Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8SG9I1)

• DOT Name: CDC42 small effector protein 2 (CDC42SE2)
• Synonyms: Small effector of CDC42 protein 2
• Gene Name: CDC42SE2
• Related Disease:
  Alzheimer disease
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Endometrium adenocarcinoma
  Malignant uterine tumour
  Uterine serous carcinoma
  Crohn disease
  Inflammatory bowel disease
  Schizophrenia
• UniProt ID: C42S2_HUMAN
• Pfam ID: PF00786
• Sequence:
  MSEFWLCFNCCIAEQPQPKRRRRIDRSMIGEPTNFVHTAHVGSGDLFSGMNSVSSIQNQM
  QSKGGYGGGMPANVQMQLVDTKAG
• 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. Highly expressed in CCRF-CEM T-lymphocytes, Jurkat T-lymphocytes, and Raji B-lymphocytes compared (at protein level).
• Reactome Pathway: CDC42 GTPase cycle (R-HSA-9013148)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[3]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[3]
Endometrium adenocarcinoma	DISY6744	Strong	Biomarker	[4]
Malignant uterine tumour	DIS3QDT8	Strong	Biomarker	[5]
Uterine serous carcinoma	DISAW5MD	Strong	Biomarker	[4]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[6]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[6]
Schizophrenia	DISSRV2N	moderate	Genetic Variation	[7]

7 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 small effector protein 2 (CDC42SE2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CDC42 small effector protein 2 (CDC42SE2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CDC42 small effector protein 2 (CDC42SE2).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of CDC42 small effector protein 2 (CDC42SE2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of CDC42 small effector protein 2 (CDC42SE2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CDC42 small effector protein 2 (CDC42SE2).	[13]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of CDC42 small effector protein 2 (CDC42SE2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of CDC42 small effector protein 2 (CDC42SE2).	[14]

References

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• [2] Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese.Oncotarget. 2015 Nov 24;6(37):40327-36. doi: 10.18632/oncotarget.5530.
• [3] Culture characters, genetic background, estrogen/progesterone receptor expression, and tumorigenic activities of frequently used sixteen endometrial cancer cell lines.Clin Chim Acta. 2019 Feb;489:225-232. doi: 10.1016/j.cca.2018.08.013. Epub 2018 Aug 11.
• [4] Adenovirus-mediated expression of p53 or p21 in a papillary serous endometrial carcinoma cell line (SPEC-2) results in both growth inhibition and apoptotic cell death: potential application of gene therapy to endometrial cancer.Clin Cancer Res. 2000 Jan;6(1):278-84.
• [5] Biologic effects of platelet-derived growth factor receptor blockade in uterine cancer.Clin Cancer Res. 2014 May 15;20(10):2740-50. doi: 10.1158/1078-0432.CCR-13-2507. Epub 2014 Mar 14.
• [6] Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.Nat Genet. 2015 Sep;47(9):979-986. doi: 10.1038/ng.3359. Epub 2015 Jul 20.
• [7] ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure.PLoS One. 2011;6(12):e28790. doi: 10.1371/journal.pone.0028790. Epub 2011 Dec 20.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] 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.
• [14] 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.
• [15] Comparative analysis of AhR-mediated TCDD-elicited gene expression in human liver adult stem cells. Toxicol Sci. 2009 Nov;112(1):229-44.