Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBM9BHT)

• DOT Name: ETS domain-containing protein Elk-3 (ELK3)
• Synonyms: ETS-related protein ERP; ETS-related protein NET; Serum response factor accessory protein 2; SAP-2; SRF accessory protein 2
• Gene Name: ELK3
• UniProt ID: ELK3_HUMAN
• Pfam ID: PF00178
• Sequence:
  MESAITLWQFLLQLLLDQKHEHLICWTSNDGEFKLLKAEEVAKLWGLRKNKTNMNYDKLS
  RALRYYYDKNIIKKVIGQKFVYKFVSFPEILKMDPHAVEISRESLLLQDSDCKASPEGRE
  AHKHGLAALRSTSRNEYIHSGLYSSFTINSLQNPPDAFKAIKTEKLEEPPEDSPPVEEVR
  TVIRFVTNKTDKHVTRPVVSLPSTSEAAAASAFLASSVSAKISSLMLPNAASISSASPFS
  SRSPSLSPNSPLPSEHRSLFLEAACHDSDSLEPLNLSSGSKTKSPSLPPKAKKPKGLEIS
  APPLVLSGTDIGSIALNSPALPSGSLTPAFFTAQTPNGLLLTPSPLLSSIHFWSSLSPVA
  PLSPARLQGPSTLFQFPTLLNGHMPVPIPSLDRAASPVLLSSNSQKS
• Function: May be a negative regulator of transcription, but can activate transcription when coexpressed with Ras, Src or Mos. Forms a ternary complex with the serum response factor and the ETS and SRF motifs of the Fos serum response element.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	ETS domain-containing protein Elk-3 (ELK3) affects the response to substance of Mitomycin.	[15]

16 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 ETS domain-containing protein Elk-3 (ELK3).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ETS domain-containing protein Elk-3 (ELK3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ETS domain-containing protein Elk-3 (ELK3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of ETS domain-containing protein Elk-3 (ELK3).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ETS domain-containing protein Elk-3 (ELK3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ETS domain-containing protein Elk-3 (ELK3).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ETS domain-containing protein Elk-3 (ELK3).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of ETS domain-containing protein Elk-3 (ELK3).	[13]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of ETS domain-containing protein Elk-3 (ELK3).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [14] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [15] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.