Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSXO9P6)

• DOT Name: Ethanolamine-phosphate phospho-lyase (ETNPPL)
• Synonyms: EC 4.2.3.2; Alanine--glyoxylate aminotransferase 2-like 1
• Gene Name: ETNPPL
• Related Disease:
  Schizophrenia
  Bipolar disorder
  Bronchopulmonary dysplasia
  Carcinoma of liver and intrahepatic biliary tract
  Fatty liver disease
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
• UniProt ID: AT2L1_HUMAN
• PDB ID: 6TOR
• EC Number: 4.2.3.2
• Pfam ID: PF00202
• Sequence:
  MCELYSKRDTLGLRKKHIGPSCKVFFASDPIKIVRAQRQYMFDENGEQYLDCINNVAHVG
  HCHPGVVKAALKQMELLNTNSRFLHDNIVEYAKRLSATLPEKLSVCYFTNSGSEANDLAL
  RLARQFRGHQDVITLDHAYHGHLSSLIEISPYKFQKGKDVKKEFVHVAPTPDTYRGKYRE
  DHADSASAYADEVKKIIEDAHNSGRKIAAFIAESMQSCGGQIIPPAGYFQKVAEYVHGAG
  GVFIADEVQVGFGRVGKHFWSFQMYGEDFVPDIVTMGKPMGNGHPVACVVTTKEIAEAFS
  SSGMEYFNTYGGNPVSCAVGLAVLDIIENEDLQGNAKRVGNYLTELLKKQKAKHTLIGDI
  RGIGLFIGIDLVKDHLKRTPATAEAQHIIYKMKEKRVLLSADGPHRNVLKIKPPMCFTEE
  DAKFMVDQLDRILTVLEEAMGTKTESVTSENTPCKTKMLKEAHIELLRDSTTDSKENPSR
  KRNGMCTDTHSLLSKRLKT
• Function: Catalyzes the pyridoxal-phosphate-dependent breakdown of phosphoethanolamine, converting it to ammonia, inorganic phosphate and acetaldehyde.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of PE (R-HSA-1483213)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Altered Expression	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[3]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Liver cancer	DISDE4BI	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]

11 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 Ethanolamine-phosphate phospho-lyase (ETNPPL).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[9]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[14]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Ethanolamine-phosphate phospho-lyase (ETNPPL).	[9]

References

• [1] Molecular identification of hydroxylysine kinase and of ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and phosphoethanolamine.J Biol Chem. 2012 Mar 2;287(10):7246-55. doi: 10.1074/jbc.M111.323485. Epub 2012 Jan 12.
• [2] Shared gene expression alterations in schizophrenia and bipolar disorder.Biol Psychiatry. 2008 Jul 15;64(2):89-97. doi: 10.1016/j.biopsych.2007.11.010. Epub 2008 Jan 11.
• [3] AGXT2L1 is down-regulated in heptocellular carcinoma and associated with abnormal lipogenesis.J Clin Pathol. 2016 Mar;69(3):215-20. doi: 10.1136/jclinpath-2015-203042. Epub 2015 Aug 20.
• [4] Lipidomic analysis of human primary hepatocytes following LXR activation with GW3965 identifies AGXT2L1 as a main target associated to changes in phosphatidylethanolamine.J Steroid Biochem Mol Biol. 2020 Apr;198:105558. doi: 10.1016/j.jsbmb.2019.105558. Epub 2019 Nov 26.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [11] 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.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.