Details of Drug Off-Target (DOT)

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

• DOT Name: Mitochondrial transcription rescue factor 1 (MTRES1)
• Gene Name: MTRES1
• UniProt ID: MRES1_HUMAN
• PDB ID: 7A5H
• Sequence:
  MAMASVKLLAGVLRKPDAWIGLWGVLRGTPSSYKLCTSWNRYLYFSSTKLRAPNYKTLFY
  NIFSLRLPGLLLSPECIFPFSVRLKSNIRSTKSTKKSLQKVDEEDSDEESHHDEMSEQEE
  ELEDDPTVVKNYKDLEKAVQSFRYDVVLKTGLDIGRNKVEDAFYKGELRLNEEKLWKKSR
  TVKVGDTLDLLIGEDKEAGTETVMRILLKKVFEEKTESEKYRVVLRRWKSLKLPKKRMSK
• Function: Mitochondrial RNA-binding protein involved in mitochondrial transcription regulation. Functions as a protective factor to maintain proper mitochondrial RNA level during stress. Acts at the transcription level and its protective function depends on its RNA binding ability. Part of a mitoribosome-associated quality control pathway that prevents aberrant translation by responding to interruptions during elongation. As heterodimer with MTRF, ejects the unfinished nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for MTRES1 and MTRF during mitoribosome rescue.

Molecular Interaction Atlas (MIA) of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Mitochondrial transcription rescue factor 1 (MTRES1).	[1]

8 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 Mitochondrial transcription rescue factor 1 (MTRES1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitochondrial transcription rescue factor 1 (MTRES1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial transcription rescue factor 1 (MTRES1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial transcription rescue factor 1 (MTRES1).	[5]
Pantothenic acid	DM091H2	Approved	Pantothenic acid increases the expression of Mitochondrial transcription rescue factor 1 (MTRES1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial transcription rescue factor 1 (MTRES1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mitochondrial transcription rescue factor 1 (MTRES1).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitochondrial transcription rescue factor 1 (MTRES1).	[9]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.