Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO81B63)

DOT Name Transcription factor GATA-5 (GATA5)
Synonyms GATA-binding factor 5
Gene Name GATA5
Related Disease
Colon cancer ( )
Colon carcinoma ( )
Esophageal adenocarcinoma ( )
Squamous cell carcinoma ( )
Adenoma ( )
Advanced cancer ( )
Aorta coarctation ( )
Aortic valve disease 1 ( )
Aortic valve disorder ( )
Atrial fibrillation ( )
Breast cancer ( )
Breast carcinoma ( )
Cholangiocarcinoma ( )
Clear cell renal carcinoma ( )
Colorectal neoplasm ( )
Congenital contractural arachnodactyly ( )
Congenital heart disease ( )
Dilated cardiomyopathy 1A ( )
High blood pressure ( )
Kidney cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Neoplasm ( )
Pancreatic cancer ( )
Pancreatic tumour ( )
Renal cell carcinoma ( )
Ventricular septal defect ( )
Benign prostatic hyperplasia ( )
Carcinoma ( )
Cardiac disease ( )
Essential hypertension ( )
Hepatocellular carcinoma ( )
leukaemia ( )
Leukemia ( )
Familial atrial fibrillation ( )
Familial bicuspid aortic valve ( )
Tetralogy of fallot ( )
Gastric neoplasm ( )
Adenocarcinoma ( )
Aortic valve stenosis ( )
Arrhythmia ( )
Colorectal carcinoma ( )
Congenital heart defects, multiple types, 5 ( )
Ductal breast carcinoma in situ ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
UniProt ID
GATA5_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00320 ; PF05349
Sequence
MYQSLALAASPRQAAYADSGSFLHAPGAGSPMFVPPARVPSMLSYLSGCEPSPQPPELAA
RPGWAQTATADSSAFGPGSPHPPAAHPPGATAFPFAHSPSGPGSGGSAGGRDGSAYQGAL
LPREQFAAPLGRPVGTSYSATYPAYVSPDVAQSWTAGPFDGSVLHGLPGRRPTFVSDFLE
EFPGEGRECVNCGALSTPLWRRDGTGHYLCNACGLYHKMNGVNRPLVRPQKRLSSSRRAG
LCCTNCHTTNTTLWRRNSEGEPVCNACGLYMKLHGVPRPLAMKKESIQTRKRKPKTIAKA
RGSSGSTRNASASPSAVASTDSSAATSKAKPSLASPVCPGPSMAPQASGQEDDSLAPGHL
EFKFEPEDFAFPSTAPSPQAGLRGALRQEAWCALALA
Function
Transcription factor required during cardiovascular development. Plays an important role in the transcriptional program(s) that underlies smooth muscle cell diversity. Binds to the functionally important CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C transcriptional enhancer.
Reactome Pathway
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colon cancer DISVC52G Definitive Biomarker [1]
Colon carcinoma DISJYKUO Definitive Biomarker [1]
Esophageal adenocarcinoma DISODWFP Definitive Posttranslational Modification [1]
Squamous cell carcinoma DISQVIFL Definitive Posttranslational Modification [1]
Adenoma DIS78ZEV Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Aorta coarctation DISAFXDJ Strong Genetic Variation [4]
Aortic valve disease 1 DIS3JI56 Strong GermlineCausalMutation [5]
Aortic valve disorder DISKLYD7 Strong GermlineCausalMutation [5]
Atrial fibrillation DIS15W6U Strong Genetic Variation [6]
Breast cancer DIS7DPX1 Strong Altered Expression [7]
Breast carcinoma DIS2UE88 Strong Altered Expression [7]
Cholangiocarcinoma DIS71F6X Strong Biomarker [8]
Clear cell renal carcinoma DISBXRFJ Strong Posttranslational Modification [9]
Colorectal neoplasm DISR1UCN Strong Biomarker [10]
Congenital contractural arachnodactyly DISOM1K7 Strong Biomarker [8]
Congenital heart disease DISQBA23 Strong Genetic Variation [5]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Genetic Variation [11]
High blood pressure DISY2OHH Strong Biomarker [12]
Kidney cancer DISBIPKM Strong Biomarker [13]
Lung cancer DISCM4YA Strong Biomarker [14]
Lung carcinoma DISTR26C Strong Biomarker [14]
Lung neoplasm DISVARNB Strong Posttranslational Modification [15]
Neoplasm DISZKGEW Strong Biomarker [16]
Pancreatic cancer DISJC981 Strong Posttranslational Modification [17]
Pancreatic tumour DIS3U0LK Strong Posttranslational Modification [17]
