Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJDU2UG)

DOT Name Glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial (QRSL1)
Synonyms Glu-AdT subunit A; EC 6.3.5.7; Glutaminyl-tRNA synthase-like protein 1
Gene Name QRSL1
Related Disease
Carcinoma of esophagus ( )
Esophageal cancer ( )
Hypoparathyroidism ( )
Myeloid leukaemia ( )
Neoplasm of esophagus ( )
Acute myelogenous leukaemia ( )
Autism ( )
Autoimmune disease ( )
Barrett esophagus ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Cardiac failure ( )
Colon cancer ( )
Colon carcinoma ( )
Combined oxidative phosphorylation deficiency 40 ( )
Congenital contractural arachnodactyly ( )
Congestive heart failure ( )
Cytomegalovirus infection ( )
Endometriosis ( )
Hepatocellular carcinoma ( )
Hypoparathyroidism-deafness-renal disease syndrome ( )
Inflammatory bowel disease ( )
leukaemia ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Myelodysplastic syndrome ( )
Neoplasm ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Ovarian neoplasm ( )
Promyelocytic leukaemia ( )
Prostate cancer ( )
Prostate carcinoma ( )
Renal cell carcinoma ( )
Trichorhinophalangeal syndrome ( )
Wilms tumor ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Acute lymphocytic leukaemia ( )
Advanced cancer ( )
Arrhythmia ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Hematologic disease ( )
Pancreatic ductal carcinoma ( )
Parkinson disease ( )
Type-1 diabetes ( )
UniProt ID
GATA_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
6.3.5.7
Pfam ID
PF01425
Sequence
MLGRSLREVSAALKQGQITPTELCQKCLSLIKKTKFLNAYITVSEEVALKQAEESEKRYK
NGQSLGDLDGIPIAVKDNFSTSGIETTCASNMLKGYIPPYNATVVQKLLDQGALLMGKTN
LDEFAMGSGSTDGVFGPVKNPWSYSKQYREKRKQNPHSENEDSDWLITGGSSGGSAAAVS
AFTCYAALGSDTGGSTRNPAAHCGLVGFKPSYGLVSRHGLIPLVNSMDVPGILTRCVDDA
AIVLGALAGPDPRDSTTVHEPINKPFMLPSLADVSKLCIGIPKEYLVPELSSEVQSLWSK
AADLFESEGAKVIEVSLPHTSYSIVCYHVLCTSEVASNMARFDGLQYGHRCDIDVSTEAM
YAATRREGFNDVVRGRILSGNFFLLKENYENYFVKAQKVRRLIANDFVNAFNSGVDVLLT
PTTLSEAVPYLEFIKEDNRTRSAQDDIFTQAVNMAGLPAVSIPVALSNQGLPIGLQFIGR
AFCDQQLLTVAKWFEKQVQFPVIQLQELMDDCSAVLENEKLASVSLKQ
Function
Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln).
KEGG Pathway
Aminoacyl-tR. biosynthesis (hsa00970 )
Metabolic pathways (hsa01100 )

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of esophagus DISS6G4D Definitive Posttranslational Modification [1]
Esophageal cancer DISGB2VN Definitive Posttranslational Modification [1]
Hypoparathyroidism DISICS0V Definitive Genetic Variation [2]
Myeloid leukaemia DISMN944 Definitive Biomarker [3]
Neoplasm of esophagus DISOLKAQ Definitive Posttranslational Modification [1]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [4]
Autism DISV4V1Z Strong Biomarker [5]
Autoimmune disease DISORMTM Strong Biomarker [6]
Barrett esophagus DIS416Y7 Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Breast neoplasm DISNGJLM Strong Altered Expression [9]
Carcinoma DISH9F1N Strong Altered Expression [10]
Cardiac failure DISDC067 Strong Genetic Variation [11]
Colon cancer DISVC52G Strong Biomarker [12]
Colon carcinoma DISJYKUO Strong Biomarker [12]
Combined oxidative phosphorylation deficiency 40 DISVK7JB Strong Autosomal recessive [13]
Congenital contractural arachnodactyly DISOM1K7 Strong Altered Expression [14]
Congestive heart failure DIS32MEA Strong Genetic Variation [11]
Cytomegalovirus infection DISCEMGC Strong Biomarker [15]
Endometriosis DISX1AG8 Strong Posttranslational Modification [16]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [17]
Hypoparathyroidism-deafness-renal disease syndrome DISRCBP9 Strong Altered Expression [18]
Inflammatory bowel disease DISGN23E Strong Biomarker [19]
leukaemia DISS7D1V Strong Biomarker [20]
Leukemia DISNAKFL Strong Biomarker [20]
Lung cancer DISCM4YA Strong Genetic Variation [21]
Lung carcinoma DISTR26C Strong Genetic Variation [21]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [22]
Neoplasm DISZKGEW Strong Posttranslational Modification [23]
Neuroblastoma DISVZBI4 Strong Genetic Variation [24]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [25]
Obesity DIS47Y1K Strong Genetic Variation [26]
Ovarian neoplasm DISEAFTY Strong Altered Expression [27]
Promyelocytic leukaemia DISYGG13 Strong Biomarker [28]
