Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1OIVJL)

• DOT Name: Methionyl-tRNA formyltransferase, mitochondrial (MTFMT)
• Synonyms: MtFMT; EC 2.1.2.9
• Gene Name: MTFMT
• Related Disease:
  Leigh syndrome
  Parkinson disease
  Advanced cancer
  Cardiomyopathy
  Combined oxidative phosphorylation defect type 15
  Constipation
  Crohn disease
  Hepatic encephalopathy
  Liver cirrhosis
  Non-small-cell lung cancer
  Pouchitis
  Prostate cancer
  Prostate carcinoma
  Rhegmatogenous retinal detachment
  Ulcerative colitis
  Central diabetes insipidus
  Chronic renal failure
  End-stage renal disease
  Lung cancer
  Lung carcinoma
  Moyamoya disease
  Neoplasm
  Obsolete Leigh syndrome with leukodystrophy
  Asthma
  Attention deficit hyperactivity disorder
  Colitis
  Graft-versus-host disease
  Malignant neoplasm
  Mitochondrial encephalomyopathy
  Nasopharyngeal carcinoma
  Neurodegenerative syndrome due to cerebral folate transport deficiency
• UniProt ID: FMT_HUMAN
• EC Number: 2.1.2.9
• Pfam ID: PF02911 ; PF00551
• Sequence:
  MRVLVRRCWGPPLAHGARRGRPSPQWRALARLGWEDCRDSRVREKPPWRVLFFGTDQFAR
  EALRALHAARENKEEELIDKLEVVTMPSPSPKGLPVKQYAVQSQLPVYEWPDVGSGEYDV
  GVVASFGRLLNEALILKFPYGILNVHPSCLPRWRGPAPVIHTVLHGDTVTGVTIMQIRPK
  RFDVGPILKQETVPVPPKSTAKELEAVLSRLGANMLISVLKNLPESLSNGRQQPMEGATY
  APKISAGTSCIKWEEQTSEQIFRLYRAIGNIIPLQTLWMANTIKLLDLVEVNSSVLADPK
  LTGQALIPGSVIYHKQSQILLVYCKDGWIGVRSVMLKKSLTATDFYNGYLHPWYQKNSQA
  QPSQCRFQTLRLPTKKKQKKTVAMQQCIE
• Function: Methionyl-tRNA formyltransferase that formylates methionyl-tRNA in mitochondria and is crucial for translation initiation.
• KEGG Pathway:
  One carbon pool by folate (hsa00670)
  Aminoacyl-tR. biosynthesis (hsa00970)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leigh syndrome	DISWQU45	Definitive	Autosomal recessive	[1]
Parkinson disease	DISQVHKL	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[4]
Combined oxidative phosphorylation defect type 15	DIS9GQJK	Strong	Autosomal recessive	[5]
Constipation	DISRQXWI	Strong	Biomarker	[6]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[7]
Hepatic encephalopathy	DISEAKAN	Strong	Biomarker	[8]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Pouchitis	DISE28DD	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Rhegmatogenous retinal detachment	DISLE27J	Strong	Biomarker	[12]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[13]
Central diabetes insipidus	DISJ4P9O	moderate	Biomarker	[14]
Chronic renal failure	DISGG7K6	moderate	Genetic Variation	[15]
End-stage renal disease	DISXA7GG	moderate	Genetic Variation	[15]
Lung cancer	DISCM4YA	moderate	Biomarker	[16]
Lung carcinoma	DISTR26C	moderate	Biomarker	[16]
Moyamoya disease	DISO62CA	moderate	Genetic Variation	[15]
Neoplasm	DISZKGEW	moderate	Biomarker	[16]
Obsolete Leigh syndrome with leukodystrophy	DISABU9D	Supportive	Autosomal recessive	[17]
Asthma	DISW9QNS	Limited	Biomarker	[18]
Attention deficit hyperactivity disorder	DISL8MX9	Limited	CausalMutation	[19]
Colitis	DISAF7DD	Limited	Biomarker	[3]
Graft-versus-host disease	DIS0QADF	Limited	Biomarker	[3]
Malignant neoplasm	DISS6SNG	Limited	Biomarker	[3]
Mitochondrial encephalomyopathy	DISA6PTN	Limited	CausalMutation	[19]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[20]
Neurodegenerative syndrome due to cerebral folate transport deficiency	DISGEHPQ	Limited	CausalMutation	[19]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	Methionyl-tRNA formyltransferase, mitochondrial (MTFMT) decreases the response to substance of Josamycin.	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Methionyl-tRNA formyltransferase, mitochondrial (MTFMT).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Methionyl-tRNA formyltransferase, mitochondrial (MTFMT).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Methionyl-tRNA formyltransferase, mitochondrial (MTFMT).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Methionyl-tRNA formyltransferase, mitochondrial (MTFMT).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Methionyl-tRNA formyltransferase, mitochondrial (MTFMT).	[25]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Methionyl-tRNA formyltransferase, mitochondrial (MTFMT).	[26]

