Details of Drug Off-Target (DOT)

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

• DOT Name: Cdc42 effector protein 5 (CDC42EP5)
• Synonyms: Binder of Rho GTPases 3
• Gene Name: CDC42EP5
• Related Disease: Allergic rhinitis
• UniProt ID: BORG3_HUMAN
• Pfam ID: PF14957 ; PF00786
• Sequence:
  MPVLKQLGPAQPKKRPDRGALSISAPLGDFRHTLHVGRGGDAFGDTSFLSRHGGGPPPEP
  RAPPAGAPRSPPPPAVPQSAAPSPADPLLSFHLDLGPSMLDAVLGVMDAARPEAAAAKPD
  AEPRPGTQPPQARCRPNADLELNDVIGL
• 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. Inhibits MAPK8 independently of CDC42 binding. Controls septin organization and this effect is negatively regulated by CDC42.
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  MAPK6/MAPK4 signaling (R-HSA-5687128)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[1]

10 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 5 (CDC42EP5).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Cdc42 effector protein 5 (CDC42EP5).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cdc42 effector protein 5 (CDC42EP5).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cdc42 effector protein 5 (CDC42EP5).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cdc42 effector protein 5 (CDC42EP5).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cdc42 effector protein 5 (CDC42EP5).	[6]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cdc42 effector protein 5 (CDC42EP5).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cdc42 effector protein 5 (CDC42EP5).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cdc42 effector protein 5 (CDC42EP5).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cdc42 effector protein 5 (CDC42EP5).	[11]

2 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 increases the methylation of Cdc42 effector protein 5 (CDC42EP5).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cdc42 effector protein 5 (CDC42EP5).	[10]

References

• [1] Exploring of the molecular mechanism of rhinitis via bioinformatics methods.Mol Med Rep. 2018 Feb;17(2):3014-3020. doi: 10.3892/mmr.2017.8213. Epub 2017 Dec 7.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] 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.
• [7] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [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.