Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL07TLS)

• DOT Name: Endothelial differentiation-related factor 1 (EDF1)
• Synonyms: EDF-1; Multiprotein-bridging factor 1; MBF1
• Gene Name: EDF1
• Related Disease: Age-related macular degeneration
• UniProt ID: EDF1_HUMAN
• PDB ID: 1X57; 6ZVH
• Pfam ID: PF01381 ; PF08523
• Sequence:
  MAESDWDTVTVLRKKGPTAAQAKSKQAILAAQRRGEDVETSKKWAAGQNKQHSITKNTAK
  LDRETEELHHDRVTLEVGKVIQQGRQSKGLTQKDLATKINEKPQVIADYESGRAIPNNQV
  LGKIERAIGLKLRGKDIGKPIEKGPRAK
• Function: Transcriptional coactivator stimulating NR5A1 and ligand-dependent NR1H3/LXRA and PPARG transcriptional activities. Enhances the DNA-binding activity of ATF1, ATF2, CREB1 and NR5A1. Regulates nitric oxid synthase activity probably by sequestering calmodulin in the cytoplasm. May function in endothelial cells differentiation, hormone-induced cardiomyocytes hypertrophy and lipid metabolism.
• Tissue Specificity: Expressed in brain, liver, lung, kidney and heart (at protein level). Ubiquitously expressed. More abundant in heart, pancreas, liver, intestine and adipose tissues.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	moderate	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Endothelial differentiation-related factor 1 (EDF1) affects the response to substance of Afimoxifene.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endothelial differentiation-related factor 1 (EDF1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Endothelial differentiation-related factor 1 (EDF1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endothelial differentiation-related factor 1 (EDF1).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Endothelial differentiation-related factor 1 (EDF1).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Endothelial differentiation-related factor 1 (EDF1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endothelial differentiation-related factor 1 (EDF1).	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Endothelial differentiation-related factor 1 (EDF1).	[5]

References

• [1] Gene expression profiles of primary retinal pigment epithelial cells from apolipoprotein E knockout and human apolipoprotein E2 transgenic mice.Genet Mol Res. 2015 Mar 13;14(1):1855-67. doi: 10.4238/2015.March.13.14.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] 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.
• [4] 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.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2730-5. doi: 10.1073/pnas.1018872108. Epub 2011 Apr 11.