Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ61YYH)

DOT Name Transcription factor COE1 (EBF1)
Synonyms O/E-1; OE-1; Early B-cell factor
Gene Name EBF1
Related Disease
Lipodystrophy ( )
OPTN-related open angle glaucoma ( )
Acute leukaemia ( )
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Anorexia nervosa cachexia ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autism ( )
B-cell neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiovascular disease ( )
Childhood myelodysplastic syndrome ( )
Classic Hodgkin lymphoma ( )
Colorectal carcinoma ( )
Congenital contractural arachnodactyly ( )
Coronary heart disease ( )
Follicular lymphoma ( )
Myelodysplastic syndrome ( )
Orthostatic hypotension ( )
Renal hypoplasia ( )
Acute lymphocytic leukaemia ( )
Childhood acute lymphoblastic leukemia ( )
Hepatocellular carcinoma ( )
Neuroblastoma ( )
Small lymphocytic lymphoma ( )
Varicose veins ( )
Multiple sclerosis ( )
Nervous system disease ( )
Adult respiratory distress syndrome ( )
Alopecia ( )
Androgenetic alopecia ( )
Baldness, male pattern ( )
Coronary atherosclerosis ( )
Helicoid peripapillary chorioretinal degeneration ( )
Melanoma ( )
Nasopharyngeal carcinoma ( )
Systemic lupus erythematosus ( )
Type-1/2 diabetes ( )
UniProt ID
COE1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3LYR; 3MQI
Pfam ID
PF16422 ; PF16423 ; PF01833
Sequence
MFGIQESIQRSGSSMKEEPLGSGMNAVRTWMQGAGVLDANTAAQSGVGLARAHFEKQPPS
NLRKSNFFHFVLALYDRQGQPVEIERTAFVGFVEKEKEANSEKTNNGIHYRLQLLYSNGI
RTEQDFYVRLIDSMTKQAIVYEGQDKNPEMCRVLLTHEIMCSRCCDKKSCGNRNETPSDP
VIIDRFFLKFFLKCNQNCLKNAGNPRDMRRFQVVVSTTVNVDGHVLAVSDNMFVHNNSKH
GRRARRLDPSEGTPSYLEHATPCIKAISPSEGWTTGGATVIIIGDNFFDGLQVIFGTMLV
WSELITPHAIRVQTPPRHIPGVVEVTLSYKSKQFCKGTPGRFIYTALNEPTIDYGFQRLQ
KVIPRHPGDPERLPKEVILKRAADLVEALYGMPHNNQEIILKRAADIAEALYSVPRNHNQ
LPALANTSVHAGMMGVNSFSGQLAVNVSEASQATNQGFTRNSSSVSPHGYVPSTTPQQTN
YNSVTTSMNGYGSAAMSNLGGSPTFLNGSAANSPYAIVPSSPTMASSTSLPSNCSSSSGI
FSFSPANMVSAVKQKSAFAPVVRPQTSPPPTCTSTNGNSLQAISGMIVPPM
Function
Key pioneer transcription factor of B-cell specification and commitment. Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3'. Operates in a transcription factor network to activate B-cell-specific genes and repress genes associated with alternative cell fates. For instance, positively regulates many B-cell specific genes including BCR or CD40 while repressing genes that direct cells into alternative lineages, including GATA3 and TCF7 for the T-cell lineage. In addition to its role during lymphopoiesis, controls the thermogenic gene program in adipocytes during development and in response to environmental cold; (Microbial infection) Acts as a chromatin anchor for Epstein-Barr virus EBNA2 to mediate the assembly of EBNA2 chromatin complexes in B-cells. In addition, binds to the viral LMP1 proximal promoter and promotes its expression during latency.
