Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVE8W7X)

• DOT Name: Transcription termination factor 3, mitochondrial (MTERF3)
• Synonyms: Mitochondrial transcription termination factor 3; mTERF3; mTERF domain-containing protein 1, mitochondrial
• Gene Name: MTERF3
• UniProt ID: MTEF3_HUMAN
• PDB ID: 3M66
• Pfam ID: PF02536
• Sequence:
  MALSAQQIPRWFNSVKLRSLINAAQLTKRFTRPARTLLHGFSAQPQISSDNCFLQWGFKT
  YRTSSLWNSSQSTSSSSQENNSAQSSLLPSMNEQSQKTQNISSFDSELFLEELDELPPLS
  PMQPISEEEAIQIIADPPLPPASFTLRDYVDHSETLQKLVLLGVDLSKIEKHPEAANLLL
  RLDFEKDIKQMLLFLKDVGIEDNQLGAFLTKNHAIFSEDLENLKTRVAYLHSKNFSKADV
  AQMVRKAPFLLNFSVERLDNRLGFFQKELELSVKKTRDLVVRLPRLLTGSLEPVKENMKV
  YRLELGFKHNEIQHMITRIPKMLTANKMKLTETFDFVHNVMSIPHHIIVKFPQVFNTRLF
  KVKERHLFLTYLGRAQYDPAKPNYISLDKLVSIPDEIFCEEIAKASVQDFEKFLKTL
• Function: Binds promoter DNA and regulates initiation of transcription. Required for normal mitochondrial transcription and translation, and for normal assembly of mitochondrial respiratory complexes. Required for normal mitochondrial function. Maintains 16S rRNA levels and functions in mitochondrial ribosome assembly by regulating the biogenesis of the 39S ribosomal subunit.
• Tissue Specificity: Highly expressed in heart, liver, kidney and testis. Detected at lower levels in brain, spleen and lung.
• Reactome Pathway: PINK1-PRKN Mediated Mitophagy (R-HSA-5205685)

Molecular Interaction Atlas (MIA) of This DOT

15 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 3, mitochondrial (MTERF3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[13]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[14]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Transcription termination factor 3, mitochondrial (MTERF3).	[15]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [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] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [15] MTERF3 contributes to MPP+-induced mitochondrial dysfunction in SH-SY5Y cells. Acta Biochim Biophys Sin (Shanghai). 2022 Aug 25;54(8):1113-1121. doi: 10.3724/abbs.2022098.