Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0U9VMQ)

• DOT Name: Large ribosomal subunit protein eL34 (RPL34)
• Synonyms: 60S ribosomal protein L34
• Gene Name: RPL34
• Related Disease:
  Carcinoma of esophagus
  Esophageal cancer
  Neoplasm of esophagus
  Advanced cancer
  Depression
  Gastric cancer
  Glioma
  Major depressive disorder
  Neoplasm
  Non-small-cell lung cancer
  Pancreatic cancer
  Stomach cancer
  Synovial sarcoma
  Retinoblastoma
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: RL34_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6MTD ; 6MTE ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6W6L ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7BHP ; 7F5S ; 7OW7 ; 7XNX ; 7XNY ; 8A3D ; 8FKY ; 8FKZ ; 8FL2 ; 8FL3 ; 8FL4 ; 8FL6 ; 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: PF01199
• Sequence:
  MVQRLTYRRRLSYNTASNKTRLSRTPGNRIVYLYTKKVGKAPKSACGVCPGRLRGVRAVR
  PKVLMRLSKTKKHVSRAYGGSMCAKCVRDRIKRAFLIEEQKIVVKVLKAQAQSQKAK
• 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
Carcinoma of esophagus	DISS6G4D	Definitive	Biomarker	[1]
Esophageal cancer	DISGB2VN	Definitive	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Major depressive disorder	DIS4CL3X	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[5]
Pancreatic cancer	DISJC981	Strong	Biomarker	[6]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[3]
Synovial sarcoma	DISEZJS7	Strong	Genetic Variation	[7]
Retinoblastoma	DISVPNPB	moderate	Biomarker	[8]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[9]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[9]

12 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 Large ribosomal subunit protein eL34 (RPL34).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Large ribosomal subunit protein eL34 (RPL34).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein eL34 (RPL34).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Large ribosomal subunit protein eL34 (RPL34).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Large ribosomal subunit protein eL34 (RPL34).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein eL34 (RPL34).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Large ribosomal subunit protein eL34 (RPL34).	[16]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Large ribosomal subunit protein eL34 (RPL34).	[17]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Large ribosomal subunit protein eL34 (RPL34).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein eL34 (RPL34).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein eL34 (RPL34).	[20]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Large ribosomal subunit protein eL34 (RPL34).	[21]

References

• [1] Silencing of Ribosomal Protein L34 (RPL34) Inhibits the Proliferation and Invasion of Esophageal Cancer Cells.Oncol Res. 2017 Aug 7;25(7):1061-1068. doi: 10.3727/096504016X14830466773541. Epub 2017 Jan 20.
• [2] Integrated profiling of phenotype and blood transcriptome for stress vulnerability and depression.J Psychiatr Res. 2018 Sep;104:202-210. doi: 10.1016/j.jpsychires.2018.08.010. Epub 2018 Aug 6.
• [3] RNAi-mediated RPL34 knockdown suppresses the growth of human gastric cancer cells.Oncol Rep. 2015 Nov;34(5):2267-72. doi: 10.3892/or.2015.4219. Epub 2015 Aug 21.
• [4] Knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK/STAT3 signaling pathway.J Cell Biochem. 2019 Mar;120(3):3259-3267. doi: 10.1002/jcb.27592. Epub 2018 Sep 14.
• [5] Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells.Gene. 2016 Jan 15;576(1 Pt 3):421-8. doi: 10.1016/j.gene.2015.10.053. Epub 2015 Oct 23.
• [6] Ribosomal protein L34 promotes the proliferation, invasion and metastasis of pancreatic cancer cells.Oncotarget. 2016 Dec 20;7(51):85259-85272. doi: 10.18632/oncotarget.13269.
• [7] The synovial sarcoma associated protein SYT interacts with the acute leukemia associated protein AF10.Oncogene. 2001 May 31;20(25):3281-9. doi: 10.1038/sj.onc.1204419.
• [8] Deficiency of a novel retinoblastoma binding protein 2-homolog is a consistent feature of sporadic human melanoma skin cancer.Lab Invest. 1999 Dec;79(12):1615-27.
• [9] Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control.Sci Rep. 2016 Nov 24;6:37690. doi: 10.1038/srep37690.
• [10] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [11] 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.
• [12] Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact. 2010 Oct 6;188(1):214-9.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [18] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [19] 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.
• [20] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [21] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.