Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV3E4GU)

• DOT Name: Mitochondrial carrier homolog 2 (MTCH2)
• Synonyms: Met-induced mitochondrial protein
• Gene Name: MTCH2
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Anxiety
  Cardiovascular disease
  Hyperinsulinemia
  Niemann-Pick disease, type C1
• UniProt ID: MTCH2_HUMAN
• Pfam ID: PF00153
• Sequence:
  MADAASQVLLGSGLTILSQPLMYVKVLIQVGYEPLPPTIGRNIFGRQVCQLPGLFSYAQH
  IASIDGRRGLFTGLTPRLCSGVLGTVVHGKVLQHYQESDKGEELGPGNVQKEVSSSFDHV
  IKETTREMIARSAATLITHPFHVITLRSMVQFIGRESKYCGLCDSIITIYREEGILGFFA
  GLVPRLLGDILSLWLCNSLAYLVNTYALDSGVSTMNEMKSYSQAVTGFFASMLTYPFVLV
  SNLMAVNNCGLAGGCPPYSPIYTSWIDCWCMLQKEGNMSRGNSLFFRKVPFGKTYCCDLK
  MLI
• Function: Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane. Catalyzes insertion of proteins with alpha-helical transmembrane regions, such as signal-anchored, tail-anchored and multi-pass membrane proteins. Does not mediate insertion of beta-barrel transmembrane proteins. Also acts as a receptor for the truncated form of pro-apoptotic BH3-interacting domain death agonist (p15 BID) and has therefore a critical function in apoptosis. Regulates the quiescence/cycling of hematopoietic stem cells (HSCs). Acts as a regulator of mitochondrial fusion, essential for the naive-to-primed interconversion of embryonic stem cells (ESCs). Acts as a regulator of lipid homeostasis and has a regulatory role in adipocyte differentiation and biology.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Anxiety	DISIJDBA	Strong	Genetic Variation	[3]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[4]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[5]
Niemann-Pick disease, type C1	DIS9HUE3	Strong	Biomarker	[6]

14 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 Mitochondrial carrier homolog 2 (MTCH2).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[17]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[19]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Mitochondrial carrier homolog 2 (MTCH2).	[20]

References

• [1] miR-135b coordinates progression of ErbB2-driven mammary carcinomas through suppression of MID1 and MTCH2.Am J Pathol. 2013 Jun;182(6):2058-70. doi: 10.1016/j.ajpath.2013.02.046. Epub 2013 Apr 23.
• [2] Loss of forebrain MTCH2 decreases mitochondria motility and calcium handling and impairs hippocampal-dependent cognitive functions.Sci Rep. 2017 Mar 9;7:44401. doi: 10.1038/srep44401.
• [3] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [4] Obesity genotype score and cardiovascular risk in women with type 2 diabetes mellitus.Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):327-32. doi: 10.1161/ATVBAHA.109.196196. Epub 2009 Nov 12.
• [5] Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity.Cell Rep. 2016 Feb 23;14(7):1602-1610. doi: 10.1016/j.celrep.2016.01.046. Epub 2016 Feb 11.
• [6] Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population.J Hum Genet. 2009 Dec;54(12):727-31. doi: 10.1038/jhg.2009.106. Epub 2009 Oct 23.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] 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.
• [14] 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.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] 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.
• [18] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [19] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [20] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.