Renal cell carcinoma DISQZ2X8 Strong Posttranslational Modification [9]
Ventricular septal defect DISICO41 Strong Genetic Variation [18]
Benign prostatic hyperplasia DISI3CW2 moderate Genetic Variation [19]
Carcinoma DISH9F1N moderate Posttranslational Modification [20]
Cardiac disease DISVO1I5 moderate Genetic Variation [21]
Essential hypertension DIS7WI98 moderate Biomarker [12]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [3]
leukaemia DISS7D1V moderate Biomarker [22]
Leukemia DISNAKFL moderate Biomarker [22]
Familial atrial fibrillation DISL4AGF Supportive Autosomal dominant [23]
Familial bicuspid aortic valve DISL0BRK Supportive Autosomal dominant [5]
Tetralogy of fallot DISMHFNW Supportive Autosomal dominant [24]
Gastric neoplasm DISOKN4Y Disputed Posttranslational Modification [25]
Adenocarcinoma DIS3IHTY Limited Genetic Variation [26]
Aortic valve stenosis DISW7AQ9 Limited Biomarker [27]
Arrhythmia DISFF2NI Limited Genetic Variation [28]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [2]
Congenital heart defects, multiple types, 5 DISXPQ2U Limited Unknown [29]
Ductal breast carcinoma in situ DISLCJY7 Limited Posttranslational Modification [30]
Epithelial ovarian cancer DIS56MH2 Limited Biomarker [31]
Ovarian cancer DISZJHAP Limited Biomarker [31]
Ovarian neoplasm DISEAFTY Limited Biomarker [31]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Transcription factor GATA-5 (GATA5). [32]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Transcription factor GATA-5 (GATA5). [35]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Transcription factor GATA-5 (GATA5). [38]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Transcription factor GATA-5 (GATA5). [40]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transcription factor GATA-5 (GATA5). [33]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Transcription factor GATA-5 (GATA5). [34]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Transcription factor GATA-5 (GATA5). [34]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Transcription factor GATA-5 (GATA5). [36]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Transcription factor GATA-5 (GATA5). [37]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Transcription factor GATA-5 (GATA5). [39]
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⏷ Show the Full List of 6 Drug(s)

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 Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive biomarker for colorectal cancer and adenomas.World J Gastroenterol. 2015 Mar 7;21(9):2629-37. doi: 10.3748/wjg.v21.i9.2629.
3 GATA5 inhibits hepatocellular carcinoma cells malignant behaviours by blocking expression of reprogramming genes.J Cell Mol Med. 2019 Apr;23(4):2536-2548. doi: 10.1111/jcmm.14144. Epub 2019 Jan 22.
4 Rare GATA5 sequence variants identified in individuals with bicuspid aortic valve.Pediatr Res. 2014 Aug;76(2):211-6. doi: 10.1038/pr.2014.67. Epub 2014 May 5.
5 GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve. Int J Mol Med. 2014 May;33(5):1219-26. doi: 10.3892/ijmm.2014.1700. Epub 2014 Mar 14.
6 A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation.Int J Mol Med. 2013 Jan;31(1):43-50. doi: 10.3892/ijmm.2012.1189. Epub 2012 Nov 20.
7 GATA5 activation of the progesterone receptor gene promoter in breast cancer cells is influenced by the +331G/A polymorphism.Cancer Res. 2006 Feb 1;66(3):1384-90. doi: 10.1158/0008-5472.CAN-05-2715.
8 Methylation-Mediated Silencing of GATA5 Gene Suppresses Cholangiocarcinoma Cell Proliferation and Metastasis.Transl Oncol. 2018 Jun;11(3):585-592. doi: 10.1016/j.tranon.2018.01.023. Epub 2018 Mar 13.
9 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.