Prostate cancer DISF190Y Strong Altered Expression [29]
Prostate carcinoma DISMJPLE Strong Altered Expression [29]
Renal cell carcinoma DISQZ2X8 Strong Genetic Variation [30]
Trichorhinophalangeal syndrome DISO1AEK Strong Genetic Variation [31]
Wilms tumor DISB6T16 Strong Biomarker [32]
Epithelial ovarian cancer DIS56MH2 moderate Altered Expression [27]
Ovarian cancer DISZJHAP moderate Altered Expression [27]
Acute lymphocytic leukaemia DISPX75S Limited Altered Expression [33]
Advanced cancer DISAT1Z9 Limited Biomarker [34]
Arrhythmia DISFF2NI Limited Altered Expression [35]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [36]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [36]
Hematologic disease DIS9XD9A Limited Biomarker [37]
Pancreatic ductal carcinoma DIS26F9Q Limited Biomarker [38]
Parkinson disease DISQVHKL Limited Altered Expression [39]
Type-1 diabetes DIS7HLUB Limited Biomarker [40]
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⏷ Show the Full List of 51 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial (QRSL1). [41]
Marinol DM70IK5 Approved Marinol increases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial (QRSL1). [42]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Glutamyl-tRNA(Gln) amidotransferase subunit A, mitochondrial (QRSL1). [43]
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References

1 Hypermethylation of the GATA gene family in esophageal cancer.Int J Cancer. 2006 Nov 1;119(9):2078-83. doi: 10.1002/ijc.22092.
2 The syndrome of hypoparathyroidism, deafness, and renal anomalies.Endocr Pract. 2013 Nov-Dec;19(6):1035-42. doi: 10.4158/EP13050.RA.
3 COUP-TFII is a modulator of cell-type-specific genetic programs based on genomic localization maps.J Biotechnol. 2019 Aug 10;301:11-17. doi: 10.1016/j.jbiotec.2019.05.305. Epub 2019 May 31.
4 UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs.Nat Genet. 2018 Jun;50(6):883-894. doi: 10.1038/s41588-018-0114-z. Epub 2018 May 7.
5 Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism.Mol Neurobiol. 2017 Aug;54(6):4390-4400. doi: 10.1007/s12035-016-9977-0. Epub 2016 Jun 25.
6 Tcell-derived IFN- downregulates protective group 2 innate lymphoid cells in murine lupus erythematosus.Eur J Immunol. 2018 Aug;48(8):1364-1375. doi: 10.1002/eji.201747303. Epub 2018 May 17.
7 GATA factors in gastrointestinal malignancy.World J Surg. 2011 Aug;35(8):1757-65. doi: 10.1007/s00268-010-0950-1.
8 Comprehensive analysis of the GATA transcription factor gene family in breast carcinoma using gene microarrays, online databases and integrated bioinformatics.Sci Rep. 2019 Mar 14;9(1):4467. doi: 10.1038/s41598-019-40811-3.
9 Protein kinase A-dependent synergism between GATA factors and the nuclear receptor, liver receptor homolog-1, regulates human aromatase (CYP19) PII promoter activity in breast cancer cells.Endocrinology. 2005 Nov;146(11):4905-16. doi: 10.1210/en.2005-0187. Epub 2005 Aug 18.
10 Tricho-rhino-phalangeal syndrome 1 protein functions as a scaffold required for ubiquitin-specific protease 4-directed histone deacetylase 2 de-ubiquitination and tumor growth.Breast Cancer Res. 2018 Aug 2;20(1):83. doi: 10.1186/s13058-018-1018-7.
11 Protein kinase C regulates internal initiation of translation of the GATA-4 mRNA following vasopressin-induced hypertrophy of cardiac myocytes.J Biol Chem. 2007 Mar 30;282(13):9505-9516. doi: 10.1074/jbc.M608874200. Epub 2007 Feb 6.
12 Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes.Proc Natl Acad Sci U S A. 2007 May 8;104(19):8023-8. doi: 10.1073/pnas.0700720104. Epub 2007 Apr 26.
13 A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies. PLoS Genet. 2016 Jan 7;12(1):e1005679. doi: 10.1371/journal.pgen.1005679. eCollection 2016 Jan.
14 The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma.Int J Oncol. 2019 Sep;55(3):657-670. doi: 10.3892/ijo.2019.4837. Epub 2019 Jul 15.
15 GATA2 mutation underlies hemophagocytic lymphohistiocytosis in an adult with primary cytomegalovirus infection.J Infect Chemother. 2020 Feb;26(2):252-256. doi: 10.1016/j.jiac.2019.07.002. Epub 2019 Jul 23.
16 Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis.PLoS Genet. 2014 Mar 6;10(3):e1004158. doi: 10.1371/journal.pgen.1004158. eCollection 2014 Mar.
