Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX65INE)

• DOT Name: 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1)
• Synonyms: EC 2.3.1.51; 1-acylglycerol-3-phosphate O-acyltransferase 1; 1-AGP acyltransferase 1; 1-AGPAT 1; Lysophosphatidic acid acyltransferase alpha; LPAAT-alpha; Protein G15
• Gene Name: AGPAT1
• UniProt ID: PLCA_HUMAN
• EC Number: 2.3.1.51
• Pfam ID: PF01553
• Sequence:
  MDLWPGAWMLLLLLFLLLLFLLPTLWFCSPSAKYFFKMAFYNGWILFLAVLAIPVCAVRG
  RNVENMKILRLMLLHIKYLYGIRVEVRGAHHFPPSQPYVVVSNHQSSLDLLGMMEVLPGR
  CVPIAKRELLWAGSAGLACWLAGVIFIDRKRTGDAISVMSEVAQTLLTQDVRVWVFPEGT
  RNHNGSMLPFKRGAFHLAVQAQVPIVPIVMSSYQDFYCKKERRFTSGQCQVRVLPPVPTE
  GLTPDDVPALADRVRHSMLTVFREISTDGRGGGDYLKKPGGGG
• Function: Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.
• Tissue Specificity: Widely expressed. Expressed in adipose tissue and at high levels in testis and pancreas. Expressed at lower levels in tissues such as heart, brain, placenta, kidney, lung, spleen, thymus, prostate, ovary, intestine, colon, leukocyte and liver.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
  Phospholipase D sig.ling pathway (hsa04072)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway:
  ChREBP activates metabolic gene expression (R-HSA-163765)
  Synthesis of PA (R-HSA-1483166)
• BioCyc Pathway: MetaCyc:HS09762-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1).	[1]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1).	[4]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1).	[5]
CITCO	DM0N634	Investigative	CITCO increases the expression of 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1).	[5]

1 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 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1).	[2]

References

• [1] 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.
• [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] 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.
• [4] 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.
• [5] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.