Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZUQY5L)

DOT Name Class E basic helix-loop-helix protein 22 (BHLHE22)
Synonyms bHLHe22; Class B basic helix-loop-helix protein 5; bHLHb5; Trinucleotide repeat-containing gene 20 protein
Gene Name BHLHE22
Related Disease
Epithelial ovarian cancer ( )
Invasive breast carcinoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate cancer ( )
Adult glioblastoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cholangiocarcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal neoplasm ( )
Depression ( )
Diphtheria ( )
Duane retraction syndrome ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Epilepsy ( )
Glanzmann thrombasthenia ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Hereditary chronic pancreatitis ( )
Hermansky-Pudlak syndrome ( )
Lung carcinoma ( )
Malignant glioma ( )
Mental disorder ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Pancreatic tumour ( )
Prostate carcinoma ( )
Squamous cell carcinoma ( )
Adenocarcinoma ( )
Atherosclerosis ( )
Bladder cancer ( )
Primitive neuroectodermal tumor ( )
Urinary bladder cancer ( )
Age-related macular degeneration ( )
Arteriosclerosis ( )
Bone osteosarcoma ( )
Hyperglycemia ( )
Lewy body dementia ( )
Osteosarcoma ( )
Pancreatic cancer ( )
UniProt ID
BHE22_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00010
Sequence
MERGMHLGAAAAGEDDLFLHKSLSASTSKRLEAAFRSTPPGMDLSLAPPPRERPASSSSS
PLGCFEPADPEGAGLLLPPPGGGGGGSAGSGGGGGGGVGVPGLLVGSAGVGGDPSLSSLP
AGAALCLKYGESASRGSVAESSGGEQSPDDDSDGRCELVLRAGVADPRASPGAGGGGAKA
AEGCSNAHLHGGASVPPGGLGGGGGGGSSSGSSGGGGGSGSGSGGSSSSSSSSSKKSKEQ
KALRLNINARERRRMHDLNDALDELRAVIPYAHSPSVRKLSKIATLLLAKNYILMQAQAL
EEMRRLVAYLNQGQAISAASLPSSAAAAAAAAALHPALGAYEQAAGYPFSAGLPPAASCP
EKCALFNSVSSSLCKQCTEKP
Function
Inhibits DNA binding of TCF3/E47 homodimers and TCF3 (E47)/NEUROD1 heterodimers and acts as a strong repressor of Neurod1 and Myod-responsive genes, probably by heterodimerization with class a basic helix-loop-helix factors. Despite the presence of an intact basic domain, does not bind to DNA. In the brain, may function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization. May be required for the survival of a specific population of inhibitory neurons in the superficial laminae of the spinal cord dorsal horn that may regulate pruritis. Seems to play a crucial role in the retinogenesis, in the specification of amacrine and bipolar subtypes. Forms with PRDM8 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation.
Tissue Specificity Brain-specific, with the highest expression in the cerebellum.
Reactome Pathway
Regulation of CDH11 gene transcription (R-HSA-9762293 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Epithelial ovarian cancer DIS56MH2 Definitive Altered Expression [1]
Invasive breast carcinoma DISANYTW Definitive Altered Expression [2]
Ovarian cancer DISZJHAP Definitive Altered Expression [1]
Ovarian neoplasm DISEAFTY Definitive Altered Expression [1]
Prostate cancer DISF190Y Definitive Altered Expression [3]
Adult glioblastoma DISVP4LU Strong Altered Expression [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Breast neoplasm DISNGJLM Strong Altered Expression [6]
Cholangiocarcinoma DIS71F6X Strong Biomarker [7]
Colon cancer DISVC52G Strong Biomarker [8]
Colon carcinoma DISJYKUO Strong Biomarker [8]
Colorectal neoplasm DISR1UCN Strong Biomarker [9]
Depression DIS3XJ69 Strong Genetic Variation [10]
Diphtheria DISZWM55 Strong Biomarker [11]
Duane retraction syndrome DISOEBK2 Strong Biomarker [12]
Endometrial cancer DISW0LMR Strong Biomarker [13]
Endometrial carcinoma DISXR5CY Strong Biomarker [13]
Epilepsy DISBB28L Strong Altered Expression [14]
Glanzmann thrombasthenia DISFGGTG Strong Biomarker [15]
Glioblastoma multiforme DISK8246 Strong Altered Expression [4]
Glioma DIS5RPEH Strong Altered Expression [16]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [7]
Hereditary chronic pancreatitis DISF0J1Q Strong Biomarker [17]
Hermansky-Pudlak syndrome DISCY0HQ Strong Genetic Variation [18]
Lung carcinoma DISTR26C Strong Altered Expression [19]
Malignant glioma DISFXKOV Strong Altered Expression [20]
Mental disorder DIS3J5R8 Strong Biomarker [10]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [21]
Neoplasm DISZKGEW Strong Altered Expression [5]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [22]
Pancreatic tumour DIS3U0LK Strong Altered Expression [23]
Prostate carcinoma DISMJPLE Strong Altered Expression [3]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [24]
Adenocarcinoma DIS3IHTY moderate Altered Expression [24]
Atherosclerosis DISMN9J3 moderate Biomarker [15]
Bladder cancer DISUHNM0 moderate Altered Expression [25]
Primitive neuroectodermal tumor DISFHXHA moderate Biomarker [26]
Urinary bladder cancer DISDV4T7 moderate Altered Expression [25]
Age-related macular degeneration DIS0XS2C Limited Altered Expression [27]
Arteriosclerosis DISK5QGC Limited Biomarker [15]
Bone osteosarcoma DIST1004 Limited Altered Expression [28]
Hyperglycemia DIS0BZB5 Limited Biomarker [29]
Lewy body dementia DISAE66J Limited Biomarker [30]
Osteosarcoma DISLQ7E2 Limited Altered Expression [28]
Pancreatic cancer DISJC981 Limited Biomarker [31]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Class E basic helix-loop-helix protein 22 (BHLHE22). [32]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Class E basic helix-loop-helix protein 22 (BHLHE22). [35]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Class E basic helix-loop-helix protein 22 (BHLHE22). [36]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cytarabine DMZD5QR Approved Cytarabine increases the expression of Class E basic helix-loop-helix protein 22 (BHLHE22). [33]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Class E basic helix-loop-helix protein 22 (BHLHE22). [34]
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References

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9 Class III -tubulin Expression in Colorectal Neoplasms Is a Potential Predictive Biomarker for Paclitaxel Response.Anticancer Res. 2019 Feb;39(2):655-662. doi: 10.21873/anticanres.13160.
