Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWP3WLV)

• DOT Name: PRELI domain-containing protein 1, mitochondrial (PRELID1)
• Synonyms: 25 kDa protein of relevant evolutionary and lymphoid interest; Px19-like protein
• Gene Name: PRELID1
• Related Disease: Advanced cancer
• UniProt ID: PRLD1_HUMAN
• PDB ID: 6I3V; 6I3Y
• Pfam ID: PF04707
• Sequence:
  MVKYFLGQSVLRSSWDQVFAAFWQRYPNPYSKHVLTEDIVHREVTPDQKLLSRRLLTKTN
  RMPRWAERLFPANVAHSVYVLEDSIVDPQNQTMTTFTWNINHARLMVVEERCVYCVNSDN
  SGWTEIRREAWVSSSLFGVSRAVQEFGLARFKSNVTKTMKGFEYILAKLQGEAPSKTLVE
  TAKEAKEKAKETALAATEKAKDLASKAATKKQQQQQQFV
• Function: Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane. Regulates the mitochondrial apoptotic pathway in primary Th cells. Regulates Th cell differentiation by down-regulating STAT6 thereby reducing IL-4-induced Th2 cell number. May be important for the development of vital and immunocompetent organs.
• Tissue Specificity: Highly expressed in fetal liver; less expressed in fetal brain, lung, and kidney. At the adult stage, expression is drastically reduced in the liver but highly expressed in the spleen, brain, lung, lymph nodes and peripheral blood leukocytes.
• Reactome Pathway: TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of PRELI domain-containing protein 1, mitochondrial (PRELID1).	[8]

References

• [1] Alternative Polyadenylation of PRELID1 Regulates Mitochondrial ROS Signaling and Cancer Outcomes.Mol Cancer Res. 2017 Dec;15(12):1741-1751. doi: 10.1158/1541-7786.MCR-17-0010. Epub 2017 Sep 14.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.