Details of Drug Off-Target (DOT)

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

• DOT Name: Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1)
• Synonyms: Putative heme chaperone
• Gene Name: RSAD1
• UniProt ID: RSAD1_HUMAN
• Pfam ID: PF06969 ; PF04055
• Sequence:
  MALPGARARGWAAAARAAQRRRRVENAGGSPSPEPAGRRAALYVHWPYCEKRCSYCNFNK
  YIPRRLEEAAMQKCLVTEAQTLLRLSGVQRVESVFFGGGTPSLASPHTVAAVLEAVAQAA
  HLPADLEVTLEANPTSAPGSRLAEFGAAGVNRLSIGLQSLDDTELRLLGRTHSACDALRT
  LAEARRLFPGRVSVDLMLGLPAQQVGPWLGQLQELLHHCDDHLSLYQLSLERGTALFAQV
  QRGALPAPDPELAAEMYQRGRAVLREAGFHQYEVSNFARNGALSTHNWTYWQCGQYLGVG
  PGAHGRFMPQGAGGHTREARIQTLEPDNWMKEVMLFGHGTRKRVPLGRLELLEEVLALGL
  RTDVGITHQHWQQFEPQLTLWDVFGANKEVQELLERGLLQLDHRGLRCSWEGLAVLDSLL
  LTLLPQLQEAWQQRTPSPVPGG
• Function: May be a heme chaperone, appears to bind heme. Homologous bacterial proteins do not have oxygen-independent coproporphyrinogen-III oxidase activity (Probable). Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[13]

1 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 affects the methylation of Radical S-adenosyl methionine domain-containing protein 1, mitochondrial (RSAD1).	[11]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 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.
• [8] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] 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.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.