Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX0U8PX)

DOT Name Rho guanine nucleotide exchange factor 26 (ARHGEF26)
Synonyms SH3 domain-containing guanine exchange factor
Gene Name ARHGEF26
Related Disease
Adult glioblastoma ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Coronary heart disease ( )
Glioblastoma multiforme ( )
Glioma ( )
Neoplasm ( )
Schizophrenia ( )
UniProt ID
ARHGQ_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6MYE; 7YKG
Pfam ID
PF00169 ; PF00621 ; PF00018
Sequence
MDGESEVDFSSNSITPLWRRRSIPQPHQVLGRSKPRPQSYQSPNGLLITDFPVEDGGTLL
AAQIPAQVPTASDSRTVHRSPLLLGAQRRAVANGGTASPEYRAASPRLRRPKSPKLPKAV
PGGSPKSPANGAVTLPAPPPPPVLRPPRTPNAPAPCTPEEDLTGLTASPVPSPTANGLAA
NNDSPGSGSQSGRKAKDPERGLFPGPQKSSSEQKLPLQRLPSQENELLENPSVVLSTNSP
AALKVGKQQIIPKSLASEIKISKSNNQNVEPHKRLLKVRSMVEGLGGPLGHAGEESEVDN
DVDSPGSLRRGLRSTSYRRAVVSGFDFDSPTSSKKKNRMSQPVLKVVMEDKEKFSSLGRI
KKKMLKGQGTFDGEENAVLYQNYKEKALDIDSDEESEPKEQKSDEKIVIHHKPLRSTWSQ
LSAVKRKGLSQTVSQEERKRQEAIFEVISSEHSYLLSLEILIRMFKNSKELSDTMTKTER
HHLFSNITDVCEASKKFFIELEARHQNNIFIDDISDIVEKHTASTFDPYVKYCTNEVYQQ
RTLQKLLATNPSFKEVLSRIESHEDCRNLPMISFLILPMQRVTRLPLLMDTICQKTPKDS
PKYEVCKRALKEVSKLVRLCNEGARKMERTEMMYTINSQLEFKIKPFPLVSSSRWLVKRG
ELTAYVEDTVLFSRRTSKQQVYFFLFNDVLIITKKKSEESYNVNDYSLRDQLLVESCDNE
ELNSSPGKNSSTMLYSRQSSASHLFTLTVLSNHANEKVEMLLGAETQSERARWITALGHS
SGKPPADRTSLTQVEIVRSFTAKQPDELSLQVADVVLIYQRVSDGWYEGERLRDGERGWF
PMECAKEITCQATIDKNVERMGRLLGLETNV
Function
Activates RhoG GTPase by promoting the exchange of GDP by GTP. Required for the formation of membrane ruffles during macropinocytosis. Required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB, which induces cytoskeleton rearrangements and promotes bacterial entry.
Tissue Specificity Isoform 1 is broadly expressed, with highest levels in liver (at protein level). Certain mRNA species appear to be specifically expressed in prostate and liver.
KEGG Pathway
Bacterial invasion of epithelial cells (hsa05100 )
Salmonella infection (hsa05132 )
Reactome Pathway
G alpha (12/13) signalling events (R-HSA-416482 )
CDC42 GTPase cycle (R-HSA-9013148 )
RHOG GTPase cycle (R-HSA-9013408 )
NRAGE signals death through JNK (R-HSA-193648 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Altered Expression [1]
Arteriosclerosis DISK5QGC Strong Biomarker [2]
Atherosclerosis DISMN9J3 Strong Biomarker [2]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [3]
Glioblastoma multiforme DISK8246 Strong Altered Expression [1]
Glioma DIS5RPEH Strong Biomarker [1]
Neoplasm DISZKGEW Strong Biomarker [1]
Schizophrenia DISSRV2N Limited Genetic Variation [4]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [5]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [14]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [16]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [7]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [8]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [10]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [12]
Amphotericin B DMTAJQE Approved Amphotericin B increases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [8]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide increases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [8]
Gentamicin DMKINJO Approved Gentamicin increases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [8]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [13]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [17]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Rho guanine nucleotide exchange factor 26 (ARHGEF26). [18]
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⏷ Show the Full List of 13 Drug(s)

References

1 SGEF Is Regulated via TWEAK/Fn14/NF-B Signaling and Promotes Survival by Modulation of the DNA Repair Response to Temozolomide.Mol Cancer Res. 2016 Mar;14(3):302-12. doi: 10.1158/1541-7786.MCR-15-0183. Epub 2016 Jan 13.
2 The guanine-nucleotide exchange factor SGEF plays a crucial role in the formation of atherosclerosis.PLoS One. 2013;8(1):e55202. doi: 10.1371/journal.pone.0055202. Epub 2013 Jan 25.
3 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
4 Genome-wide association study of schizophrenia in Ashkenazi Jews.Am J Med Genet B Neuropsychiatr Genet. 2015 Dec;168(8):649-59. doi: 10.1002/ajmg.b.32349. Epub 2015 Jul 21.
5 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.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2010 Oct 15;401(2):245-50. doi: 10.1016/j.bbrc.2010.09.039. Epub 2010 Sep 16.
9 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
10 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
13 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.
14 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.
15 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.
16 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.
17 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
18 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.