Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2BMEAE)

• DOT Name: Early estrogen-induced gene 1 protein (EEIG1)
• Synonyms: EEIG1
• Gene Name: EEIG1
• UniProt ID: EEIG1_HUMAN
• Pfam ID: PF10358
• Sequence:
  MAFLMKKKKFKFQTTFTLEELTAVPFVNGVLFCKVRLLDGGDFVSLSSREEVQENCVRWR
  KRFTFVCKMSANPATGLLDPCVFRVSVRKELKGGKAYSKLGFADLNLAEFAGSGSTVRCC
  LLEGYDTKNTRQDNSILKVTIGMFLLSGDPCFKTPPSTAKSISIPGQDSSLQLTCKGGGT
  SSGGSSTNSLTGSRPPKARPTILSSGLPEEPDQNLSSPEEVFHSGHSRNSSYASQQSKIS
  GYSTEHSRSSSLSDLTHRRNTSTSSSASGGLGMTVEGPEGSEREHRPPEKPPRPPRPLHL
  SDRSFRRKKDSVESHPTWVDDTRIDADAIVEKIVQSQDFTDGSNTEDSNLRLFVSRDGSA
  TLSGIQLATRVSSGVYEPVVIESH
• Function: Key component of TNFSF11/RANKL- and TNF-induced osteoclastogenesis pathways, thereby mediates bone resorption in pathological bone loss conditions. Required for TNFSF11/RANKL-induced osteoclastogenesis via its interaction with TNFRSF11A/RANK, thereby facilitates the downsteam transcription of NFATC1 and activation of PLCG2. Facilitates recruitment of the transcriptional repressor PRDM1/BLIMP1 to the promoter of the anti-osteoclastogenesis gene IRF8, thereby resulting in transcription of osteoclast differentiation factors. May play a role in estrogen action.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Early estrogen-induced gene 1 protein (EEIG1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Early estrogen-induced gene 1 protein (EEIG1).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Early estrogen-induced gene 1 protein (EEIG1).	[13]

19 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 Early estrogen-induced gene 1 protein (EEIG1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[6]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Early estrogen-induced gene 1 protein (EEIG1).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[8]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[9]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[5]
Estriol	DMOEM2I	Approved	Estriol increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[15]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[16]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[17]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol increases the expression of Early estrogen-induced gene 1 protein (EEIG1).	[5]

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] 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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1. Mol Endocrinol. 2004 Feb;18(2):402-11. doi: 10.1210/me.2003-0202. Epub 2003 Nov 6.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [13] 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.
• [14] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [17] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.