17 Decreased expression of GATA2 promoted proliferation, migration and invasion of HepG2 in vitro and correlated with poor prognosis of hepatocellular carcinoma.PLoS One. 2014 Jan 30;9(1):e87505. doi: 10.1371/journal.pone.0087505. eCollection 2014.
18 Identification of a novel insertion mutation in GATA3 with HDR syndrome.Clin Exp Nephrol. 2005 Mar;9(1):58-61. doi: 10.1007/s10157-004-0327-6.
19 Microscopic Colitis Evolved Into Inflammatory Bowel Diseases Is Characterized by Increased Th1/Tc1 Cells in Colonic Mucosal Lamina Propria.Dig Dis Sci. 2017 Oct;62(10):2755-2767. doi: 10.1007/s10620-017-4636-5. Epub 2017 Jun 9.
20 GATA4 is highly expressed in childhood acute lymphoblastic leukemia, promotes cell proliferation and inhibits apoptosis by activating BCL2 and MDM2.Mol Med Rep. 2017 Nov;16(5):6290-6298. doi: 10.3892/mmr.2017.7369. Epub 2017 Aug 28.
21 Hypermethylation of the GATA genes in lung cancer.Clin Cancer Res. 2004 Dec 1;10(23):7917-24. doi: 10.1158/1078-0432.CCR-04-1140.
22 Pediatric MDS: GATA screen the germline.Blood. 2016 Mar 17;127(11):1377-8. doi: 10.1182/blood-2016-01-690016.
23 GATA3 and TRPS1 are distinct biomarkers and prognostic factors in breast cancer: database mining for GATA family members in malignancies.Oncotarget. 2017 May 23;8(21):34750-34761. doi: 10.18632/oncotarget.16160.
24 Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism.Nature. 2015 Dec 17;528(7582):418-21. doi: 10.1038/nature15540. Epub 2015 Nov 11.
25 Type 2 diabetes-associated fatty acid binding protein 2 promoter haplotypes are differentially regulated by GATA factors.Hum Mutat. 2008 Jan;29(1):142-9. doi: 10.1002/humu.20618.
26 Association analysis indicates that a variant GATA-binding site in the PIK3CB promoter is a Cis-acting expression quantitative trait locus for this gene and attenuates insulin resistance in obese children.Diabetes. 2008 Feb;57(2):494-502. doi: 10.2337/db07-1273. Epub 2007 Oct 31.
27 Histone modifications silence the GATA transcription factor genes in ovarian cancer.Oncogene. 2006 Aug 31;25(39):5446-61. doi: 10.1038/sj.onc.1209533. Epub 2006 Apr 10.
28 Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein.Blood. 2002 May 1;99(9):3404-10. doi: 10.1182/blood.v99.9.3404.
29 A role for GATA-2 in transition to an aggressive phenotype in prostate cancer through modulation of key androgen-regulated genes.Oncogene. 2009 Oct 29;28(43):3847-56. doi: 10.1038/onc.2009.243. Epub 2009 Aug 17.
30 GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma.Oncol Rep. 2014 Apr;31(4):1523-30. doi: 10.3892/or.2014.3030. Epub 2014 Feb 18.
31 miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to-mesenchymal transition in breast cancer.Sci Signal. 2011 Aug 9;4(186):pt5. doi: 10.1126/scisignal.2002258.
32 GATA-1 and GATA-2 binding to 3' enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines.Leukemia. 2009 Jul;23(7):1270-7. doi: 10.1038/leu.2009.13. Epub 2009 Feb 12.
33 Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells.Int J Hematol. 1997 Apr;65(3):239-49. doi: 10.1016/s0925-5710(96)00553-1.
34 Transcription Factors That Govern Development and Disease: An Achilles Heel in Cancer.Genes (Basel). 2019 Oct 12;10(10):794. doi: 10.3390/genes10100794.
35 Fetal Arrhythmias: Genetic Background and Clinical Implications.Pediatr Cardiol. 2019 Feb;40(2):247-256. doi: 10.1007/s00246-018-2008-3. Epub 2018 Nov 26.
36 Genetic variation associated with circulating monocyte count in the eMERGE Network.Hum Mol Genet. 2013 May 15;22(10):2119-27. doi: 10.1093/hmg/ddt010. Epub 2013 Jan 12.
37 The GATA factor revolution in hematology.Blood. 2017 Apr 13;129(15):2092-2102. doi: 10.1182/blood-2016-09-687871. Epub 2017 Feb 8.
38 GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer.Gut. 2017 Sep;66(9):1665-1676. doi: 10.1136/gutjnl-2015-311256. Epub 2016 Jun 20.
39 GATA transcription factors directly regulate the Parkinson's disease-linked gene alpha-synuclein.Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10907-12. doi: 10.1073/pnas.0802437105. Epub 2008 Jul 31.
40 GATA factors promote ER integrity and -cell survival and contribute to type 1 diabetes risk.Mol Endocrinol. 2014 Jan;28(1):28-39. doi: 10.1210/me.2013-1265. Epub 2013 Jan 1.
41 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.
42 Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
43 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.