Details of Drug Off-Target (DOT)

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

• DOT Name: Transcription termination factor 2, mitochondrial (MTERF2)
• Synonyms: Mitochondrial transcription termination factor 2; mTERF2; Mitochondrial transcription termination factor-like protein; mTERF-like; mTERFL; mTERF domain-containing protein 3, mitochondrial
• Gene Name: MTERF2
• Related Disease: Non-small-cell lung cancer
• UniProt ID: MTEF2_HUMAN
• Pfam ID: PF02536
• Sequence:
  MLWKLLLRSQSCRLCSFRKMRSPPKYRPFLACFTYTTDKQSSKENTRTVEKLYKCSVDIR
  KIRRLKGWVLLEDETYVEEIANILQELGADETAVASILERCPEAIVCSPTAVNTQRKLWQ
  LVCKNEEELIKLIEQFPESFFTIKDQENQKLNVQFFQELGLKNVVISRLLTAAPNVFHNP
  VEKNKQMVRILQESYLDVGGSEANMKVWLLKLLSQNPFILLNSPTAIKETLEFLQEQGFT
  SFEILQLLSKLKGFLFQLCPRSIQNSISFSKNAFKCTDHDLKQLVLKCPALLYYSVPVLE
  ERMQGLLREGISIAQIRETPMVLELTPQIVQYRIRKLNSSGYRIKDGHLANLNGSKKEFE
  ANFGKIQAKKVRPLFNPVAPLNVEE
• Function: Binds mitochondrial DNA and plays a role in the regulation of transcription of mitochondrial mRNA and rRNA species.
• Tissue Specificity: Expressed in skeletal muscle, heart, liver and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]

8 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 Transcription termination factor 2, mitochondrial (MTERF2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription termination factor 2, mitochondrial (MTERF2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription termination factor 2, mitochondrial (MTERF2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription termination factor 2, mitochondrial (MTERF2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription termination factor 2, mitochondrial (MTERF2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription termination factor 2, mitochondrial (MTERF2).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transcription termination factor 2, mitochondrial (MTERF2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription termination factor 2, mitochondrial (MTERF2).	[10]

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 decreases the methylation of Transcription termination factor 2, mitochondrial (MTERF2).	[8]

References

• [1] Prognostic roles of mitochondrial transcription termination factors in non-small cell lung cancer.Oncol Lett. 2019 Oct;18(4):3453-3462. doi: 10.3892/ol.2019.10680. Epub 2019 Jul 29.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [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] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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.