Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX3YDPN)

• DOT Name: Cdc42 effector protein 2 (CDC42EP2)
• Synonyms: Binder of Rho GTPases 1
• Gene Name: CDC42EP2
• UniProt ID: BORG1_HUMAN
• Pfam ID: PF14957 ; PF00786
• Sequence:
  MSTKVPIYLKRGSRKGKKEKLRDLLSSDMISPPLGDFRHTIHIGSGGGSDMFGDISFLQG
  KFHLLPGTMVEGPEEDGTFDLPFQFTRTATVCGRELPDGPSPLLKNAISLPVIGGPQALT
  LPTAQAPPKPPRLHLETPQPSPQEGGSVDIWRIPETGSPNSGLTPESGAEEPFLSNASSL
  LSLHVDLGPSILDDVLQIMDQDLDSMQIPT
• Function: Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation in fibroblasts in a CDC42-dependent manner.
• Tissue Specificity: Highly expressed in the heart. Weakly expressed in the pancreas and liver.
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  RHOQ GTPase cycle (R-HSA-9013406)
  MAPK6/MAPK4 signaling (R-HSA-5687128)

Molecular Interaction Atlas (MIA) of This DOT

14 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 Cdc42 effector protein 2 (CDC42EP2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cdc42 effector protein 2 (CDC42EP2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cdc42 effector protein 2 (CDC42EP2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cdc42 effector protein 2 (CDC42EP2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cdc42 effector protein 2 (CDC42EP2).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cdc42 effector protein 2 (CDC42EP2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cdc42 effector protein 2 (CDC42EP2).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cdc42 effector protein 2 (CDC42EP2).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cdc42 effector protein 2 (CDC42EP2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cdc42 effector protein 2 (CDC42EP2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cdc42 effector protein 2 (CDC42EP2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Cdc42 effector protein 2 (CDC42EP2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cdc42 effector protein 2 (CDC42EP2).	[14]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Cdc42 effector protein 2 (CDC42EP2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cdc42 effector protein 2 (CDC42EP2).	[11]

References

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• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [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] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.