Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0C22ET)

• DOT Name: Glycerol-3-phosphate acyltransferase 4 (GPAT4)
• Synonyms: EC 2.3.1.15; 1-acylglycerol-3-phosphate O-acyltransferase 6; 1-AGP acyltransferase 6; 1-AGPAT 6; Acyl-CoA:glycerol-3-phosphate acyltransferase 4; Lysophosphatidic acid acyltransferase zeta; LPAAT-zeta; Testis spermatogenesis apoptosis-related protein 7; TSARG7
• Gene Name: GPAT4
• UniProt ID: GPAT4_HUMAN
• EC Number: 2.3.1.15
• Pfam ID: PF01553
• Sequence:
  MFLLLPFDSLIVNLLGISLTVLFTLLLVFIIVPAIFGVSFGIRKLYMKSLLKIFAWATLR
  MERGAKEKNHQLYKPYTNGIIAKDPTSLEEEIKEIRRSGSSKALDNTPEFELSDIFYFCR
  KGMETIMDDEVTKRFSAEELESWNLLSRTNYNFQYISLRLTVLWGLGVLIRYCFLLPLRI
  ALAFTGISLLVVGTTVVGYLPNGRFKEFMSKHVHLMCYRICVRALTAIITYHDRENRPRN
  GGICVANHTSPIDVIILASDGYYAMVGQVHGGLMGVIQRAMVKACPHVWFERSEVKDRHL
  VAKRLTEHVQDKSKLPILIFPEGTCINNTSVMMFKKGSFEIGATVYPVAIKYDPQFGDAF
  WNSSKYGMVTYLLRMMTSWAIVCSVWYLPPMTREADEDAVQFANRVKSAIARQGGLVDLL
  WDGGLKREKVKDTFKEEQQKLYSKMIVGNHKDRSRS
• Function: Converts glycerol-3-phosphate to 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) by incorporating an acyl moiety at the sn-1 position of the glycerol backbone. Active against both saturated and unsaturated long-chain fatty acyl-CoAs. Protects cells against lipotoxicity.
• Tissue Specificity: Ubiquitous. High levels in testis. Relatively high level of expression in skeletal muscle and heart. Relatively low level of expression in lung.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of PA (R-HSA-1483166)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorpyrifos	DMKPUI6	Investigative	Glycerol-3-phosphate acyltransferase 4 (GPAT4) decreases the response to substance of Chlorpyrifos.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glycerol-3-phosphate acyltransferase 4 (GPAT4).	[1]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glycerol-3-phosphate acyltransferase 4 (GPAT4).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glycerol-3-phosphate acyltransferase 4 (GPAT4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Glycerol-3-phosphate acyltransferase 4 (GPAT4).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glycerol-3-phosphate acyltransferase 4 (GPAT4).	[5]

References

• [1] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [2] 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.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] 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.
• [5] 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.
• [6] Application of human haploid cell genetic screening model in identifying the genes required for resistance to environmental toxicants: Chlorpyrifos as a case study. J Pharmacol Toxicol Methods. 2015 Nov-Dec;76:76-82. doi: 10.1016/j.vascn.2015.08.154. Epub 2015 Aug 20.