Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR3RQ6I)

• DOT Name: 18S rRNA aminocarboxypropyltransferase (TSR3)
• Synonyms: EC 2.5.1.-; 20S S rRNA accumulation protein 3 homolog; HsTsr3
• Gene Name: TSR3
• UniProt ID: TSR3_HUMAN
• EC Number: 2.5.1.-
• Pfam ID: PF04034 ; PF04068
• Sequence:
  MGRRRAARGPGAEGGRPRHLPTRSLEAFAEEVGAALQASVEPGAADGEGGPGPAALPCTL
  AMWELGHCDPRRCTGRKLARLGLVRCLRLGHRFGGLVLSPVGKQYASPADRQLVAQSGVA
  VIDCSWARLDETPFGKMRGSHLRLLPYLVAANPVNYGRPYRLSCVEAFAATFCIVGFPDL
  AVILLRKFKWGKGFLDLNRQLLDKYAACGSPEEVLQAEQEFLANAKESPQEEEIDPFDVD
  SGREFGNPNRPVASTRLPSDTDDSDASEDPGPGAERGGASSSCCEEEQTQGRGAEARAPA
  EVWKGIKKRQRD
• Function: Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA (Probable). It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) conserved in eukaryotic 18S rRNA (Probable).
• Reactome Pathway: rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

1 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 18S rRNA aminocarboxypropyltransferase (TSR3).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 18S rRNA aminocarboxypropyltransferase (TSR3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of 18S rRNA aminocarboxypropyltransferase (TSR3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 18S rRNA aminocarboxypropyltransferase (TSR3).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of 18S rRNA aminocarboxypropyltransferase (TSR3).	[5]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of 18S rRNA aminocarboxypropyltransferase (TSR3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 18S rRNA aminocarboxypropyltransferase (TSR3).	[6]

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] 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] 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.
• [6] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.