Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG2GBBV)

• DOT Name: Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3)
• Synonyms: EC 5.4.99.-; RNA pseudouridylate synthase domain-containing protein 3
• Gene Name: RPUSD3
• UniProt ID: RUSD3_HUMAN
• EC Number: 5.4.99.-
• Pfam ID: PF00849
• Sequence:
  MRAVLAREMDGRRVLGRFWSGWRRGLGVRPVPEDAGFGTEARHQRQPRGSCQRSGPLGDQ
  PFAGLLPKNLSREELVDALRAAVVDRKGPLVTLNKPQGLPVTGKPGELTLFSVLPELSQS
  LGLREQELQVVRASGKESSGLVLLSSCPQTASRLQKYFTHARRAQRPTATYCAVTDGIPA
  ASEGKIQAALKLEHIDGVNLTVPVKAPSRKDILEGVKKTLSHFRVVATGSGCALVQLQPL
  TVFSSQLQVHMVLQLCPVLGDHMYSARVGTVLGQRFLLPAENNKPQRQVLDEALLRRLHL
  TPSQAAQLPLHLHLHRLLLPGTRARDTPVELLAPLPPYFSRTLQCLGLRLQ
• Function: Catalyzes uridine to pseudouridine isomerization (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs), a post-transcriptional modification necessary for their translation. Acts at position 390 in COXI mt-mRNA and at position 697-699 in mitochondrial COXIII mt-mRNA. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and may play a role in mitochondrial ribosome biogenesis.

Molecular Interaction Atlas (MIA) of This DOT

10 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 Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[10]
biochanin A	DM0HPWY	Investigative	biochanin A decreases the expression of Mitochondrial mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[11]

1 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 mRNA pseudouridine synthase RPUSD3 (RPUSD3).	[6]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion. J Biomed Res. 2020 Jun 30;34(5):369-378. doi: 10.7555/JBR.34.20200013.
• [11] Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate. 2002 Aug 1;52(3):201-12.