Details of Drug Off-Target (DOT)

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

• DOT Name: Interactor protein for cytohesin exchange factors 1 (IPCEF1)
• Synonyms: Phosphoinositide-binding protein PIP3-E
• Gene Name: IPCEF1
• Related Disease:
  Allergic contact dermatitis
  Diabetic kidney disease
  Lymphoid leukemia
  Small lymphocytic lymphoma
• UniProt ID: ICEF1_HUMAN
• PDB ID: 5MR1
• Pfam ID: PF00169
• Sequence:
  MTSYMAIDGSALVPLRQKPRRKTQGFLTMSRRRISCKDLGHADCQGWLYKKKEKGSFLSN
  KWKKFWVILKGSSLYWYSNQMAEKADGFVNLPDFTVERASECKKKHAFKISHPQIKTFYF
  AAENVQEMNVWLNKLGSAVIHQESTTKDEECYSESEQEDPEIAAETPPPPHASQTQSLTA
  QQASSSSPSLSGTSYSFSSLENTVKTPSSFPSSLSKERQSLPDTVNSLSAAEDEGQPITF
  AVQVHSPVPSEAGIHKALENSFVTSESGFLNSLSSDDTSSLSSNHDHLTVPDKPAGSKIM
  DKEETKVSEDDEMEKLYKSLEQASLSPLGDRRPSTKKELRKSFVKRCKNPSINEKLHKIR
  TLNSTLKCKEHDLAMINQLLDDPKLTARKYREWKVMNTLLIQDIYQQQRASPAPDDTDDT
  PQELKKSPSSPSVENSI
• Function: Enhances the promotion of guanine-nucleotide exchange by PSCD2 on ARF6 in a concentration-dependent manner.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic contact dermatitis	DISFFVF9	Definitive	Biomarker	[1]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[2]
Lymphoid leukemia	DIS65TYQ	Strong	Biomarker	[3]
Small lymphocytic lymphoma	DIS30POX	Disputed	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[6]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[1]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[10]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[1]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[6]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[12]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[13]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[14]

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 affects the methylation of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Interactor protein for cytohesin exchange factors 1 (IPCEF1).	[11]

References

• [1] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [2] Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).PLoS Genet. 2015 Aug 25;11(8):e1005352. doi: 10.1371/journal.pgen.1005352. eCollection 2015 Aug.
• [3] A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.Nat Genet. 2014 Jan;46(1):56-60. doi: 10.1038/ng.2843. Epub 2013 Dec 1.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [7] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [10] 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.
• [11] 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.
• [12] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [13] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [14] Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: In vitro testing in human liver cells. Toxicol In Vitro. 2020 Dec;69:105001. doi: 10.1016/j.tiv.2020.105001. Epub 2020 Sep 15.