Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFNRC27)

• DOT Name: Large ribosomal subunit protein uL24 (RPL26)
• Synonyms: 60S ribosomal protein L26
• Gene Name: RPL26
• Related Disease:
  Cytomegalovirus infection
  Diamond-Blackfan anemia 11
  Diamond-Blackfan anemia 6
  Herpes simplex infection
  Pancreatic cancer
  Diamond-Blackfan anemia
• UniProt ID: RL26_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 6OLE ; 6OLF ; 6OLG ; 6OLI ; 6OLZ ; 6OM0 ; 6OM7 ; 6QZP ; 6SXO ; 6W6L ; 6XA1 ; 6Y0G ; 6Y2L ; 6Y57 ; 6Y6X ; 6Z6L ; 6Z6M ; 6Z6N ; 6ZM7 ; 6ZME ; 6ZMI ; 6ZMO ; 7BHP ; 7F5S ; 7OW7 ; 7XNX ; 7XNY ; 8A3D ; 8FKP ; 8FKQ ; 8FKR ; 8FKS ; 8FKT ; 8FKU ; 8FKV ; 8FKW ; 8FKX ; 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: PF00467 ; PF16906
• Sequence:
  MKFNPFVTSDRSKNRKRHFNAPSHIRRKIMSSPLSKELRQKYNVRSMPIRKDDEVQVVRG
  HYKGQQIGKVVQVYRKKYVIYIERVQREKANGTTVHVGIHPSKVVITRLKLDKDRKKILE
  RKAKSRQVGKEKGKYKEETIEKMQE
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[1]
Diamond-Blackfan anemia 11	DISQ0PDQ	Strong	Autosomal dominant	[2]
Diamond-Blackfan anemia 6	DIS4FKKF	Strong	GermlineCausalMutation	[2]
Herpes simplex infection	DISL1SAV	Strong	Altered Expression	[3]
Pancreatic cancer	DISJC981	Strong	Biomarker	[4]
Diamond-Blackfan anemia	DISI2SNW	Supportive	Autosomal dominant	[5]

10 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 uL24 (RPL26).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein uL24 (RPL26).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Large ribosomal subunit protein uL24 (RPL26).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Large ribosomal subunit protein uL24 (RPL26).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Large ribosomal subunit protein uL24 (RPL26).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Large ribosomal subunit protein uL24 (RPL26).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein uL24 (RPL26).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Large ribosomal subunit protein uL24 (RPL26).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large ribosomal subunit protein uL24 (RPL26).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Large ribosomal subunit protein uL24 (RPL26).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Large ribosomal subunit protein uL24 (RPL26).	[14]

References

• [1] Distinct domains within the human cytomegalovirus U(L)26 protein are important for wildtype viral replication and virion stability.PLoS One. 2014 Feb 5;9(2):e88101. doi: 10.1371/journal.pone.0088101. eCollection 2014.
• [2] Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia. Hum Mutat. 2012 Jul;33(7):1037-44. doi: 10.1002/humu.22081. Epub 2012 Apr 16.
• [3] DNA sequence-specific ligands. XVII. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric bisbenzimidazoles DBA(n).Bioorg Med Chem. 2018 May 15;26(9):2302-2309. doi: 10.1016/j.bmc.2018.03.018. Epub 2018 Mar 12.
• [4] Silencing expression of ribosomal protein L26 and L29 by RNA interfering inhibits proliferation of human pancreatic cancer PANC-1 cells.Mol Cell Biochem. 2012 Nov;370(1-2):127-39. doi: 10.1007/s11010-012-1404-x. Epub 2012 Aug 7.
• [5] Diamond-Blackfan Anemia. 2009 Jun 25 [updated 2023 Mar 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] 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.
• [13] 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.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.