Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKXV29C)

• DOT Name: Pseudouridylate synthase PUS7L (PUS7L)
• Synonyms: EC 5.4.99.-; Pseudouridylate synthase 7 homolog-like protein
• Gene Name: PUS7L
• UniProt ID: PUS7L_HUMAN
• EC Number: 5.4.99.-
• Pfam ID: PF01142
• Sequence:
  MEEDTDYRIRFSSLCFFNDHVGFHGTIKSSPSDFIVIEIDEQGQLVNKTIDEPIFKISEI
  QLEPNNFPKKPKLDLQNLSLEDGRNQEVHTLIKYTDGDQNHQSGSEKEDTIVDGTSKCEE
  KADVLSSFLDEKTHELLNNFACDVREKWLSKTELIGLPPEFSIGRILDKNQRASLHSAIR
  QKFPFLVTVGKNSEIVVKPNLEYKELCHLVSEEEAFDFFKYLDAKKENSKFTFKPDTNKD
  HRKAVHHFVNKKFGNLVETKSFSKMNCSAGNPNVVVTVRFREKAHKRGKRPLSECQEGKV
  IYTAFTLRKENLEMFEAIGFLAIKLGVIPSDFSYAGLKDKKAITYQAMVVRKVTPERLKN
  IEKEIEKKRMNVFNIRSVDDSLRLGQLKGNHFDIVIRNLKKQINDSANLRERIMEAIENV
  KKKGFVNYYGPQRFGKGRKVHTDQIGLALLKNEMMKAIKLFLTPEDLDDPVNRAKKYFLQ
  TEDAKGTLSLMPEFKVRERALLEALHRFGMTEEGCIQAWFSLPHSMRIFYVHAYTSKIWN
  EAVSYRLETYGARVVQGDLVCLDEDIDDENFPNSKIHLVTEEEGSANMYAIHQVVLPVLG
  YNIQYPKNKVGQWYHDILSRDGLQTCRFKVPTLKLNIPGCYRQILKHPCNLSYQLMEDHD
  IDVKTKGSHIDETALSLLISFDLDASCYATVCLKEIMKHDV
• Function: Pseudouridine synthase that catalyzes pseudouridylation of mRNAs.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pseudouridylate synthase PUS7L (PUS7L).	[1]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Pseudouridylate synthase PUS7L (PUS7L).	[12]

11 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 Pseudouridylate synthase PUS7L (PUS7L).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Pseudouridylate synthase PUS7L (PUS7L).	[13]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [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] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] 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.
• [13] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.