Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFWZE51)

• DOT Name: Transcription factor COE2 (EBF2)
• Synonyms: Early B-cell factor 2; EBF-2
• Gene Name: EBF2
• Related Disease:
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Bone osteosarcoma
  Breast carcinoma
  Cardiovascular disease
  Kallmann syndrome
  Obesity
  Osteosarcoma
  Peripheral neuropathy
  Prostate cancer
  Prostate carcinoma
  Type-1/2 diabetes
  Venous thromboembolism
• UniProt ID: COE2_HUMAN
• Pfam ID: PF16422 ; PF16423 ; PF01833
• Sequence:
  MFGIQDTLGRGPTLKEKSLGAEMDSVRSWVRNVGVVDANVAAQSGVALSRAHFEKQPPSN
  LRKSNFFHFVLALYDRQGQPVEIERTAFVDFVENDKEQGNEKTNNGTHYKLQLLYSNGVR
  TEQDLYVRLIDSVTKQPIAYEGQNKNPEMCRVLLTHEVMCSRCCEKKSCGNRNETPSDPV
  IIDRFFLKFFLKCNQNCLKTAGNPRDMRRFQVVLSTTVNVDGHVLAVSDNMFVHNNSKHG
  RRARRLDPSEATPCIKAISPSEGWTTGGAMVIIIGDNFFDGLQVVFGTMLVWSELITPHA
  IRVQTPPRHIPGVVEVTLSYKSKQFCKGAPGRFIYTALNEPTIDYGFQRLQKVIPRHPGD
  PERLAKEMLLKRAADLVEALYGTPHNNQDIILKRAADIAEALYSVPRNPSQLPALSSSPA
  HSGMMGINSYGSQLGVSISESTQGNNQGYIRNTSSISPRGYSSSSTPQQSNYSTSSNSMN
  GYSNVPMANLGVPGSPGFLNGSPTGSPYGIMSSSPTVGSSSTSSILPFSSSVFPAVKQKS
  AFAPVIRPQGSPSPACSSGNGNGFRAMTGLVVPPM
• Function: Transcription factor that, in osteoblasts, activates the decoy receptor for RANKL, TNFRSF11B, which in turn regulates osteoclast differentiation. Acts in synergy with the Wnt-responsive LEF1/CTNNB1 pathway. Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3'.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Posttranslational Modification	[1]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[4]
Kallmann syndrome	DISO3HDG	Strong	Genetic Variation	[5]
Obesity	DIS47Y1K	Strong	Biomarker	[6]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[2]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[8]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[9]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[6]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[10]

7 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 COE2 (EBF2).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor COE2 (EBF2).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor COE2 (EBF2).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Transcription factor COE2 (EBF2).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcription factor COE2 (EBF2).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transcription factor COE2 (EBF2).	[15]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Transcription factor COE2 (EBF2).	[16]

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 increases the methylation of Transcription factor COE2 (EBF2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription factor COE2 (EBF2).	[18]

References

• [1] A genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers.Mol Cancer. 2010 Feb 25;9:44. doi: 10.1186/1476-4598-9-44.
• [2] Potential Regulatory Effects of miR-182-3p in Osteosarcoma via Targeting EBF2.Biomed Res Int. 2019 Mar 12;2019:4897905. doi: 10.1155/2019/4897905. eCollection 2019.
• [3] 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.
• [4] 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.
• [5] Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann syndrome and normosmic hypogonadotropic hypogonadism patients.J Endocrinol. 2005 Dec;187(3):361-8. doi: 10.1677/joe.1.06103.
• [6] Id1 Promotes Obesity by Suppressing Brown Adipose Thermogenesis and White Adipose Browning.Diabetes. 2017 Jun;66(6):1611-1625. doi: 10.2337/db16-1079. Epub 2017 Mar 7.
• [7] Both Schwann cell and axonal defects cause motor peripheral neuropathy in Ebf2-/- mice.Neurobiol Dis. 2011 Apr;42(1):73-84. doi: 10.1016/j.nbd.2011.01.006. Epub 2011 Jan 8.
• [8] Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.Nat Genet. 2013 Apr;45(4):385-91, 391e1-2. doi: 10.1038/ng.2560.
• [9] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [10] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] 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.
• [13] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [17] 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.
• [18] 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.