Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNSZSH7)

DOT Name DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68)
Synonyms DIESL; EC 2.3.1.-; 2-acylglycerol/1,2-diacylglycerol O-acyltransferase; Monoacylglycerol/Diacylglycerol O-acyltransferase; MGAT/DGAT; EC 2.3.1.20, EC 2.3.1.22; Transmembrane protein 68
Gene Name TMEM68
UniProt ID
DIESL_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.1.-; 2.3.1.20; 2.3.1.22
Pfam ID
PF01553
Sequence
MIDKNQTCGVGQDSVPYMICLIHILEEWFGVEQLEDYLNFANYLLWVFTPLILLILPYFT
IFLLYLTIIFLHIYKRKNVLKEAYSHNLWDGARKTVATLWDGHAAVWHGYEVHGMEKIPE
DGPALIIFYHGAIPIDFYYFMAKIFIHKGRTCRVVADHFVFKIPGFSLLLDVFCALHGPR
EKCVEILRSGHLLAISPGGVREALISDETYNIVWGHRRGFAQVAIDAKVPIIPMFTQNIR
EGFRSLGGTRLFRWLYEKFRYPFAPMYGGFPVKLRTYLGDPIPYDPQITAEELAEKTKNA
VQALIDKHQRIPGNIMSALLERFH
Function
Catalytic subunit of the alternative triglyceride biosynthesis pathway, which mediates formation of triacylglycerol from diacylglycerol and membrane phospholipids. Synthesizes triacylglycerol at the expense of membrane phospholipids, such as phosphatidylcholine (PC) and its ether-linked form (ePC), thereby altering the composition of membranes. The alternative triglyceride biosynthesis pathway is probably required to provide the energy required for rapid growth when fuel sources are limiting. It maintains mitochondrial function during periods of extracellular lipid starvation. Can also use acyl-CoA as donor: acts as a acyl-CoA:monoacylglycerol acyltransferase (MGAT), but also shows acyl-CoA:diacylglycerol acyltransferase (DGAT) activity.

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 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 DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [1]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [2]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [3]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [4]
Quercetin DM3NC4M Approved Quercetin increases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [5]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [6]
Testosterone DM7HUNW Approved Testosterone decreases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [7]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the mutagenesis of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [9]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [10]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [11]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of DGAT1/2-independent enzyme synthesizing storage lipids (TMEM68). [12]
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⏷ Show the Full List of 12 Drug(s)

References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 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.
3 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
4 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
5 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
6 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.
7 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.
8 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
9 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
10 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.
11 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.
12 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.