Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKFY73U)

• DOT Name: Small ribosomal subunit protein bS6m (MRPS6)
• Synonyms: 28S ribosomal protein S6, mitochondrial; MRP-S6; S6mt
• Gene Name: MRPS6
• Related Disease:
  Coronary atherosclerosis
  Coronary heart disease
  Myocardial infarction
• UniProt ID: RT06_HUMAN
• PDB ID: 3J9M ; 6NU2 ; 6NU3 ; 6RW4 ; 6RW5 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5I ; 7A5K ; 7L08 ; 7OG4 ; 7P2E ; 7PNX ; 7PNY ; 7PNZ ; 7PO0 ; 7PO1 ; 7PO2 ; 7PO3 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8CSP ; 8CSQ ; 8CSR ; 8CSS ; 8CST ; 8CSU ; 8OIR ; 8OIS
• Pfam ID: PF01250
• Sequence:
  MPRYELALILKAMQRPETAATLKRTIEALMDRGAIVRDLENLGERALPYRISAHSQQHNR
  GGYFLVDFYAPTAAVESMVEHLSRDIDVIRGNIVKHPLTQELKECEGIVPVPLAEKLYST
  KKRKK
• KEGG Pathway: Ribosome (hsa03010)
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Coronary atherosclerosis	DISKNDYU	Definitive	Biomarker	[1]
Coronary heart disease	DIS5OIP1	Definitive	Biomarker	[1]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Small ribosomal subunit protein bS6m (MRPS6).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Small ribosomal subunit protein bS6m (MRPS6).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Small ribosomal subunit protein bS6m (MRPS6).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[14]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[20]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Small ribosomal subunit protein bS6m (MRPS6).	[21]

References

• [1] Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.Nat Genet. 2011 Mar 6;43(4):333-8. doi: 10.1038/ng.784.
• [2] The rs9982601 polymorphism of the region between the SLC5A3/MRPS6 and KCNE2 genes associated with a prevalence of myocardial infarction and subsequent long-term mortality.Pol Arch Med Wewn. 2015;125(4):240-8. doi: 10.20452/pamw.2780. Epub 2015 Feb 20.
• [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] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [15] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] 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.
• [19] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [20] 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.
• [21] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.