Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV3MRFE)

• DOT Name: CDC42 small effector protein 1 (CDC42SE1)
• Synonyms: CDC42-binding protein SCIP1; Small effector of CDC42 protein 1
• Gene Name: CDC42SE1
• Related Disease: Skin cancer
• UniProt ID: C42S1_HUMAN
• Sequence:
  MSEFWHKLGCCVVEKPQPKKKRRRIDRTMIGEPMNFVHLTHIGSGEMGAGDGLAMTGAVQ
  EQMRSKGNRDRPWSNSRGL
• Function: Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly. Alters CDC42-induced cell shape changes. In activated T-cells, may play a role in CDC42-mediated F-actin accumulation at the immunological synapse. May play a role in early contractile events in phagocytosis in macrophages.
• Tissue Specificity: Widely expressed. Expressed at higher level in T-lymphocytes, dendritic and whole blood cells.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Skin cancer	DISTM18U	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 small effector protein 1 (CDC42SE1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CDC42 small effector protein 1 (CDC42SE1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CDC42 small effector protein 1 (CDC42SE1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of CDC42 small effector protein 1 (CDC42SE1).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of CDC42 small effector protein 1 (CDC42SE1).	[6]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of CDC42 small effector protein 1 (CDC42SE1).	[7]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of CDC42 small effector protein 1 (CDC42SE1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CDC42 small effector protein 1 (CDC42SE1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CDC42 small effector protein 1 (CDC42SE1).	[11]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of CDC42 small effector protein 1 (CDC42SE1).	[12]

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 affects the methylation of CDC42 small effector protein 1 (CDC42SE1).	[9]

References

• [1] Overexpression of CDC42SE1 in A431 Cells Reduced Cell Proliferation by Inhibiting the Akt Pathway.Cells. 2019 Feb 2;8(2):117. doi: 10.3390/cells8020117.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [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] 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.