Details of Drug Off-Target (DOT)

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

• DOT Name: Lysophospholipid acyltransferase LPCAT4 (LPCAT4)
• Synonyms: 1-acylglycerol-3-phosphate O-acyltransferase 7; 1-AGP acyltransferase 7; 1-AGPAT 7; 1-acylglycerophosphocholine O-acyltransferase; EC 2.3.1.23; 1-acylglycerophosphoserine O-acyltransferase; EC 2.3.1.n6; 1-alkenylglycerophosphoethanolamine O-acyltransferase; EC 2.3.1.121; 1-alkylglycerophosphocholine O-acetyltransferase; EC 2.3.1.67; Acyltransferase-like 3; Lysophosphatidylcholine acyltransferase 4; Lysophosphatidylethanolamine acyltransferase 2; EC 2.3.1.n7; Plasmalogen synthase
• Gene Name: LPCAT4
• Related Disease: Colorectal carcinoma
• UniProt ID: LPCT4_HUMAN
• EC Number: 2.3.1.121; 2.3.1.23; 2.3.1.67; 2.3.1.n6; 2.3.1.n7
• Pfam ID: PF01553
• Sequence:
  MSQGSPGDWAPLDPTPGPPASPNPFVHELHLSRLQRVKFCLLGALLAPIRVLLAFIVLFL
  LWPFAWLQVAGLSEEQLQEPITGWRKTVCHNGVLGLSRLLFFLLGFLRIRVRGQRASRLQ
  APVLVAAPHSTFFDPIVLLPCDLPKVVSRAENLSVPVIGALLRFNQAILVSRHDPASRRR
  VVEEVRRRATSGGKWPQVLFFPEGTCSNKKALLKFKPGAFIAGVPVQPVLIRYPNSLDTT
  SWAWRGPGVLKVLWLTASQPCSIVDVEFLPVYHPSPEESRDPTLYANNVQRVMAQALGIP
  ATECEFVGSLPVIVVGRLKVALEPQLWELGKVLRKAGLSAGYVDAGAEPGRSRMISQEEF
  ARQLQLSDPQTVAGAFGYFQQDTKGLVDFRDVALALAALDGGRSLEELTRLAFELFAEEQ
  AEGPNRLLYKDGFSTILHLLLGSPHPAATALHAELCQAGSSQGLSLCQFQNFSLHDPLYG
  KLFSTYLRPPHTSRGTSQTPNASSPGNPTALANGTVQAPKQKGD
• Function: Displays acyl-CoA-dependent lysophospholipid acyltransferase activity with a subset of lysophospholipids as substrates; converts lysophosphatidylethanolamine to phosphatidylethanolamine, lysophosphatidylcholine to phosphatidycholine, 1-alkenyl-lysophatidylethanolamine to 1-alkenyl-phosphatidylethanolamine, lysophosphatidylglycerol and alkyl-lysophosphatidylcholine to phosphatidylglycerol and alkyl-phosphatidylcholine, respectively. In contrast, has no lysophosphatidylinositol, glycerol-3-phosphate, diacylglycerol or lysophosphatidic acid acyltransferase activity. Prefers long chain acyl-CoAs (C16, C18) as acyl donors.
• Tissue Specificity: Widely expressed with predominant level in brain.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Acyl chain remodelling of PS (R-HSA-1482801)
  Acyl chain remodelling of PE (R-HSA-1482839)
  Acyl chain remodelling of PG (R-HSA-1482925)
  Synthesis of PA (R-HSA-1483166)
  Acyl chain remodelling of PC (R-HSA-1482788)
• BioCyc Pathway: MetaCyc:HS16664-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[8]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Lysophospholipid acyltransferase LPCAT4 (LPCAT4).	[11]

References

• [1] Accumulated phosphatidylcholine (16:0/16:1) in human colorectal cancer; possible involvement of LPCAT4.Cancer Sci. 2013 Oct;104(10):1295-302. doi: 10.1111/cas.12221. Epub 2013 Jul 30.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] 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.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
• [10] 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.
• [11] 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.