41. doi: 10.4161/rna.27427. Epub 2013 Dec 20.
• [2] Spermatogenesis associated retrogenes are expressed in the human ovary and ovarian cancers.PLoS One. 2009;4(3):e5064. doi: 10.1371/journal.pone.0005064. Epub 2009 Mar 31.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [9] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.