Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOFA3BU)

• DOT Name: tRNA pseudouridine synthase-like 1 (PUSL1)
• Synonyms: EC 5.4.99.-; tRNA pseudouridylate synthase-like 1; tRNA-uridine isomerase-like 1
• Gene Name: PUSL1
• Related Disease: Systemic lupus erythematosus
• UniProt ID: PUSL1_HUMAN
• EC Number: 5.4.99.-
• Pfam ID: PF01416
• Sequence:
  MSSAPASGSVRARYLVYFQYVGTDFNGVAAVRGTQRAVGVQNYLEEAAERLNSVEPVRFT
  ISSRTDAGVHALSNAAHLDVQRRSGRPPFPPEVLAEALNTHLRHPAIRVLRAFRVPSDFH
  ARHAATSRTYLYRLATGCHRRDELPVFERNLCWTLPADCLDMVAMQEAAQHLLGTHDFSA
  FQSAGSPVPSPVRTLRRVSVSPGQASPLVTPEESRKLRFWNLEFESQSFLYRQVRRMTAV
  LVAVGLGALAPAQVKTILESQDPLGKHQTRVAPAHGLFLKSVLYGNLGAASCTLQGPQFG
  SHG

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[1]

2 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 pseudouridine synthase-like 1 (PUSL1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of tRNA pseudouridine synthase-like 1 (PUSL1).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of tRNA pseudouridine synthase-like 1 (PUSL1).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of tRNA pseudouridine synthase-like 1 (PUSL1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of tRNA pseudouridine synthase-like 1 (PUSL1).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of tRNA pseudouridine synthase-like 1 (PUSL1).	[7]

References

• [1] Transancestral mapping and genetic load in systemic lupus erythematosus.Nat Commun. 2017 Jul 17;8:16021. doi: 10.1038/ncomms16021.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.