Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCV7AGV)

• DOT Name: Lysophosphatidylcholine acyltransferase 1 (LPCAT1)
• Synonyms: LPC acyltransferase 1; LPCAT-1; LysoPC acyltransferase 1; EC 2.3.1.23; 1-acylglycerol-3-phosphate O-acyltransferase; EC 2.3.1.51; 1-acylglycerophosphocholine O-acyltransferase; 1-alkenylglycerophosphocholine O-acyltransferase; EC 2.3.1.25; 1-alkylglycerophosphocholine O-acetyltransferase; EC 2.3.1.67; Acetyl-CoA:lyso-platelet-activating factor acetyltransferase; Acetyl-CoA:lyso-PAF acetyltransferase; Lyso-PAF acetyltransferase; LysoPAFAT; Acyltransferase-like 2; Phosphonoformate immuno-associated protein 3
• Gene Name: LPCAT1
• Related Disease:
  Adenocarcinoma
  Breast carcinoma
  Breast fibrocystic disease
  Cardiac arrest
  Clear cell renal carcinoma
  Cystic fibrosis
  Ductal breast carcinoma in situ
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Oral cancer
  Retinitis pigmentosa
  Advanced cancer
  Leber congenital amaurosis
  Neoplasm
  Castration-resistant prostate carcinoma
  Prostate cancer
  Prostate carcinoma
  Sickle-cell anaemia
• UniProt ID: PCAT1_HUMAN
• EC Number: 2.3.1.23; 2.3.1.25; 2.3.1.51; 2.3.1.67
• Pfam ID: PF01553 ; PF13833
• Sequence:
  MRLRGCGPRAAPASSAGASDARLLAPPGRNPFVHELRLSALQKAQVALMTLTLFPVRLLV
  AAAMMLLAWPLALVASLGSAEKEPEQPPALWRKVVDFLLKAIMRTMWFAGGFHRVAVKGR
  QALPTEAAILTLAPHSSYFDAIPVTMTMSSIVMKAESRDIPIWGTLIQYIRPVFVSRSDQ
  DSRRKTVEEIKRRAQSNGKWPQIMIFPEGTCTNRTCLITFKPGAFIPGAPVQPVVLRYPN
  KLDTITWTWQGPGALEILWLTLCQFHNQVEIEFLPVYSPSEEEKRNPALYASNVRRVMAE
  ALGVSVTDYTFEDCQLALAEGQLRLPADTCLLEFARLVRGLGLKPEKLEKDLDRYSERAR
  MKGGEKIGIAEFAASLEVPVSDLLEDMFSLFDESGSGEVDLRECVVALSVVCRPARTLDT
  IQLAFKMYGAQEDGSVGEGDLSCILKTALGVAELTVTDLFRAIDQEEKGKITFADFHRFA
  EMYPAFAEEYLYPDQTHFESCAETSPAPIPNGFCADFSPENSDAGRKPVRKKLD
• Function: Exhibits acyltransferase activity. Exhibits acetyltransferase activity. Activity is calcium-independent. Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC). Catalyzes the conversion 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. Displays a clear preference for saturated fatty acyl-CoAs, and 1-myristoyl or 1-palmitoyl LPC as acyl donors and acceptors, respectively. Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF). May synthesize phosphatidylcholine in pulmonary surfactant, thereby playing a pivotal role in respiratory physiology. Involved in the regulation of lipid droplet number and size.
• Tissue Specificity: Erythrocytes.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Ether lipid metabolism (hsa00565)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Acyl chain remodelling of PG (R-HSA-1482925)
  Synthesis of PA (R-HSA-1483166)
  Synthesis of PC (R-HSA-1483191)
  Neutrophil degranulation (R-HSA-6798695)
  Acyl chain remodelling of PC (R-HSA-1482788)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Breast fibrocystic disease	DISUM7ID	Strong	Altered Expression	[3]
Cardiac arrest	DIS9DIA4	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[5]
Cystic fibrosis	DIS2OK1Q	Strong	Altered Expression	[3]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Altered Expression	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[1]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Oral cancer	DISLD42D	Strong	Biomarker	[8]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[9]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[4]
Leber congenital amaurosis	DISMGH8F	moderate	Biomarker	[10]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[11]
Prostate cancer	DISF190Y	Limited	Altered Expression	[12]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[12]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Lysophosphatidylcholine acyltransferase 1 (LPCAT1) affects the response to substance of Doxorubicin.	[25]

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 Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[19]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[23]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[24]

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 Lysophosphatidylcholine acyltransferase 1 (LPCAT1).	[17]

References

• [1] Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci.Carcinogenesis. 2016 Jan;37(1):96-105. doi: 10.1093/carcin/bgv165. Epub 2015 Nov 20.
• [2] Up-regulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) is linked to poor prognosis in breast cancer.Aging (Albany NY). 2019 Sep 18;11(18):7796-7804. doi: 10.18632/aging.102287. Epub 2019 Sep 18.
• [3] Lysophosphatidylcholine acyltransferase 1 (LPCAT1) upregulation in breast carcinoma contributes to tumor progression and predicts early tumor recurrence.Tumour Biol. 2015 Jul;36(7):5473-83. doi: 10.1007/s13277-015-3214-8. Epub 2015 Feb 16.
• [4] LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway.J Exp Clin Cancer Res. 2019 Feb 21;38(1):95. doi: 10.1186/s13046-019-1092-4.
• [5] Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma.J Exp Clin Cancer Res. 2017 May 12;36(1):66. doi: 10.1186/s13046-017-0525-1.
• [6] Lysophosphatidylcholine acyltransferase 1 is downregulated by hepatitis C virus: impact on production of lipo-viro-particles.Gut. 2017 Dec;66(12):2160-2169. doi: 10.1136/gutjnl-2016-311508. Epub 2016 Aug 31.
• [7] Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression.J Hepatol. 2013 Aug;59(2):292-9. doi: 10.1016/j.jhep.2013.02.030. Epub 2013 Apr 6.
• [8] Lysophosphatidylcholine acyltransferase1 overexpression promotes oral squamous cell carcinoma progression via enhanced biosynthesis of platelet-activating factor.PLoS One. 2015 Mar 24;10(3):e0120143. doi: 10.1371/journal.pone.0120143. eCollection 2015.
• [9] Molecular screening of the LPCAT1 gene in patients with retinitis pigmentosa without defined mutations in known retinitis pigmentosa genes.Mol Med Rep. 2015 Oct;12(4):5983-8. doi: 10.3892/mmr.2015.4204. Epub 2015 Aug 10.
• [10] Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice.Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15523-8. doi: 10.1073/pnas.1002897107. Epub 2010 Aug 16.
• [11] Effects of platelet-activating factor and its differential regulation by androgens and steroid hormones in prostate cancers.Br J Cancer. 2013 Sep 3;109(5):1279-86. doi: 10.1038/bjc.2013.480. Epub 2013 Aug 15.
• [12] High lysophosphatidylcholine acyltransferase 1 expression independently predicts high risk for biochemical recurrence in prostate cancers.Mol Oncol. 2013 Dec;7(6):1001-11. doi: 10.1016/j.molonc.2013.07.009. Epub 2013 Jul 19.
• [13] Hypoxia-mediated impaired erythrocyte Lands' Cycle is pathogenic for sickle cell disease.Sci Rep. 2016 Jul 20;6:29637. doi: 10.1038/srep29637.
• [14] 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.
• [15] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [16] 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.
• [17] 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.
• [18] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [19] 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.
• [20] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [21] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [22] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [23] 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.
• [24] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [25] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.