Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGK0V7W)

• DOT Name: Transcription factor COE4 (EBF4)
• Synonyms: Early B-cell factor 4; EBF-4; Olf-1/EBF-like 4; O/E-4; OE-4
• Gene Name: EBF4
• UniProt ID: COE4_HUMAN
• Pfam ID: PF16422 ; PF16423 ; PF01833
• Sequence:
  MFPAQDALPRSGLNLKEEPLLPAGLGSVRSWMQGAGILDASTAAQSGVGLARAHFEKQPP
  SNLRKSNFFHFVLAMYDRQGQPVEVERTAFIDFVEKDREPGAEKTNNGIHYRLRLVYNNG
  LRTEQDLYVRLIDSMSKQAIIYEGQDKNPEMCRVLLTHEIMCSRCCDRKSCGNRNETPSD
  PVIIDRFFLKFFLKCNQNCLKNAGNPRDMRRFQVVVSTTVSVDGHVLAVSDNMFVHNNSK
  HGRRARRLDPSEAATPCIKAISPGEGWTTGGATVIVIGDNFFDGLQVVFGNVLVWSELIT
  PHAIRVQTPPRHIPGVVEVTLSYKSKQFCKGCPGRFVYTALNEPTIDYGFQRLQKVIPRH
  PGDPERLPKEVLLKRAADLAEALYGVPGSNQELLLKRAADVAEALYSTPRAPGPLAPLAP
  SHPHPAVVGINAFSSPLAIAVGDATPGPEPGYARSCSSASPRGFAPSPGSQQSGYGGGLG
  AGLGGYGAPGVAGLGVPGSPSFLNGSTATSPFAIMPSSPPLAAASSMSLPAAAPTTSVFS
  FSPVNMISAVKQRSAFAPVLRPPSSPPQACPRAHGEGLPDQSFEDSDKFHSPARGLQGLA
  YS
• Function: Transcription factor. Binds to specific sequence motif 5'-CCCNNG[GA]G-3' in regulatory elements of putative target immunoregulatory genes such as NKG7, GZMA, and TBX21. Positively modulates transcription of NKG7. May play a role in regulating FAS/CD95-mediated apoptosis in cytotoxic NK cells and T-cells, probably downstream of interleukin IL2 signaling.
• Tissue Specificity: Most highly expressed in cytotoxic NK cells, especially CD16(+) NK cells, followed by CD8(+) T-cells.

Molecular Interaction Atlas (MIA) of This DOT

2 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 COE4 (EBF4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor COE4 (EBF4).	[5]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor COE4 (EBF4).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor COE4 (EBF4).	[3]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Transcription factor COE4 (EBF4).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor COE4 (EBF4).	[6]

References

• [1] 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.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] 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.
• [6] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.