Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB6SDZ1)

• DOT Name: Large ribosomal subunit protein eL37 (RPL37)
• Synonyms: 60S ribosomal protein L37; G1.16
• Gene Name: RPL37
• Related Disease:
  Colon cancer
  Colon carcinoma
  Schizophrenia
  Thyroiditis
  Neoplasm
• UniProt ID: RL37_HUMAN
• PDB ID: 4UG0 ; 4V6X ; 5AJ0 ; 5LKS ; 5T2C ; 6IP5 ; 6IP6 ; 6IP8 ; 6LQM ; 6LSR ; 6LSS ; 6LU8 ; 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 ; 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: PF01907
• Sequence:
  MTKGTSSFGKRRNKTHTLCRRCGSKAYHLQKSTCGKCGYPAKRKRKYNWSAKAKRRNTTG
  TGRMRHLKIVYRRFRHGFREGTTPKPKRAAVAASSSS
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[2]
Thyroiditis	DISTCV24	Strong	Genetic Variation	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

11 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 Large ribosomal subunit protein eL37 (RPL37).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Large ribosomal subunit protein eL37 (RPL37).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Large ribosomal subunit protein eL37 (RPL37).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Large ribosomal subunit protein eL37 (RPL37).	[8]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Large ribosomal subunit protein eL37 (RPL37).	[9]
Aluminium	DM6ECN9	Approved	Aluminium decreases the expression of Large ribosomal subunit protein eL37 (RPL37).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Large ribosomal subunit protein eL37 (RPL37).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Large ribosomal subunit protein eL37 (RPL37).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Large ribosomal subunit protein eL37 (RPL37).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Large ribosomal subunit protein eL37 (RPL37).	[16]
Manganese	DMKT129	Investigative	Manganese decreases the expression of Large ribosomal subunit protein eL37 (RPL37).	[10]

2 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 Large ribosomal subunit protein eL37 (RPL37).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Large ribosomal subunit protein eL37 (RPL37).	[15]

References

• [1] Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer.Metabolites. 2018 Jan 11;8(1):5. doi: 10.3390/metabo8010005.
• [2] Common variants on 8p12 and 1q24.2 confer risk of schizophrenia.Nat Genet. 2011 Oct 30;43(12):1224-7. doi: 10.1038/ng.980.
• [3] Coexistent thyroiditis is associated with lower tumour stage in thyroid carcinoma.Eur J Clin Invest. 1998 Oct;28(10):838-44. doi: 10.1046/j.1365-2362.1998.00363.x.
• [4] Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors.Am J Pathol. 2001 Jun;158(6):1955-9. doi: 10.1016/S0002-9440(10)64665-2.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] 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.
• [8] Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
• [9] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [10] Role of microRNA-4516 involved autophagy associated with exposure to fine particulate matter. Oncotarget. 2016 Jul 19;7(29):45385-45397. doi: 10.18632/oncotarget.9978.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] 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.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [16] 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.