Reactome Pathway
Expression and translocation of olfactory receptors (R-HSA-9752946 )
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lipodystrophy DIS3SGVD Definitive Biomarker [1]
OPTN-related open angle glaucoma DISDR98A Definitive Altered Expression [2]
Acute leukaemia DISDQFDI Strong Genetic Variation [3]
Acute myelogenous leukaemia DISCSPTN Strong Genetic Variation [4]
Advanced cancer DISAT1Z9 Strong Altered Expression [5]
Anorexia nervosa cachexia DISFO5RQ Strong Genetic Variation [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Autism DISV4V1Z Strong Genetic Variation [8]
B-cell neoplasm DISVY326 Strong Altered Expression [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Genetic Variation [11]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [12]
Childhood myelodysplastic syndrome DISMN80I Strong Biomarker [9]
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [13]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [14]
Congenital contractural arachnodactyly DISOM1K7 Strong Biomarker [5]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [15]
Follicular lymphoma DISVEUR6 Strong Biomarker [16]
Myelodysplastic syndrome DISYHNUI Strong Genetic Variation [9]
Orthostatic hypotension DISBKQGT Strong Genetic Variation [17]
Renal hypoplasia DISJ5F10 Strong Biomarker [18]
Acute lymphocytic leukaemia DISPX75S moderate Biomarker [19]
Childhood acute lymphoblastic leukemia DISJ5D6U moderate Biomarker [19]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [20]
Neuroblastoma DISVZBI4 moderate Altered Expression [21]
Small lymphocytic lymphoma DIS30POX moderate Altered Expression [22]
Varicose veins DISIMBN2 moderate Genetic Variation [23]
Multiple sclerosis DISB2WZI Disputed Genetic Variation [24]
Nervous system disease DISJ7GGT Disputed Genetic Variation [24]
Adult respiratory distress syndrome DISIJV47 Limited Biomarker [25]
Alopecia DIS37HU4 Limited Genetic Variation [26]
Androgenetic alopecia DISSJR1P Limited Genetic Variation [27]
Baldness, male pattern DIS9C9RO Limited Genetic Variation [27]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [28]
Helicoid peripapillary chorioretinal degeneration DISFSS5N Limited Biomarker [29]
Melanoma DIS1RRCY Limited Genetic Variation [30]
Nasopharyngeal carcinoma DISAOTQ0 Limited Altered Expression [31]
Systemic lupus erythematosus DISI1SZ7 Limited Genetic Variation [29]
Type-1/2 diabetes DISIUHAP Limited Biomarker [28]
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⏷ Show the Full List of 40 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 Transcription factor COE1 (EBF1). [32]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Transcription factor COE1 (EBF1). [33]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Transcription factor COE1 (EBF1). [34]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Transcription factor COE1 (EBF1). [35]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Transcription factor COE1 (EBF1). [36]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Transcription factor COE1 (EBF1). [36]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Transcription factor COE1 (EBF1). [37]
Exemestane DM9HPW3 Approved Exemestane increases the expression of Transcription factor COE1 (EBF1). [38]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Transcription factor COE1 (EBF1). [40]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Transcription factor COE1 (EBF1). [42]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Transcription factor COE1 (EBF1). [43]
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⏷ Show the Full List of 11 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 decreases the methylation of Transcription factor COE1 (EBF1). [39]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Transcription factor COE1 (EBF1). [41]
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References

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5 Prolonged oxidative stress down-regulates Early B cell factor 1 with inhibition of its tumor suppressive function against cholangiocarcinoma genesis.Redox Biol. 2018 Apr;14:637-644. doi: 10.1016/j.redox.2017.11.011. Epub 2017 Nov 13.
6 A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling.Sci Rep. 2017 Jun 19;7(1):3847. doi: 10.1038/s41598-017-01674-8.
7 Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation.Int J Mol Med. 2014 May;33(5):1355-63. doi: 10.3892/ijmm.2014.1692. Epub 2014 Mar 10.
8 Common Genetic Variants Link the Abnormalities in the Gut-Brain Axis in Prematurity and Autism.Cerebellum. 2019 Apr;18(2):255-265. doi: 10.1007/s12311-018-0970-1.
9 Retracted: EBF1 gene promotes the proliferation and inhibits the apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome through negative regulation of mitogen-activated protein kinase axis.J Cell Biochem. 2019 Feb;120(2):1407-1419. doi: 10.1002/jcb.27177. Epub 2018 Oct 18.
