Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6BFR2U)

• DOT Name: Mitoguardin 1 (MIGA1)
• Synonyms: Protein FAM73A
• Gene Name: MIGA1
• Related Disease: Lung adenocarcinoma
• UniProt ID: MIGA1_HUMAN
• Pfam ID: PF10265
• Sequence:
  MSDCCSAPGISWEAGVGRPAVPGLELQIRRGAMSEETVSESQFSLKTAALRVFDLPLTWY
  YSLSQIKFSPVAKKLFVVTAVSAISVIFLAHHFKRKRGKKKGKILPWEPEHLILEYTKRA
  ASDKGSSCSSSRQNLTLSLSSTKDKGSQVCNYANGGLFSKYSGSAQSLASVQSVNSCHSC
  ACGNSNSWDKADEDDIKLVNIPVTTPENLYLMGMELFEEALRRWEQALTFRNRQAEDEAC
  GSIKLGAGDAIAEENVDDIISTEFIHKLEALLQRAYRLQEEFEATLGASDPNSLADDIDK
  DTDITMKGNVEDFGLRDTLSIASTDSFASAAELAEHREVRHTYSLESLCHCPFYEEAMHL
  VEEGKIYSRVLRTEMLECLGDSDFLAKLHCIRQAFQVILSESANRIFLAESGRKILSALI
  VKARKNPKKFEDVFDEMIYFLEQTDHWGSTEMELAARGVKNLNFYDVVLDFILMDSFEDL
  ENPPTSIQNVVNNRWLNSSFKETAVASSCWSVLKQKRQQMKIPDGFFAHFYAICEHISPV
  LAWGFLGPRNSLYDLCCFFKNQVLLFLKDIFDFEKVRYSSTETLAEDLMQLLIRRTELLM
  AYLEADALRHTSSCLSSHGHVMSTGLLEAKVQ
• Function: Regulator of mitochondrial fusion: acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD.
• Reactome Pathway: Synthesis of PA (R-HSA-1483166)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Limited	Genetic Variation	[1]

9 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 Mitoguardin 1 (MIGA1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitoguardin 1 (MIGA1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitoguardin 1 (MIGA1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mitoguardin 1 (MIGA1).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mitoguardin 1 (MIGA1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Mitoguardin 1 (MIGA1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mitoguardin 1 (MIGA1).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Mitoguardin 1 (MIGA1).	[8]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Mitoguardin 1 (MIGA1).	[3]

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 affects the methylation of Mitoguardin 1 (MIGA1).	[6]

References

• [1] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [2] 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.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.