Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWXKTL0)

DOT Name Valine--tRNA ligase, mitochondrial
Synonyms EC 6.1.1.9; Valyl-tRNA synthetase; ValRS; Valyl-tRNA synthetase-like
Gene Name VARS2
Related Disease
Mitochondrial disease ( )
Combined oxidative phosphorylation defect type 20 ( )
UniProt ID
SYVM_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
6.1.1.9
Pfam ID
PF08264 ; PF00133
Sequence
MPHLPLASFRPPFWGLRHSRGLPRFHSVSTQSEPHGSPISRRNREAKQKRLREKQATLEA
EIAGESKSPAESIKAWRPKELVLYEIPTKPGEKKDVSGPLPPAYSPRYVEAAWYPWWVRE
GFFKPEYQARLPQATGETFSMCIPPPNVTGSLHIGHALTVAIQDALVRWHRMRGDQVLWV
PGSDHAGIATQAVVEKQLWKERGVRRHELSREAFLREVWQWKEAKGGEICEQLRALGASL
DWDRECFTMDVGSSVAVTEAFVRLYKAGLLYRNHQLVNWSCALRSAISDIEVENRPLPGH
TQLRLPGCPTPVSFGLLFSVAFPVDGEPDAEVVVGTTRPETLPGDVAVAVHPDDSRYTHL
HGRQLRHPLMGQPLPLITDYAVQPHVGTGAVKVTPAHSPADAEMGARHGLSPLNVIAEDG
TMTSLCGDWLQGLHRFVAREKIMSVLSEWGLFRGLQNHPMVLPICSRSGDVIEYLLKNQW
FVRCQEMGARAAKAVESGALELSPSFHQKNWQHWFSHIGDWCVSRQLWWGHQIPAYLVVE
DHAQGEEDCWVVGRSEAEAREVAAELTGRPGAELTLERDPDVLDTWFSSALFPFSALGWP
QETPDLARFYPLSLLETGSDLLLFWVGRMVMLGTQLTGQLPFSKVLLHPMVRDRQGRKMS
KSLGNVLDPRDIISGVEMQVLQEKLRSGNLDPAELAIVAAAQKKDFPHGIPECGTDALRF
TLCSHGVQAGDLHLSVSEVQSCRHFCNKIWNALRFILNALGEKFVPQPAEELSPSSPMDA
WILSRLALAAQECERGFLTRELSLVTHALHHFWLHNLCDVYLEAVKPVLWHSPRPLGPPQ
VLFSCADLGLRLLAPLMPFLAEELWQRLPPRPGCPPAPSISVAPYPSACSLEHWRQPELE
RRFSRVQEVVQVLRALRATYQLTKARPRVLLQSSEPGDQGLFEAFLEPLGTLGYCGAVGL
LPPGAAAPSGWAQAPLSDTAQVYMELQGLVDPQIQLPLLAARRYKLQKQLDSLTARTPSE
GEAGTQRQQKLSSLQLELSKLDKAASHLRQLMDEPPAPGSPEL
Function Catalyzes the attachment of valine to tRNA(Val) in a two-step reaction: valine is first activated by ATP to form Val-AMP and then transferred to the acceptor end of tRNA(Val).
KEGG Pathway
Aminoacyl-tR. biosynthesis (hsa00970 )
Reactome Pathway
Mitochondrial tRNA aminoacylation (R-HSA-379726 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Mitochondrial disease DISKAHA3 Definitive Autosomal recessive [1]
Combined oxidative phosphorylation defect type 20 DISVDTZV Strong Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 Valine--tRNA ligase, mitochondrial. [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Valine--tRNA ligase, mitochondrial. [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Valine--tRNA ligase, mitochondrial. [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Valine--tRNA ligase, mitochondrial. [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Valine--tRNA ligase, mitochondrial. [7]
Selenium DM25CGV Approved Selenium increases the expression of Valine--tRNA ligase, mitochondrial. [9]
Menadione DMSJDTY Approved Menadione affects the expression of Valine--tRNA ligase, mitochondrial. [10]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Valine--tRNA ligase, mitochondrial. [9]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Valine--tRNA ligase, mitochondrial. [7]
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⏷ Show the Full List of 9 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Valine--tRNA ligase, mitochondrial. [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Valine--tRNA ligase, mitochondrial. [11]
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References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies. Hum Mutat. 2014 Aug;35(8):983-9. doi: 10.1002/humu.22590. Epub 2014 Jun 24.
3 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.
4 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.
5 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.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
8 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
9 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.
10 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
11 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.