Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNY343A)

• DOT Name: tRNA-dihydrouridine(47) synthase -like (DUS3L)
• Synonyms: EC 1.3.1.89; mRNA-dihydrouridine synthase DUS3L; EC 1.3.1.-; tRNA-dihydrouridine synthase 3-like
• Gene Name: DUS3L
• UniProt ID: DUS3L_HUMAN
• EC Number: 1.3.1.-; 1.3.1.89
• Pfam ID: PF01207
• Sequence:
  MAEGTAEAPLENGGGGDSGAGALERGVAPIKRQYLTTKEQFHQFLEAKGQEKTCRETEVG
  DPAGNELAEPEAKRIRLEDGQTADGQTEEAAEPGEQLQTQKRARGQNKGRPHVKPTNYDK
  NRLCPSLIQESAAKCFFGDRCRFLHDVGRYLETKPADLGPRCVLFETFGRCPYGVTCRFA
  GAHLRPEGQNLVQEELAARGTQPPSIRNGLDKALQQQLRKREVRFERAEQALRRFSQGPT
  PAAAVPEGTAAEGAPRQENCGAQQVPAGPGTSTPPSSPVRTCGPLTDEDVVRLRPCEKKR
  LDIRGKLYLAPLTTCGNLPFRRICKRFGADVTCGEMAVCTNLLQGQMSEWALLKRHQCED
  IFGVQLEGAFPDTMTKCAELLSRTVEVDFVDINVGCPIDLVYKKGGGCALMNRSTKFQQI
  VRGMNQVLDVPLTVKIRTGVQERVNLAHRLLPELRDWGVALVTLHGRSREQRYTKLADWQ
  YIEECVQAASPMPLFGNGDILSFEDANRAMQTGVTGIMIARGALLKPWLFTEIKEQRHWD
  ISSSERLDILRDFTNYGLEHWGSDTQGVEKTRRFLLEWLSFLCRYVPVGLLERLPQRINE
  RPPYYLGRDYLETLMASQKAADWIRISEMLLGPVPPSFAFLPKHKANAYK
• Function: Catalyzes the synthesis of dihydrouridine, a modified base, in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Mainly modifies the uridine in position 47 (U47) in the D-loop of most cytoplasmic tRNAs. Also able to mediate the formation of dihydrouridine in some mRNAs, thereby regulating their translation.

Molecular Interaction Atlas (MIA) of This DOT

4 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 tRNA-dihydrouridine(47) synthase -like (DUS3L).	[1]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of tRNA-dihydrouridine(47) synthase -like (DUS3L).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of tRNA-dihydrouridine(47) synthase -like (DUS3L).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of tRNA-dihydrouridine(47) synthase -like (DUS3L).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of tRNA-dihydrouridine(47) synthase -like (DUS3L).	[2]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of tRNA-dihydrouridine(47) synthase -like (DUS3L).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of tRNA-dihydrouridine(47) synthase -like (DUS3L).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of tRNA-dihydrouridine(47) synthase -like (DUS3L).	[7]

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] 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.
• [3] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [4] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [5] 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.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.