10 Lowly methylated region analysis identifies EBF1 as a potential epigenetic modifier in breast cancer.Epigenetics. 2017;12(11):964-972. doi: 10.1080/15592294.2017.1373919. Epub 2017 Nov 10.
11 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
12 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
13 Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma.Leukemia. 2013 Mar;27(3):671-9. doi: 10.1038/leu.2012.280. Epub 2012 Oct 1.
14 Ubiquitin specific peptidase 5 regulates colorectal cancer cell growth by stabilizing Tu translation elongation factor.Theranostics. 2019 May 31;9(14):4208-4220. doi: 10.7150/thno.33803. eCollection 2019.
15 EBF1 gene polymorphism and its interaction with smoking and drinking on the risk of coronary artery disease for Chinese patients.Biosci Rep. 2018 Jun 21;38(3):BSR20180324. doi: 10.1042/BSR20180324. Print 2018 Jun 29.
16 Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma.Nat Genet. 2014 Feb;46(2):176-181. doi: 10.1038/ng.2856. Epub 2013 Dec 22.
17 Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium.Eur Heart J. 2012 Sep;33(18):2331-41. doi: 10.1093/eurheartj/ehs058. Epub 2012 Apr 14.
18 Early B Cell Factor 1 (EBF1) Regulates Glomerular Development by Controlling Mesangial Maturation and Consequently COX-2 Expression.J Am Soc Nephrol. 2019 Sep;30(9):1559-1572. doi: 10.1681/ASN.2018070699. Epub 2019 Aug 12.
19 Prognostic significance of copy number alterations detected by multi-link probe amplification of multiple genes in adult acute lymphoblastic leukemia.Oncol Lett. 2018 Apr;15(4):5359-5367. doi: 10.3892/ol.2018.7985. Epub 2018 Feb 7.
20 Amphiphilic poly-N-vinylpyrrolidone nanoparticles as carriers for non-steroidal, anti-inflammatory drugs: In vitro cytotoxicity and in vivo acute toxicity study.Nanomedicine. 2017 Apr;13(3):1021-1030. doi: 10.1016/j.nano.2016.11.006. Epub 2016 Nov 22.
21 Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression.BMC Cancer. 2004 Nov 15;4:80. doi: 10.1186/1471-2407-4-80.
22 Cellular origin and pathophysiology of chronic lymphocytic leukemia.J Exp Med. 2012 Nov 19;209(12):2183-98. doi: 10.1084/jem.20120833. Epub 2012 Oct 22.
23 Varicose veins of lower extremities: Insights from the first large-scale genetic study.PLoS Genet. 2019 Apr 18;15(4):e1008110. doi: 10.1371/journal.pgen.1008110. eCollection 2019 Apr.
24 Early B-cell Factor gene association with multiple sclerosis in the Spanish population.BMC Neurol. 2005 Oct 28;5:19. doi: 10.1186/1471-2377-5-19.
25 MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome.BMC Med Genomics. 2014 Jul 28;7:46. doi: 10.1186/1755-8794-7-46.
26 Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
27 GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
28 Association in a Chinese population of a genetic variation in the early B-cell factor 1 gene with coronary artery disease.BMC Cardiovasc Disord. 2017 Feb 10;17(1):57. doi: 10.1186/s12872-017-0489-2.
29 Population-Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus.Arthritis Rheumatol. 2020 Feb;72(2):282-291. doi: 10.1002/art.41083. Epub 2019 Dec 26.
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31 Natural Variations in BRLF1 Promoter Contribute to the Elevated Reactivation Level of Epstein-Barr Virus in Endemic Areas of Nasopharyngeal Carcinoma.EBioMedicine. 2018 Nov;37:101-109. doi: 10.1016/j.ebiom.2018.10.065. Epub 2018 Nov 9.
32 In vitro assessment of drug-induced liver steatosis based on human dermal stem cell-derived hepatic cells. Arch Toxicol. 2016 Mar;90(3):677-89. doi: 10.1007/s00204-015-1483-z. Epub 2015 Feb 26.
33 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
34 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.
35 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
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37 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
38 Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
39 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.
40 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
41 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.
42 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
43 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.