Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN5PNSP)

• DOT Name: Large ribosomal subunit protein mL49 (MRPL49)
• Synonyms: 39S ribosomal protein L49, mitochondrial; L49mt; MRP-L49; Neighbor of FAU; NOF; Protein NOF1
• Gene Name: MRPL49
• Related Disease:
  Melanoma
  Osteoarthritis
  Osteoporosis
• UniProt ID: RM49_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
• Pfam ID: PF05046
• Sequence:
  MAATMFRATLRGWRTGVQRGCGLRLLSQTQGPPDYPRFVESVDEYQFVERLLPATRIPDP
  PKHEHYPTPSGWQPPRDPPPNLPYFVRRSRMHNIPVYKDITHGNRQMTVIRKVEGDIWAL
  QKDVEDFLSPLLGKTPVTQVNEVTGTLRIKGYFDQELKAWLLEKGF
• Tissue Specificity: Ubiquitous.
• 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
Melanoma	DIS1RRCY	Strong	Biomarker	[1]
Osteoarthritis	DIS05URM	Strong	Biomarker	[2]
Osteoporosis	DISF2JE0	Strong	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Large ribosomal subunit protein mL49 (MRPL49) decreases the response to substance of Arsenic trioxide.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Large ribosomal subunit protein mL49 (MRPL49).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[12]
Phenol	DM1QSM3	Phase 2/3	Phenol decreases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Large ribosomal subunit protein mL49 (MRPL49).	[16]

References

• [1] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [2] Suppressors of cytokine signalling (SOCS) are reduced in osteoarthritis.Biochem Biophys Res Commun. 2011 Apr 1;407(1):54-9. doi: 10.1016/j.bbrc.2011.02.101. Epub 2011 Feb 23.
• [3] The impact of the new National Bone Health Alliance (NBHA) diagnostic criteria on the prevalence of osteoporosis in the United States: supplementary presentation.Osteoporos Int. 2017 Nov;28(11):3283-3284. doi: 10.1007/s00198-017-4207-9. Epub 2017 Sep 21.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [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] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] 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.
• [12] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [13] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.