Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYPQJC8)

• DOT Name: Plasmanylethanolamine desaturase 1 (PEDS1)
• Synonyms: EC 1.14.19.77; Transmembrane protein 189
• Gene Name: PEDS1
• UniProt ID: PDES1_HUMAN
• EC Number: 1.14.19.77
• Pfam ID: PF10520
• Sequence:
  MAGAENWPGQQLELDEDEASCCRWGAQHAGARELAALYSPGKRLQEWCSVILCFSLIAHN
  LVHLLLLARWEDTPLVILGVVAGALIADFLSGLVHWGADTWGSVELPIVGKAFIRPFREH
  HIDPTAITRHDFIETNGDNCLVTLLPLLNMAYKFRTHSPEALEQLYPWECFVFCLIIFGT
  FTNQIHKWSHTYFGLPRWVTLLQDWHVILPRKHHRIHHVSPHETYFCITTGWLNYPLEKI
  GFWRRLEDLIQGLTGEKPRADDMKWAQKIK
• Function: Plasmanylethanolamine desaturase involved in plasmalogen biogenesis in the endoplasmic reticulum membrane. Plasmalogens are glycerophospholipids with a hydrocarbon chain linked by a vinyl ether bond at the glycerol sn-1 position, and are involved in antioxidative and signaling mechanisms.
• KEGG Pathway:
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
• BioCyc Pathway: MetaCyc:G66-30744-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 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 Plasmanylethanolamine desaturase 1 (PEDS1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Plasmanylethanolamine desaturase 1 (PEDS1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Plasmanylethanolamine desaturase 1 (PEDS1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Plasmanylethanolamine desaturase 1 (PEDS1).	[8]

5 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 Plasmanylethanolamine desaturase 1 (PEDS1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Plasmanylethanolamine desaturase 1 (PEDS1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Plasmanylethanolamine desaturase 1 (PEDS1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Plasmanylethanolamine desaturase 1 (PEDS1).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Plasmanylethanolamine desaturase 1 (PEDS1).	[9]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] 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.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.