10 The C825T Polymorphism of the G-Protein 3 Gene as a Risk Factor for Depression: A Meta-Analysis.PLoS One. 2015 Jul 6;10(7):e0132274. doi: 10.1371/journal.pone.0132274. eCollection 2015.
11 Auditory Neuropathy after Damage to Cochlear Spiral Ganglion Neurons in Mice Resulting from Conditional Expression of Diphtheria Toxin Receptors.Sci Rep. 2017 Jul 25;7(1):6409. doi: 10.1038/s41598-017-06600-6.
12 Functional and structural characterization of the human gene BHLHB5, encoding a basic helix-loop-helix transcription factor.Genomics. 2002 Sep;80(3):311-8. doi: 10.1006/geno.2002.6833.
13 Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings.Clin Epigenetics. 2019 Nov 28;11(1):170. doi: 10.1186/s13148-019-0765-3.
14 Nestin-expressing cell types in the temporal lobe and hippocampus: Morphology, differentiation, and proliferative capacity.Glia. 2018 Jan;66(1):62-77. doi: 10.1002/glia.23211. Epub 2017 Sep 19.
15 Patients with Glanzmann thrombasthenia lacking platelet glycoprotein alpha(IIb)beta(3) (GPIIb/IIIa) and alpha(v)beta(3) receptors are not protected from atherosclerosis.Circulation. 2002 Mar 5;105(9):1044-8. doi: 10.1161/hc0902.104676.
16 Hypoxia-inducible factor-2 (HIF-2), but not HIF-1, is essential for hypoxic induction of class III -tubulin expression in human glioblastoma cells.FEBS J. 2014 Dec;281(23):5220-36. doi: 10.1111/febs.13062. Epub 2014 Oct 13.
17 Ligand-dependent inequivalence of the and subunits of ferric human hemoglobin bound to haptoglobin.J Inorg Biochem. 2020 Jan;202:110814. doi: 10.1016/j.jinorgbio.2019.110814. Epub 2019 Sep 2.
18 Nonsense mutations in ADTB3A cause complete deficiency of the beta3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2.Pediatr Res. 2002 Feb;51(2):150-8. doi: 10.1203/00006450-200202000-00006.
19 Delineating the interaction of combretastatin A-4 with tubulin isotypes present in drug resistant human lung carcinoma using a molecular modeling approach.J Biomol Struct Dyn. 2020 Feb;38(2):426-438. doi: 10.1080/07391102.2019.1577174. Epub 2019 Mar 4.
20 Mitochondrial dysfunction in gliomas.Semin Pediatr Neurol. 2013 Sep;20(3):216-27. doi: 10.1016/j.spen.2013.09.003.
21 A Rationally Optimized Nanoparticle System for the Delivery of RNA Interference Therapeutics into Pancreatic Tumors in Vivo.Biomacromolecules. 2016 Jul 11;17(7):2337-51. doi: 10.1021/acs.biomac.6b00185. Epub 2016 Jun 28.
22 Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption.Cell Death Dis. 2018 Nov 14;9(11):1134. doi: 10.1038/s41419-018-1174-9.
23 The Use of Star Polymer Nanoparticles for theDelivery of siRNA to Mouse Orthotopic Pancreatic Tumor Models.Methods Mol Biol. 2019;1974:329-353. doi: 10.1007/978-1-4939-9220-1_23.
24 Biomarker expression and druggable gene alterations for development of an appropriate therapeutic protocol for pulmonary adenosquamous carcinoma.Histopathology. 2015 Jun;66(7):939-48. doi: 10.1111/his.12556. Epub 2015 Feb 5.
25 III-tubulin overexpression is linked to aggressive tumor features and genetic instability in urinary bladder cancer.Hum Pathol. 2017 Mar;61:210-220. doi: 10.1016/j.humpath.2016.11.005. Epub 2016 Dec 24.
26 Malignant glioma with primitive neuroectodermal tumor-like component (MG-PNET): novel microarray findings in a pediatric patient.Clin Neuropathol. 2016 Nov/Dec;35(6):353-367. doi: 10.5414/NP300942.
27 Neural stem/progenitor cells circulating in peripheral blood of patients with neovascular form of AMD: a novel view on pathophysiology.Graefes Arch Clin Exp Ophthalmol. 2011 Dec;249(12):1785-94. doi: 10.1007/s00417-011-1767-9. Epub 2011 Aug 17.
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30 Lewy Bodies and the Mechanisms of Neuronal Cell Death in Parkinson's Disease and Dementia with Lewy Bodies.Brain Pathol. 2017 Jan;27(1):3-12. doi: 10.1111/bpa.12344. Epub 2016 Jan 18.
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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.
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35 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.
36 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.