Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZI3BXD)

• DOT Name: Lysophospholipid acyltransferase 2 (MBOAT2)
• Synonyms: LPLAT 2; EC 2.3.1.-; 1-acylglycerophosphate O-acyltransferase MBOAT2; EC 2.3.1.51; 1-acylglycerophosphocholine O-acyltransferase MBOAT2; EC 2.3.1.23; 1-acylglycerophosphoethanolamine MBOAT2 O-acyltransferase; EC 2.3.1.n7; Lysophosphatidic acid acyltransferase; LPAAT; Lyso-PA acyltransferase; Lysophosphatidylcholine acyltransferase; LPCAT; Lyso-PC acyltransferase; Lysophosphatidylcholine acyltransferase 4; Lyso-PC acyltransferase 4; Lysophosphatidylethanolamine acyltransferase; LPEAT; Lyso-PE acyltransferase; Membrane-bound O-acyltransferase domain-containing protein 2; O-acyltransferase domain-containing protein 2
• Gene Name: MBOAT2
• Related Disease: Adrenomyeloneuropathy
• UniProt ID: MBOA2_HUMAN
• EC Number: 2.3.1.-; 2.3.1.23; 2.3.1.51; 2.3.1.n7
• Pfam ID: PF03062
• Sequence:
  MATTSTTGSTLLQPLSNAVQLPIDQVNFVVCQLFALLAAIWFRTYLHSSKTSSFIRHVVA
  TLLGLYLALFCFGWYALHFLVQSGISYCIMIIIGVENMHNYCFVFALGYLTVCQVTRVYI
  FDYGQYSADFSGPMMIITQKITSLACEIHDGMFRKDEELTSSQRDLAVRRMPSLLEYLSY
  NCNFMGILAGPLCSYKDYITFIEGRSYHITQSGENGKEETQYERTEPSPNTAVVQKLLVC
  GLSLLFHLTICTTLPVEYNIDEHFQATASWPTKIIYLYISLLAARPKYYFAWTLADAINN
  AAGFGFRGYDENGAARWDLISNLRIQQIEMSTSFKMFLDNWNIQTALWLKRVCYERTSFS
  PTIQTFILSAIWHGVYPGYYLTFLTGVLMTLAARAMRNNFRHYFIEPSQLKLFYDVITWI
  VTQVAISYTVVPFVLLSIKPSLTFYSSWYYCLHILGILVLLLLPVKKTQRRKNTHENIQL
  SQSKKFDEGENSLGQNSFSTTNNVCNQNQEIASRHSSLKQ
• Function: Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophospholipid leading to the production of a phospholipid and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle. Catalyzes preferentially the acylation of lysophosphatidylethanolamine (1-acyl-sn-glycero-3-phosphoethanolamine or LPE) and lysophosphatidic acid (LPA) and to a lesser extend lysophosphatidylcholine (LPC) and lysophosphatidylserine (LPS). Prefers oleoyl-CoA as the acyl donor. May be involved in chondrocyte differentiation.
• Tissue Specificity: Expressed in neutrophils.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Acyl chain remodelling of PE (R-HSA-1482839)
  Acyl chain remodelling of PC (R-HSA-1482788)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adrenomyeloneuropathy	DISPTS3P	moderate	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 2 (MBOAT2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[11]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Lysophospholipid acyltransferase 2 (MBOAT2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lysophospholipid acyltransferase 2 (MBOAT2).	[10]

References

• [1] Integrative lipidomic and transcriptomic analysis of X-linked adrenoleukodystrophy reveals distinct lipidome signatures between adrenomyeloneuropathy and childhood cerebral adrenoleukodystrophy.Biochem Biophys Res Commun. 2019 Jan 8;508(2):563-569. doi: 10.1016/j.bbrc.2018.11.123. Epub 2018 Nov 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] 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.
• [5] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [6] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] 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.
• [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.
• [12] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.