References

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• [2] Comparative assessment of 6-[(18) F]fluoro-L-m-tyrosine and 6-[(18) F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model.J Neurochem. 2017 May;141(4):626-635. doi: 10.1111/jnc.14016. Epub 2017 Apr 12.
• [3] Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients.EBioMedicine. 2019 Jun;44:730-740. doi: 10.1016/j.ebiom.2019.03.070. Epub 2019 Mar 30.
• [4] Identification and functional characterization of a novel MTFMT mutation associated with selective vulnerability of the visual pathway and a mild neurological phenotype.Neurogenetics. 2017 Apr;18(2):97-103. doi: 10.1007/s10048-016-0506-0. Epub 2017 Jan 5.
• [5] Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation. Cell Metab. 2011 Sep 7;14(3):428-34. doi: 10.1016/j.cmet.2011.07.010.
• [6] Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria.Haematologica. 2019 Aug;104(8):1682-1688. doi: 10.3324/haematol.2018.198549. Epub 2019 Feb 7.
• [7] Paediatric inflammatory bowel disease: review with a focus on practice in low- to middle-income countries.Paediatr Int Child Health. 2019 Feb;39(1):48-58. doi: 10.1080/20469047.2019.1575056.
• [8] Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis.JCI Insight. 2019 Dec 19;4(24):e133410. doi: 10.1172/jci.insight.133410.
• [9] Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer.Neoplasia. 2017 Jan;19(1):8-16. doi: 10.1016/j.neo.2016.11.009. Epub 2016 Dec 7.
• [10] Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.J Crohns Colitis. 2017 Oct 1;11(10):1180-1199. doi: 10.1093/ecco-jcc/jjx063.
• [11] The role of the intravascular microenvironment in spontaneous metastasis development.Int J Cancer. 2010 Jun 1;126(11):2534-41. doi: 10.1002/ijc.24979.
• [12] Vascular changes after vitrectomy for rhegmatogenous retinal detachment: optical coherence tomography angiography study.Acta Ophthalmol. 2020 Aug;98(5):e563-e569. doi: 10.1111/aos.14315. Epub 2019 Nov 26.
• [13] Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study).J Gastroenterol Hepatol. 2020 Mar;35(3):418-424. doi: 10.1111/jgh.14829. Epub 2019 Sep 1.
• [14] Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: A case report.Pediatr Transplant. 2020 Feb;24(1):e13598. doi: 10.1111/petr.13598. Epub 2019 Oct 16.
• [15] Challenges managing end-stage renal disease and kidney transplantation in a child with MTFMT mutation and moyamoya disease.Pediatr Transplant. 2016 Nov;20(7):1000-1003. doi: 10.1111/petr.12758. Epub 2016 Jul 8.
• [16] Early recognition of lung cancer by integrin targeted imaging in K-ras mouse model.Int J Cancer. 2015 Sep 1;137(5):1107-18. doi: 10.1002/ijc.29372. Epub 2015 Jan 14.
• [17] Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing. J Med Genet. 2012 Apr;49(4):277-83. doi: 10.1136/jmedgenet-2012-100846.
• [18] Fibroblast gene expression following asthmatic bronchial epithelial cell conditioning correlates with epithelial donor lung function and exacerbation history.Sci Rep. 2018 Oct 25;8(1):15768. doi: 10.1038/s41598-018-34021-6.
• [19] Phenotypic spectrum of eleven patients and five novel MTFMT mutations identified by exome sequencing and candidate gene screening.Mol Genet Metab. 2014 Mar;111(3):342-352. doi: 10.1016/j.ymgme.2013.12.010. Epub 2013 Dec 25.
• [20] In vivo three-dimensional evaluation of tumour hypoxia in nasopharyngeal carcinomas using FMT-CT and MSOT.Eur J Nucl Med Mol Imaging. 2020 May;47(5):1027-1038. doi: 10.1007/s00259-019-04526-x. Epub 2019 Nov 8.
• [21] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [22] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [26] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [27] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.