Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT525WA)

• DOT Name: Cdc42 effector protein 1 (CDC42EP1)
• Synonyms: Binder of Rho GTPases 5; Serum protein MSE55
• Gene Name: CDC42EP1
• Related Disease:
  Chromosomal disorder
  Lymphatic malformation 1
  Peeling skin syndrome 1
  Potocki-Shaffer syndrome
  Systemic sclerosis
  Autoimmune disease
  Osteoarthritis
  AIDS-related lymphoma
  Arthritis
• UniProt ID: BORG5_HUMAN
• Pfam ID: PF14957 ; PF00786
• Sequence:
  MPGPQGGRGAATMSLGKLSPVGWVSSSQGKRRLTADMISHPLGDFRHTMHVGRGGDVFGD
  TSFLSNHGGSSGSTHRSPRSFLAKKLQLVRRVGAPPRRMASPPAPSPAPPAISPIIKNAI
  SLPQLNQAAYDSLVVGKLSFDSSPTSSTDGHSSYGLDSGFCTISRLPRSEKPHDRDRDGS
  FPSEPGLRRSDSLLSFRLDLDLGPSLLSELLGVMSLPEAPAAETPAPAANPPAPTANPTG
  PAANPPATTANPPAPAANPSAPAATPTGPAANPPAPAASSTPHGHCPNGVTAGLGPVAEV
  KSSPVGGGPRGPAGPALGRHWGAGWDGGHHYPEMDARQERVEVLPQARASWESLDEEWRA
  PQAGSRTPVPSTVQANTFEFADAEEDDEVKV
• Function: Probably involved in the organization of the actin cytoskeleton. Induced membrane extensions in fibroblasts.
• Tissue Specificity: Endothelial and bone marrow stromal cells.
• Reactome Pathway:
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOJ GTPase cycle (R-HSA-9013409)
  RAC3 GTPase cycle (R-HSA-9013423)
  CDC42 GTPase cycle (R-HSA-9013148)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chromosomal disorder	DISM5BB5	Definitive	Genetic Variation	[1]
Lymphatic malformation 1	DIS857QZ	Definitive	Genetic Variation	[1]
Peeling skin syndrome 1	DIS35574	Definitive	Biomarker	[2]
Potocki-Shaffer syndrome	DISKGU59	Definitive	Biomarker	[2]
Systemic sclerosis	DISF44L6	Definitive	Biomarker	[2]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[3]
Osteoarthritis	DIS05URM	Strong	Biomarker	[4]
AIDS-related lymphoma	DISSLRAU	Limited	Biomarker	[5]
Arthritis	DIST1YEL	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Cdc42 effector protein 1 (CDC42EP1) affects the response to substance of Fluorouracil.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cdc42 effector protein 1 (CDC42EP1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cdc42 effector protein 1 (CDC42EP1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[13]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[14]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[15]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[16]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Cdc42 effector protein 1 (CDC42EP1).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cdc42 effector protein 1 (CDC42EP1).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cdc42 effector protein 1 (CDC42EP1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cdc42 effector protein 1 (CDC42EP1).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Cdc42 effector protein 1 (CDC42EP1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cdc42 effector protein 1 (CDC42EP1).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cdc42 effector protein 1 (CDC42EP1).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Cdc42 effector protein 1 (CDC42EP1).	[12]

References

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• [2] Antibodies against citrullinated alpha enolase peptides in primary Sjogren's syndrome.Clin Immunol. 2017 Oct;183:300-303. doi: 10.1016/j.clim.2017.09.012. Epub 2017 Sep 14.
• [3] Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis.Immunol Rev. 2010 Jan;233(1):34-54. doi: 10.1111/j.0105-2896.2009.00850.x.
• [4] Association of Distinct Fine Specificities of Anti-Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis.Arthritis Rheumatol. 2017 Dec;69(12):2303-2313. doi: 10.1002/art.40227. Epub 2017 Oct 30.
• [5] Biscoclaurine alkaloid cepharanthine inhibits the growth of primary effusion lymphoma in vitro and in vivo and induces apoptosis via suppression of the NF-kappaB pathway.Int J Cancer. 2009 Sep 15;125(6):1464-72. doi: 10.1002/ijc.24521.
• [6] Immunization with Porphyromonas gingivalis enolase induces autoimmunity to mammalian -enolase and arthritis in DR4-IE-transgenic mice.Arthritis Rheum. 2011 Dec;63(12):3818-23. doi: 10.1002/art.30639.
• [7] 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.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] 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.
• [13] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [16] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [17] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.