Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRYA1HU)

• DOT Name: rRNA methyltransferase 2, mitochondrial (MRM2)
• Synonyms: EC 2.1.1.-; 16S rRNA (uridine(1369)-2'-O)-methyltransferase; 16S rRNA 2'-O-methyltransferase; Protein ftsJ homolog 2
• Gene Name: MRM2
• Related Disease: Mitochondrial DNA depletion syndrome 17
• UniProt ID: MRM2_HUMAN
• PDB ID: 2NYU; 7O9K; 7O9M; 7ODS
• EC Number: 2.1.1.-
• Pfam ID: PF01728
• Sequence:
  MAGYLKLVCVSFQRQGFHTVGSRCKNRTGAEHLWLTRHLRDPFVKAAKVESYRCRSAFKL
  LEVNERHQILRPGLRVLDCGAAPGAWSQVAVQKVNAAGTDPSSPVGFVLGVDLLHIFPLE
  GATFLCPADVTDPRTSQRILEVLPGRRADVILSDMAPNATGFRDLDHDRLISLCLTLLSV
  TPDILQPGGTFLCKTWAGSQSRRLQRRLTEEFQNVRIIKPEASRKESSEVYFLATQYHGR
  KGTVKQ
• Function: S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyzes the formation of 2'-O-methyluridine at position 1369 (Um1369) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase domain of the mtLSU rRNA.
• Tissue Specificity: Widely expressed, with highest expression in muscle, placenta, and heart.
• Reactome Pathway: rRNA modification in the mitochondrion (R-HSA-6793080)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial DNA depletion syndrome 17	DISE8EKL	Limited	Autosomal recessive	[1]

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 rRNA methyltransferase 2, mitochondrial (MRM2).	[2]

13 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 rRNA methyltransferase 2, mitochondrial (MRM2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[7]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[5]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[5]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[5]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[5]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[9]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of rRNA methyltransferase 2, mitochondrial (MRM2).	[10]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [6] 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.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.