Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN9VRD2)

• DOT Name: Large ribosomal subunit protein mL39 (MRPL39)
• Synonyms: 39S ribosomal protein L39, mitochondrial; L39mt; MRP-L39; 39S ribosomal protein L5, mitochondrial; L5mt; MRP-L5
• Gene Name: MRPL39
• Related Disease:
  Mitochondrial disease
  Gastric cancer
  Neoplasm
  Stomach cancer
• UniProt ID: RM39_HUMAN
• PDB ID: 3J7Y ; 3J9M ; 5OOL ; 5OOM ; 6I9R ; 6NU2 ; 6NU3 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5H ; 7A5I ; 7A5J ; 7A5K ; 7L08 ; 7L20 ; 7O9K ; 7O9M ; 7ODR ; 7ODS ; 7ODT ; 7OF0 ; 7OF2 ; 7OF3 ; 7OF4 ; 7OF5 ; 7OF6 ; 7OF7 ; 7OG4 ; 7OI6 ; 7OI7 ; 7OI8 ; 7OI9 ; 7OIA ; 7OIB ; 7OIC ; 7OID ; 7OIE ; 7PD3 ; 7PO4 ; 7QH6 ; 7QH7 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8OIR ; 8OIT
• Sequence:
  MEALAMGSRALRLWLVAPGGGIKWRFIATSSASQLSPTELTEMRNDLFNKEKARQLSLTP
  RTEKIEVKHVGKTDPGTVFVMNKNISTPYSCAMHLSEWYCRKSILALVDGQPWDMYKPLT
  KSCEIKFLTFKDCDPGEVNKAYWRSCAMMMGCVIERAFKDEYMVNLVRAPEVPVISGAFC
  YDVVLDSKLDEWMPTKENLRSFTKDAHALIYKDLPFETLEVEAKVALEIFQHSKYKVDFI
  EEKASQNPERIVKLHRIGDFIDVSEGPLIPRTSICFQYEVSAVHNLQPTQPSLIRRFQGV
  SLPVHLRAHFTIWDKLLERSRKMVTEDQSKATEECTST
• Tissue Specificity: Isoform 1 is ubiquitously expressed. Isoform 2 is heart-specific.
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Moderate	Autosomal recessive	[1]
Gastric cancer	DISXGOUK	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Stomach cancer	DISKIJSX	Limited	Biomarker	[2]

9 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 mL39 (MRPL39).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Large ribosomal subunit protein mL39 (MRPL39).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Large ribosomal subunit protein mL39 (MRPL39).	[12]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Long Noncoding RNA MRPL39 Inhibits Gastric Cancer Proliferation and Progression by Directly Targeting miR-130.Genet Test Mol Biomarkers. 2018 Nov;22(11):656-663. doi: 10.1089/gtmb.2018.0151.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.