10 GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer.Clin Cancer Res. 2009 Jun 15;15(12):3990-7. doi: 10.1158/1078-0432.CCR-09-0055. Epub 2009 Jun 9.
11 GATA5 loss-of-function mutation in familial dilated cardiomyopathy.Int J Mol Med. 2015 Mar;35(3):763-70. doi: 10.3892/ijmm.2014.2050. Epub 2014 Dec 29.
12 Endothelial Gata5 transcription factor regulates blood pressure.Nat Commun. 2015 Nov 30;6:8835. doi: 10.1038/ncomms9835.
13 GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression.BJU Int. 2012 Jul;110(2 Pt 2):E144-52. doi: 10.1111/j.1464-410X.2011.10862.x. Epub 2012 Jan 30.
14 Radiation-induced lung adenocarcinoma is associated with increased frequency of genes inactivated by promoter hypermethylation.Radiat Res. 2007 Oct;168(4):409-14. doi: 10.1667/RR0825.1.
15 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.
16 Analysis of the role of mutations in the KMT2D histone lysine methyltransferase in bladder cancer.FEBS Open Bio. 2019 Feb 21;9(4):693-706. doi: 10.1002/2211-5463.12600. eCollection 2019 Apr.
17 Evaluation of GATA-4 and GATA-5 methylation profiles in human pancreatic cancers indicate promoter methylation patterns distinct from other human tumor types.Cancer Biol Ther. 2007 Oct;6(10):1546-52. doi: 10.4161/cbt.6.10.4708. Epub 2007 Jul 7.
18 Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects.World J Pediatr. 2014 Nov;10(4):348-53. doi: 10.1007/s12519-014-0511-z. Epub 2014 Dec 17.
19 Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA.Nat Commun. 2018 Nov 8;9(1):4568. doi: 10.1038/s41467-018-06920-9.
20 Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas.World J Gastroenterol. 2010 Mar 14;16(10):1201-8. doi: 10.3748/wjg.v16.i10.1201.
21 Compound heterozygous GATA5 mutations in a girl with hydrops fetalis, congenital heart defects and genital anomalies.Hum Genet. 2017 Mar;136(3):339-346. doi: 10.1007/s00439-017-1762-2. Epub 2017 Feb 8.
22 Direct Reprogramming of Fibroblasts Into Smooth Muscle-Like Cells With Defined Transcription Factors-Brief Report.Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2191-2197. doi: 10.1161/ATVBAHA.118.310870.
23 Mutational spectrum of the GATA5 gene associated with familial atrial fibrillation. Int J Cardiol. 2012 May 31;157(2):305-7. doi: 10.1016/j.ijcard.2012.03.132. Epub 2012 Apr 6.
24 GATA5 loss-of-function mutations underlie tetralogy of fallot. Int J Med Sci. 2013;10(1):34-42. doi: 10.7150/ijms.5270. Epub 2012 Dec 10.
25 GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer.Mol Cell Biol. 2003 Dec;23(23):8429-39. doi: 10.1128/MCB.23.23.8429-8439.2003.
26 Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors.PLoS One. 2011;6(10):e25985. doi: 10.1371/journal.pone.0025985. Epub 2011 Oct 20.
27 GATA5 interacts with GATA4 and GATA6 in outflow tract development.Dev Biol. 2011 Oct 15;358(2):368-78. doi: 10.1016/j.ydbio.2011.07.037. Epub 2011 Aug 4.
28 Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation.Clinics (Sao Paulo). 2012 Dec;67(12):1393-9. doi: 10.6061/clinics/2012(12)08.
29 Prevalence and spectrum of GATA5 mutations associated with congenital heart disease. Int J Cardiol. 2013 May 25;165(3):570-3. doi: 10.1016/j.ijcard.2012.09.039. Epub 2012 Sep 30.
30 Promoter hypermethylation in ductal carcinoma in situ of the male breast.Endocr Relat Cancer. 2019 Jun;26(6):575-584. doi: 10.1530/ERC-18-0485.
31 Methylation analysis of tumour suppressor genes in ovarian cancer using MS-MLPA.Folia Biol (Praha). 2012;58(6):246-50.
32 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.
33 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
34 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
35 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.
36 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
37 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
38 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.
39 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.
40 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.