Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN27MJW)

• DOT Name: ELL-associated factor 1 (EAF1)
• Gene Name: EAF1
• Related Disease:
  leukaemia
  Leukemia
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
• UniProt ID: EAF1_HUMAN
• PDB ID: 7OKX; 7OKY
• Pfam ID: PF09816
• Sequence:
  MNGTANPLLDREEHCLRLGESFEKRPRASFHTIRYDFKPASIDTSCEGELQVGKGDEVTI
  TLPHIPGSTPPMTVFKGNKRPYQKDCVLIINHDTGEYVLEKLSSSIQVKKTRAEGSSKIQ
  ARMEQQPTRPPQTSQPPPPPPPMPFRAPTKPPVGPKTSPLKDNPSPEPQLDDIKRELRAE
  VDIIEQMSSSSGSSSSDSESSSGSDDDSSSSGGEDNGPASPPQPSHQQPYNSRPAVANGT
  SRPQGSNQLMNTLRNDLQLSESGSDSDD
• Function: Acts as a transcriptional transactivator of ELL and ELL2 elongation activities.
• Tissue Specificity: Strongly expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, prostate, testis, small intestine and colon. Poorly expressed in thymus.
• Reactome Pathway:
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
leukaemia	DISS7D1V	Strong	Biomarker	[1]
Leukemia	DISNAKFL	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of ELL-associated factor 1 (EAF1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ELL-associated factor 1 (EAF1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ELL-associated factor 1 (EAF1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ELL-associated factor 1 (EAF1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ELL-associated factor 1 (EAF1).	[8]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of ELL-associated factor 1 (EAF1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of ELL-associated factor 1 (EAF1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ELL-associated factor 1 (EAF1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ELL-associated factor 1 (EAF1).	[11]

References

• [1] ELL and EAF1 are Cajal body components that are disrupted in MLL-ELL leukemia.Mol Biol Cell. 2003 Apr;14(4):1517-28. doi: 10.1091/mbc.e02-07-0394.
• [2] Conditional Deletion of Eaf1 Induces Murine Prostatic Intraepithelial Neoplasia in Mice.Neoplasia. 2019 Aug;21(8):752-764. doi: 10.1016/j.neo.2019.05.005. Epub 2019 Jun 21.
• [3] Physical and Functional Interactions between ELL2 and RB in the Suppression of Prostate Cancer Cell Proliferation, Migration, and Invasion.Neoplasia. 2017 Mar;19(3):207-215. doi: 10.1016/j.neo.2017.01.001. Epub 2017 Feb 3.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.