Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEH0BFG)

DOT Name TLE family member 5 (TLE5)
Synonyms Amino-terminal enhancer of split; Amino enhancer of split; Gp130-associated protein GAM; Grg-5; Groucho-related protein 5; Protein ESP1; Protein GRG; TLE family member 5, transcriptional modulator
Gene Name TLE5
Related Disease
Epilepsy ( )
Lung adenocarcinoma ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Alzheimer disease ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Cystic fibrosis ( )
Depression ( )
Myocardial ischemia ( )
Polycystic ovarian syndrome ( )
Prostate cancer ( )
Prostate carcinoma ( )
Colonic neoplasm ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Generalized anxiety disorder ( )
Parkinson disease ( )
Type-1/2 diabetes ( )
UniProt ID
TLE5_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF03920
Sequence
MMFPQSRHSGSSHLPQQLKFTTSDSCDRIKDEFQLLQAQYHSLKLECDKLASEKSEMQRH
YVMYYEMSYGLNIEMHKQAEIVKRLNGICAQVLPYLSQEHQQQVLGAIERAKQVTAPELN
SIIRQQLQAHQLSQLQALALPLTPLPVGLQPPSLPAVSAGTGLLSLSALGSQAHLSKEDK
NGHDGDTHQEDDGEKSD
Function
Transcriptional corepressor. Acts as a dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Essential for the transcriptional repressor activity of SIX3 during retina and lens development.
Tissue Specificity Found predominantly in muscle, heart and Placenta. In fetal tissues, abundantly expressed in the heart, lung, kidney, brain and liver.
Reactome Pathway
Repression of WNT target genes (R-HSA-4641265 )

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Epilepsy DISBB28L Definitive Genetic Variation [1]
Lung adenocarcinoma DISD51WR Definitive Altered Expression [2]
Acute monocytic leukemia DIS28NEL Strong Biomarker [3]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Genetic Variation [5]
Colon cancer DISVC52G Strong Biomarker [6]
Colon carcinoma DISJYKUO Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [7]
Cystic fibrosis DIS2OK1Q Strong Altered Expression [8]
Depression DIS3XJ69 Strong Genetic Variation [9]
Myocardial ischemia DISFTVXF Strong Biomarker [10]
Polycystic ovarian syndrome DISZ2BNG Strong Biomarker [11]
Prostate cancer DISF190Y Strong Biomarker [6]
Prostate carcinoma DISMJPLE Strong Biomarker [6]
Colonic neoplasm DISSZ04P moderate Altered Expression [12]
Metastatic malignant neoplasm DIS86UK6 moderate Altered Expression [12]
Neoplasm DISZKGEW moderate Biomarker [13]
Generalized anxiety disorder DISPSQCW Limited Biomarker [14]
Parkinson disease DISQVHKL Limited Biomarker [15]
Type-1/2 diabetes DISIUHAP Limited Biomarker [16]
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⏷ Show the Full List of 21 Disease(s)
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 TLE family member 5 (TLE5). [17]
Tretinoin DM49DUI Approved Tretinoin increases the expression of TLE family member 5 (TLE5). [18]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of TLE family member 5 (TLE5). [19]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of TLE family member 5 (TLE5). [20]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of TLE family member 5 (TLE5). [21]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of TLE family member 5 (TLE5). [22]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of TLE family member 5 (TLE5). [23]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of TLE family member 5 (TLE5). [24]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of TLE family member 5 (TLE5). [25]
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⏷ Show the Full List of 9 Drug(s)

References

1 Methodological standards for invitro models of epilepsy and epileptic seizures. A TASK1-WG4 report of the AES/ILAE Translational Task Force of the ILAE.Epilepsia. 2017 Nov;58 Suppl 4(Suppl 4):40-52. doi: 10.1111/epi.13901.
2 Grg1 acts as a lung-specific oncogene in a transgenic mouse model.Cancer Res. 2006 Feb 1;66(3):1294-301. doi: 10.1158/0008-5472.CAN-05-1634.
3 AML1/ETO induces self-renewal in hematopoietic progenitor cells via the Groucho-related amino-terminal AES protein.Blood. 2011 Apr 21;117(16):4328-37. doi: 10.1182/blood-2009-09-242545. Epub 2011 Jan 18.
4 Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions.Sci Rep. 2018 Sep 13;8(1):13790. doi: 10.1038/s41598-018-31696-9.
5 Apathy in Preclinical Alzheimer's Disease: Psychometric Validation of the Apathy Evaluation Scale.Am J Alzheimers Dis Other Demen. 2019 Feb;34(1):16-22. doi: 10.1177/1533317518794020. Epub 2018 Aug 14.
6 Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer.Cancer Sci. 2017 Apr;108(4):744-752. doi: 10.1111/cas.13187. Epub 2017 Apr 12.
7 Characterization of Aes nuclear foci in colorectal cancer cells.J Biochem. 2016 Jan;159(1):133-40. doi: 10.1093/jb/mvv077. Epub 2015 Jul 29.
8 Secretome of transmissible Pseudomonas aeruginosa AES-1R grown in a cystic fibrosis lung-like environment.J Proteome Res. 2013 Dec 6;12(12):5357-69. doi: 10.1021/pr4007365. Epub 2013 Oct 9.
9 Consequences of persistent depression and apathy in first-episode psychosis - A one-year follow-up study.Compr Psychiatry. 2018 Oct;86:60-66. doi: 10.1016/j.comppsych.2018.07.015. Epub 2018 Jul 29.
10 Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.J Thorac Cardiovasc Surg. 2005 Oct;130(4):1151. doi: 10.1016/j.jtcvs.2005.06.027.
11 The risk of metabolic syndrome in polycystic ovary syndrome: A systematic review and meta-analysis.Clin Endocrinol (Oxf). 2018 Feb;88(2):169-184. doi: 10.1111/cen.13477. Epub 2017 Oct 16.
12 Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2.Cancer Sci. 2016 Nov;107(11):1622-1631. doi: 10.1111/cas.13063.
13 Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer.J Med Chem. 2019 Mar 14;62(5):2651-2665. doi: 10.1021/acs.jmedchem.8b01957. Epub 2019 Mar 6.
14 Apathy in people with epilepsy and its clinical significance: A case-control study.Seizure. 2017 Oct;51:80-86. doi: 10.1016/j.seizure.2017.08.003. Epub 2017 Aug 8.
15 Metallomic profiling and linkage map analysis of early Parkinson's disease: a new insight to aluminum marker for the possible diagnosis.PLoS One. 2010 Jun 22;5(6):e11252. doi: 10.1371/journal.pone.0011252.
16 Polymer-free amphilimus-eluting stent versus biodegradable polymer biolimus-eluting stent in patients with and without diabetes mellitus.Int J Cardiol. 2017 Oct 15;245:69-76. doi: 10.1016/j.ijcard.2017.06.028.
17 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
18 Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
19 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
20 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.
21 Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
22 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
23 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
24 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
25 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.