Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBS15SD)

• DOT Name: Mitochondrial peptide methionine sulfoxide reductase (MSRA)
• Synonyms: EC 1.8.4.11; Peptide-methionine (S)-S-oxide reductase; Peptide Met(O) reductase; Protein-methionine-S-oxide reductase; PMSR
• Gene Name: MSRA
• UniProt ID: MSRA_HUMAN
• EC Number: 1.8.4.11
• Pfam ID: PF01625
• Sequence:
  MLSATRRACQLLLLHSLFPVPRMGNSASNIVSPQEALPGRKEQTPVAAKHHVNGNRTVEP
  FPEGTQMAVFGMGCFWGAERKFWVLKGVYSTQVGFAGGYTSNPTYKEVCSEKTGHAEVVR
  VVYQPEHMSFEELLKVFWENHDPTQGMRQGNDHGTQYRSAIYPTSAKQMEAALSSKENYQ
  KVLSEHGFGPITTDIREGQTFYYAEDYHQQYLSKNPNGYCGLGGTGVSCPVGIKK
• Function: Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.
• Tissue Specificity: Ubiquitous. Highest expression in adult kidney and cerebellum, followed by liver, heart ventricles, bone marrow and hippocampus.
• Reactome Pathway: Protein repair (R-HSA-5676934)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bevacizumab	DMSD1UN	Approved	Mitochondrial peptide methionine sulfoxide reductase (MSRA) increases the Hypertension ADR of Bevacizumab.	[13]

10 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 Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Mitochondrial peptide methionine sulfoxide reductase (MSRA).	[12]

References

• [1] 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.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Resveratrol preconditioning increases methionine sulfoxide reductases A expression and enhances resistance of human neuroblastoma cells to neurotoxins. J Nutr Biochem. 2013 Jun;24(6):1070-7. doi: 10.1016/j.jnutbio.2012.08.005. Epub 2012 Sep 28.
• [10] 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.
• [11] 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.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100. Br J Cancer. 2014 Sep 9;111(6):1241-8. doi: 10.1038/bjc.2014.430. Epub 2014 Aug 12.