Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWAJH76)

• DOT Name: PRELI domain containing protein 3A (PRELID3A)
• Synonyms: Protein slowmo homolog 1
• Gene Name: PRELID3A
• UniProt ID: PLD3A_HUMAN
• PDB ID: 4XZV; 8AG0
• Pfam ID: PF04707
• Sequence:
  MKIWSSEHVFGHPWDTVIQAAMRKYPNPMNPSVLGVDVLQRRVDGRGRLHSLRLLSTEWG
  LPSLVRAILGTSRTLTYIREHSVVDPVEKKMELCSTNITLTNLVSVNERLVYTPHPENPE
  MTVLTQEAIITVKGISLGSYLESLMANTISSNAKKGWAAIEWIIEHSESAVS
• Function: In vitro, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space. Phosphatidic acid import is required for cardiolipin (CL) synthesis in the mitochondrial inner membrane.
• Reactome Pathway: TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of PRELI domain containing protein 3A (PRELID3A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PRELI domain containing protein 3A (PRELID3A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PRELI domain containing protein 3A (PRELID3A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PRELI domain containing protein 3A (PRELID3A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PRELI domain containing protein 3A (PRELID3A).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of PRELI domain containing protein 3A (PRELID3A).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of PRELI domain containing protein 3A (PRELID3A).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PRELI domain containing protein 3A (PRELID3A).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of PRELI domain containing protein 3A (PRELID3A).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PRELI domain containing protein 3A (PRELID3A).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PRELI domain containing protein 3A (PRELID3A).	[9]

References

• [1] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.