Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVX5QEO)

• DOT Name: Peptide chain release factor 1-like, mitochondrial (MTRF1L)
• Synonyms: Mitochondrial translational release factor 1-like; mtRF1a
• Gene Name: MTRF1L
• UniProt ID: RF1ML_HUMAN
• PDB ID: 7NQH
• Pfam ID: PF03462 ; PF00472
• Sequence:
  MRSRVLWGAARWLWPRRAVGPARRPLSSGSPPLEELFTRGGPLRTFLERQAGSEAHLKVR
  RPELLAVIKLLNEKERELRETEHLLHDENEDLRKLAENEITLCQKEITQLKHQIILLLVP
  SEETDENDLILEVTAGVGGQEAMLFTSEIFDMYQQYAAFKRWHFETLEYFPSELGGLRHA
  SASIGGSEAYRHMKFEGGVHRVQRVPKTEKQGRVHTSTMTVAILPQPTEINLVINPKDLR
  IDTKRASGAGGQHVNTTDSAVRIVHLPTGVVSECQQERSQLKNKELAMTKLRAKLYSMHL
  EEEINKRQNARKIQIGSKGRSEKIRTYNFPQNRVTDHRINKTLHDLETFMQGDYLLDELV
  QSLKEYADYESLVEIISQKV
• Function: Mitochondrial peptide chain release factor that directs the termination of translation in response to the peptide chain termination codons UAA and UAG.
• Tissue Specificity: Expressed in skeletal muscle (at protein level).
• Reactome Pathway: Mitochondrial translation termination (R-HSA-5419276)

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 decreases the methylation of Peptide chain release factor 1-like, mitochondrial (MTRF1L).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Peptide chain release factor 1-like, mitochondrial (MTRF1L).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peptide chain release factor 1-like, mitochondrial (MTRF1L).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Peptide chain release factor 1-like, mitochondrial (MTRF1L).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Peptide chain release factor 1-like, mitochondrial (MTRF1L).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peptide chain release factor 1-like, mitochondrial (MTRF1L).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peptide chain release factor 1-like, mitochondrial (MTRF1L).	[7]

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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.