Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3PK0Q0)

• DOT Name: rRNA methyltransferase 1, mitochondrial (MRM1)
• Synonyms: EC 2.1.1.-; 16S rRNA (guanosine(1145)-2'-O)-methyltransferase; 16S rRNA 2'-O-methyltransferase
• Gene Name: MRM1
• UniProt ID: MRM1_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF00588 ; PF08032
• Sequence:
  MALLSTVRGATWGRLVTRHFSHAARHGERPGGEELSRLLLDDLVPTSRLELLFGMTPCLL
  ALQAARRSVARLLLQAGKAGLQGKRAELLRMAEARDIPVLRPRRQKLDTMCRYQVHQGVC
  MEVSPLRPRPWREAGEASPGDDPQQLWLVLDGIQDPRNFGAVLRSAHFLGVDKVITSRRN
  SCPLTPVVSKSSAGAMEVMDVFSTDDLTGFLQTKAQQGWLVAGTVGCPSTEDPQSSEIPI
  MSCLEFLWERPTLLVLGNEGSGLSQEVQASCQLLLTILPRRQLPPGLESLNVSVAAGILL
  HSICSQRKGFPTEGERRQLLQDPQEPSARSEGLSMAQHPGLSSGPEKERQNEG
• Function: S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyzes the formation of 2'-O-methylguanosine at position 1145 (Gm1145) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase domain of the mtLSU rRNA.
• Reactome Pathway: rRNA modification in the mitochondrion (R-HSA-6793080)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of rRNA methyltransferase 1, mitochondrial (MRM1).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of rRNA methyltransferase 1, mitochondrial (MRM1).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of rRNA methyltransferase 1, mitochondrial (MRM1).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of rRNA methyltransferase 1, mitochondrial (MRM1).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of rRNA methyltransferase 1, mitochondrial (MRM1).	[6]

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 increases the methylation of rRNA methyltransferase 1, mitochondrial (MRM1).	[4]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] 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.
• [5] 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.
• [6] 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.