Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4XR6TE)

• DOT Name: Lysophospholipid acyltransferase 1 (MBOAT1)
• Synonyms: LPLAT 1; 1-acylglycerophosphocholine O-acyltransferase; EC 2.3.1.23; 1-acylglycerophosphoethanolamine O-acyltransferase; EC 2.3.1.n7; 1-acylglycerophosphoserine O-acyltransferase MBOAT1; EC 2.3.1.n6; Lysophosphatidylserine acyltransferase; LPSAT; Lyso-PS acyltransferase; Membrane-bound O-acyltransferase domain-containing protein 1; O-acyltransferase domain-containing protein 1
• Gene Name: MBOAT1
• Related Disease:
  Brachydactyly-syndactyly syndrome
  Cholestasis
• UniProt ID: MBOA1_HUMAN
• EC Number: 2.3.1.23; 2.3.1.n6; 2.3.1.n7
• Pfam ID: PF03062
• Sequence:
  MAAEPQPSSLSYRTTGSTYLHPLSELLGIPLDQVNFVVCQLVALFAAFWFRIYLRPGTTS
  SDVRHAVATIFGIYFVIFCFGWYSVHLFVLVLMCYAIMVTASVSNIHRYSFFVAMGYLTI
  CHISRIYIFHYGILTTDFSGPLMIVTQKITTLAFQVHDGLGRRAEDLSAEQHRLAIKVKP
  SFLEYLSYLLNFMSVIAGPCNNFKDYIAFIEGKHIHMKLLEVNWKRKGFHSLPEPSPTGA
  VIHKLGITLVSLLLFLTLTKTFPVTCLVDDWFVHKASFPARLCYLYVVMQASKPKYYFAW
  TLADAVNNAAGFGFSGVDKNGNFCWDLLSNLNIWKIETATSFKMYLENWNIQTATWLKCV
  CYQRVPWYPTVLTFILSALWHGVYPGYYFTFLTGILVTLAARAVRNNYRHYFLSSRALKA
  VYDAGTWAVTQLAVSYTVAPFVMLAVEPTISLYKSMYFYLHIISLLIILFLPMKPQAHTQ
  RRPQTLNSINKRKTD
• Function: Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA towards a lysophospholipid producing a phospholipid and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle. Acts on lysophosphatidylserine (1-acyl-2-hydroxy-sn-glycero-3-phospho-L-serine or LPS) and lysophosphatidylethanolamine (1-acyl-sn-glycero-3-phosphoethanolamine or LPE), and to a lesser extend lysophosphatidylcholine. Prefers oleoyl-CoA as the acyl donor and 1-oleoyl-LPE as acceptor. May play a role in neurite outgrowth during neuronal 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 PS (R-HSA-1482801)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brachydactyly-syndactyly syndrome	DISR95WN	Limited	Genetic Variation	[1]
Cholestasis	DISDJJWE	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[8]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[9]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lysophospholipid acyltransferase 1 (MBOAT1).	[14]

References

• [1] A t(4;6)(q12;p23) translocation disrupts a membrane-associated O-acetyl transferase gene (MBOAT1) in a patient with a novel brachydactyly-syndactyly syndrome.Eur J Hum Genet. 2007 Jul;15(7):743-51. doi: 10.1038/sj.ejhg.5201833. Epub 2007 Apr 18.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [6] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [10] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] 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.
• [14] 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.