Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0F9ADF)

• DOT Name: Mitochondrial carrier homolog 1 (MTCH1)
• Synonyms: Presenilin-associated protein
• Gene Name: MTCH1
• UniProt ID: MTCH1_HUMAN
• Pfam ID: PF00153
• Sequence:
  MGASDPEVAPWARGGAAGMAGAGAGAGARGGAAAGVEARARDPPPAHRAHPRHPRPAAQP
  SARRMDGGSGGLGSGDNAPTTEALFVALGAGVTALSHPLLYVKLLIQVGHEPMPPTLGTN
  VLGRKVLYLPSFFTYAKYIVQVDGKIGLFRGLSPRLMSNALSTVTRGSMKKVFPPDEIEQ
  VSNKDDMKTSLKKVVKETSYEMMMQCVSRMLAHPLHVISMRCMVQFVGREAKYSGVLSSI
  GKIFKEEGLLGFFVGLIPHLLGDVVFLWGCNLLAHFINAYLVDDSVSDTPGGLGNDQNPG
  SQFSQALAIRSYTKFVMGIAVSMLTYPFLLVGDLMAVNNCGLQAGLPPYSPVFKSWIHCW
  KYLSVQGQLFRGSSLLFRRVSSGSCFALE
• 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. May play a role in apoptosis.
• Tissue Specificity: Widely expressed with a predominant expression in brain.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial carrier homolog 1 (MTCH1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitochondrial carrier homolog 1 (MTCH1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Mitochondrial carrier homolog 1 (MTCH1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial carrier homolog 1 (MTCH1).	[4]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of Mitochondrial carrier homolog 1 (MTCH1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial carrier homolog 1 (MTCH1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitochondrial carrier homolog 1 (MTCH1).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Mitochondrial carrier homolog 1 (MTCH1).	[9]

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 increases the methylation of Mitochondrial carrier homolog 1 (MTCH1).	[6]

References

• [1] 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.
• [2] 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.
• [3] Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells. Br J Pharmacol. 2013 May;169(1):167-78.
• [4] 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.
• [5] 4-HPR modulates gene expression in ovarian cells. Int J Cancer. 2006 Sep 1;119(5):1005-13. doi: 10.1002/ijc.21797.
• [6] 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.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.