Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYAOD1Q)

DOT Name	tRNA N(3)-methylcytidine methyltransferase METTL6 (METTL6)
Synonyms	EC 2.1.1.-; Methyltransferase-like protein 6; hMETTL6
Gene Name	METTL6
Related Disease	Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( )
UniProt ID	METL6_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7EZG; 7F1E
EC Number	2.1.1.-
Pfam ID	PF08242
Sequence	MASLQRKGLQARILTSEEEEKLKRDQTLVSDFKQQKLEQEAQKNWDLFYKRNSTNFFKDR HWTTREFEELRSCREFEDQKLTMLEAGCGVGNCLFPLLEEDPNIFAYACDFSPRAIEYVK QNPLYDTERCKVFQCDLTKDDLLDHVPPESVDVVMLIFVLSAVHPDKMHLVLQNIYKVLK PGKSVLFRDYGLYDHAMLRFKASSKLGENFYVRQDGTRSYFFTDDFLAQLFMDTGYEEVV NEYVFRETVNKKEGLCVPRVFLQSKFLKPPKNPSPVVLGLDPKS
Function	S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Ser), including tRNA(Ser)(UGA) and tRNA(Ser)(GCU). Interaction with SARS1/SerRS is required for N(3)-methylcytidine methylation.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	tRNA N(3)-methylcytidine methyltransferase METTL6 (METTL6) increases the response to substance of Cisplatin.	[6]
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4 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 tRNA N(3)-methylcytidine methyltransferase METTL6 (METTL6).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of tRNA N(3)-methylcytidine methyltransferase METTL6 (METTL6).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of tRNA N(3)-methylcytidine methyltransferase METTL6 (METTL6).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of tRNA N(3)-methylcytidine methyltransferase METTL6 (METTL6).	[5]
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References

1	An integrated genomics approach identifies drivers of proliferation in luminal-subtype human breast cancer.Nat Genet. 2014 Oct;46(10):1051-9. doi: 10.1038/ng.3073. Epub 2014 Aug 24.
2	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3	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.
4	The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
5	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
6	Genetic variation predicting cisplatin cytotoxicity associated with overall survival in lung cancer patients receiving platinum-based chemotherapy. Clin Cancer Res. 2011 Sep 1;17(17):5801-11. doi: 10.1158/1078-0432.CCR-11-1133. Epub 2011 Jul 20.