Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8BSRPC)

DOT Name Rho GTPase-activating protein 27 (ARHGAP27)
Synonyms CIN85-associated multi-domain-containing Rho GTPase-activating protein 1; Rho-type GTPase-activating protein 27; SH3 domain-containing protein 20
Gene Name ARHGAP27
Related Disease
Neoplasm ( )
Anxiety ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
UniProt ID
RHG27_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3PP2
Pfam ID
PF00169 ; PF00620 ; PF00397
Sequence
MAADVVGDVYVLVEHPFEYTGKDGRRVAIRPNERYRLLRRSTEHWWHVRREPGGRPFYLP
AQYVRELPALGNPAAAAPPGPHPSPAAPEPLAYDYRFVSAAATAGPDGAPEESGGRASSL
CGPAQRGAATQRSSLAPGLPACLYLRPAAPVRPAQSLNDLACAAVSPPAGLLGSSGSFKA
CSVAGSWVCPRPLARSDSENVYEVIQDLHVPPPEESAEQVDDPPEPVYANIERQPRATSP
GAAAAPLPSPVWETHTDAGTGRPYYYNPDTGVTTWESPFEAAEGAASPATSPASVDSHVS
LETEWGQYWDEESRRVFFYNPLTGETAWEDEAENEPEEELEMQPGLSPGSPGDPRPPTPE
TDYPESLTSYPEEDYSPVGSFGEPGPTSPLTTPPGWSCHVSQDKQMLYTNHFTQEQWVRL
EDPHGKPYFYNPEDSSVRWELPQVPVPAPRSIHKSSQDGDTPAQASPPEEKVPAELDEVG
SWEEVSPATAAVRTKTLDKAGVLHRTKTADKGKRLRKKHWSASWTVLEGGVLTFFKDSKT
SAAGGLRQPSKFSTPEYTVELRGATLSWAPKDKSSRKNVLELRSRDGSEYLIQHDSEAII
STWHKAIAQGIQELSAELPPEESESSRVDFGSSERLGSWQEKEEDARPNAAAPALGPVGL
ESDLSKVRHKLRKFLQRRPTLQSLREKGYIKDQVFGCALAALCERERSRVPRFVQQCIRA
VEARGLDIDGLYRISGNLATIQKLRYKVDHDERLDLDDGRWEDVHVITGALKLFFRELPE
PLFPFSHFRQFIAAIKLQDQARRSRCVRDLVRSLPAPNHDTLRMLFQHLCRVIEHGEQNR
MSVQSVAIVFGPTLLRPEVEETSMPMTMVFQNQVVELILQQCADIFPPH
Function
Rho GTPase-activating protein which may be involved in clathrin-mediated endocytosis. GTPase activators for the Rho-type GTPases act by converting them to an inactive GDP-bound state. Has activity toward CDC42 and RAC1.
Tissue Specificity Expressed in germinal center B-cell, spleen, chronic lymphocytic leukemia, pancreatic cancer and lung cancer.
Reactome Pathway
RAC1 GTPase cycle (R-HSA-9013149 )
CDC42 GTPase cycle (R-HSA-9013148 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Biomarker [1]
Anxiety DISIJDBA Strong Genetic Variation [2]
Breast carcinoma DIS2UE88 Strong Genetic Variation [3]
Epithelial ovarian cancer DIS56MH2 Limited Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Rho GTPase-activating protein 27 (ARHGAP27). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Rho GTPase-activating protein 27 (ARHGAP27). [11]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [6]
Quercetin DM3NC4M Approved Quercetin increases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [7]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [8]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [9]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [10]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [12]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [13]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Rho GTPase-activating protein 27 (ARHGAP27). [14]
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⏷ Show the Full List of 8 Drug(s)

References

1 Enhanced cell growth and tumorigenicity of rat glioma cells by stable expression of human CD133 through multiple molecular actions.Glia. 2013 Sep;61(9):1402-17. doi: 10.1002/glia.22521. Epub 2013 Jul 6.
2 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
3 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
4 Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.Nat Commun. 2013;4:1627. doi: 10.1038/ncomms2613.
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 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
7 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
8 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.
9 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
10 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
11 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.
12 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.
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 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.