Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVA8XFH)

• DOT Name: Pseudouridylate synthase RPUSD2 (RPUSD2)
• Synonyms: EC 5.4.99.-; RNA pseudouridylate synthase domain-containing protein 2
• Gene Name: RPUSD2
• Related Disease: Herpes simplex infection
• UniProt ID: RUSD2_HUMAN
• EC Number: 5.4.99.-
• Pfam ID: PF00849
• Sequence:
  MWLDRRGWLRVLGHWRYDLRRPSFTRTWSGDKGPMAETVSTQVGTEGGLRASHQQNGDAG
  GDAKVELSPGPPKPAGREVEPAPVGGEHPSAAAPGPGKHKKRRGATRERVVPPPKKRRTG
  VSFGDEHFAETSYYFEGGLRKVRPYYFDFRTYCKGRWVGHSLLHVFSTEFRAQPLAYYEA
  AVRAGRLQLNEKPVQDLNIVLKDNDFLRNTVHRHEPPVTAEPIRLLAENEDVVVVDKPSS
  IPVHPCGRFRHNTVIFILGKEHQLKELHPLHRLDRLTSGVLMFAKTAAVSERIHEQVRDR
  QLEKEYVCRVEGEFPTEEVTCKEPILVVSYKVGVCRVDPRGKPCETVFQRLSYNGQSSVV
  RCRPLTGRTHQIRVHLQFLGHPILNDPIYNSVAWGPSRGRGGYIPKTNEELLRDLVAEHQ
  AKQSLDVLDLCEGDLSPGLTDSTAPSSELGKDDLEELAAAAQKMEEVAEAAPQELDTIAL
  ASEKAVETDVMNQETDPLCAECRLVRQDPLPQDLVMFLHALRYKGPGFEYFSPMPAWAQD
  DWQKD
• Function: Pseudouridine synthase that catalyzes pseudouridylation of mRNAs.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[1]

9 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 Pseudouridylate synthase RPUSD2 (RPUSD2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Pseudouridylate synthase RPUSD2 (RPUSD2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Pseudouridylate synthase RPUSD2 (RPUSD2).	[10]

References

• [1] The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons.J Virol. 2015 Dec 9;90(4):2102-11. doi: 10.1128/JVI.03041-15. Print 2016 Feb 15.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [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] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.