Details of Drug Off-Target (DOT)

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

DOT Name tRNA (TRMT61B)
Synonyms adenine(58)-N(1))-methyltransferase, mitochondrial (EC 2.1.1.220; mRNA methyladenosine-N(1)-methyltransferase; EC 2.1.1.-
Gene Name TRMT61B
UniProt ID
TR61B_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2B25
EC Number
2.1.1.-; 2.1.1.220
Pfam ID
PF08704
Sequence
MLMAWCRGPVLLCLRQGLGTNSFLHGLGQEPFEGARSLCCRSSPRDLRDGEREHEAAQRK
APGAESCPSLPLSISDIGTGCLSSLENLRLPTLREESSPRELEDSSGDQGRCGPTHQGSE
DPSMLSQAQSATEVEERHVSPSCSTSRERPFQAGELILAETGEGETKFKKLFRLNNFGLL
NSNWGAVPFGKIVGKFPGQILRSSFGKQYMLRRPALEDYVVLMKRGTAITFPKDINMILS
MMDINPGDTVLEAGSGSGGMSLFLSKAVGSQGRVISFEVRKDHHDLAKKNYKHWRDSWKL
SHVEEWPDNVDFIHKDISGATEDIKSLTFDAVALDMLNPHVTLPVFYPHLKHGGVCAVYV
VNITQVIELLDGIRTCELALSCEKISEVIVRDWLVCLAKQKNGILAQKVESKINTDVQLD
SQEKIGVKGELFQEDDHEESHSDFPYGSFPYVARPVHWQPGHTAFLVKLRKVKPQLN
Function
Methyltransferase that catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in various tRNAs in mitochondrion, including tRNA(Leu) (deciphering codons UUA or UUG), tRNA(Lys) and tRNA(Ser) (deciphering codons UCA, UCU, UCG or UCC). Catalyzes the formation of 1-methyladenosine at position 947 of mitochondrial 16S ribosomal RNA and this modification is most likely important for mitoribosomal structure and function. In addition to tRNA N(1)-methyltransferase activity, also acts as a mRNA N(1)-methyltransferase by mediating methylation of adenosine residues at the N(1) position of MT-ND5 mRNA, leading to interfere with mitochondrial translation.
Reactome Pathway
tRNA modification in the mitochondrion (R-HSA-6787450 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of tRNA (TRMT61B). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of tRNA (TRMT61B). [2]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of tRNA (TRMT61B). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of tRNA (TRMT61B). [4]
Quercetin DM3NC4M Approved Quercetin decreases the expression of tRNA (TRMT61B). [5]
Selenium DM25CGV Approved Selenium decreases the expression of tRNA (TRMT61B). [6]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of tRNA (TRMT61B). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of tRNA (TRMT61B). [5]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of tRNA (TRMT61B). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of tRNA (TRMT61B). [9]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of tRNA (TRMT61B). [10]
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⏷ Show the Full List of 11 Drug(s)

References

1 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
2 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
3 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
6 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
7 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
8 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.
9 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.
10 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.