Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPMDV66)

DOT Name Threonine--tRNA ligase 2, cytoplasmic (TARS3)
Synonyms EC 6.1.1.3; Threonyl-tRNA synthetase; ThrRS; Threonyl-tRNA synthetase protein 3
Gene Name TARS3
Related Disease
Idiopathic inflammatory myopathy ( )
Influenza ( )
Visceral leishmaniasis ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
UniProt ID
SYTC2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
6.1.1.3
Pfam ID
PF03129 ; PF02824 ; PF00587 ; PF07973
Sequence
MAAEALAAEAVASRLERQEEDIRWLWSEVERLRDEQLNAPYSCQAEGPCLTREVAQLRAE
NCDLRHRLCSLRLCLAEERSRQATLESAELEAAQEAGAQPPPSQSQDKDMKKKKMKESEA
DSEVKHQPIFIKERLKLFEILKKDHQLLLAIYGKKGDTSNIITVRVADGQTVQGEVWKTT
PYQVAAEISQELAESTVIAKVNGELWDLDRPLEGDSSLELLTFDNEEAQAVYWHSSAHIL
GEAMELYYGGHLCYGPPIENGFYYDMFIEDRAVSSTELSALENICKAIIKEKQPFERLEV
SKEILLEMFKYNKFKCRILNEKVNTATTTVYRCGPLIDLCKGPHVRHTGKIKTIKIFKNS
STYWEGNPEMETLQRIYGISFPDNKMMRDWEKFQEEAKNRDHRKIGKEQELFFFHDLSPG
SCFFLPRGAFIYNTLTDFIREEYHKRDFTEVLSPNMYNSKLWEASGHWQHYSENMFTFEI
EKDTFALKPMNCPGHCLMFAHRPRSWREMPIRFADFGVLHRNELSGTLSGLTRVRRFQQD
DAHIFCTVEQIEEEIKGCLQFLQSVYSTFGFSFQLNLSTRPENFLGEIEMWNEAEKQLQN
SLMDFGEPWKMNPGDGAFYGPKIDIKIKDAIGRYHQCATIQLDFQLPIRFNLTYVSKDGD
DKKRPVIIHRAILGSVERMIAILSENYGGKWPFWLSPRQVMVIPVGPTCEKYALQVSSEF
FEEGFMADVDLDHSCTLNKKIRNAQLAQYNFILVVGEKEKIDNAVNVRTRDNKIHGEILV
TSAIDKLKNLRKTRTLNAEEAF
Function
Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage.
KEGG Pathway
Aminoacyl-tR. biosynthesis (hsa00970 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Idiopathic inflammatory myopathy DISGB1BZ Strong Biomarker [1]
Influenza DIS3PNU3 Strong Genetic Variation [2]
Visceral leishmaniasis DISTKEYK Strong Biomarker [3]
Epithelial ovarian cancer DIS56MH2 Disputed Altered Expression [4]
Ovarian cancer DISZJHAP Disputed Altered Expression [4]
Ovarian neoplasm DISEAFTY Disputed Altered Expression [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Threonine--tRNA ligase 2, cytoplasmic (TARS3). [5]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Threonine--tRNA ligase 2, cytoplasmic (TARS3). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Threonine--tRNA ligase 2, cytoplasmic (TARS3). [7]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Threonine--tRNA ligase 2, cytoplasmic (TARS3). [9]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Threonine--tRNA ligase 2, cytoplasmic (TARS3). [11]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Threonine--tRNA ligase 2, cytoplasmic (TARS3). [12]
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⏷ Show the Full List of 6 Drug(s)
2 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 Threonine--tRNA ligase 2, cytoplasmic (TARS3). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Threonine--tRNA ligase 2, cytoplasmic (TARS3). [10]
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References

1 Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies.Medicine (Baltimore). 2006 Mar;85(2):111-127. doi: 10.1097/01.md.0000217525.82287.eb.
2 On the nature and use of randomly amplified DNA from Staphylococcus aureus.J Clin Microbiol. 1996 Nov;34(11):2770-7. doi: 10.1128/jcm.34.11.2770-2777.1996.
3 Genetic manipulation of Leishmania donovani threonyl tRNA synthetase facilitates its exploration as a potential therapeutic target.PLoS Negl Trop Dis. 2018 Jun 13;12(6):e0006575. doi: 10.1371/journal.pntd.0006575. eCollection 2018 Jun.
4 Threonyl-tRNA synthetase overexpression correlates with angiogenic markers and progression of human ovarian cancer.BMC Cancer. 2014 Aug 27;14:620. doi: 10.1186/1471-2407-14-620.
5 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
6 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.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 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.
9 BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
10 Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
11 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
12 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.