Details of Drug Off-Target (DOT)

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

DOT Name Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2)
Synonyms Centaurin-delta-1; Cnt-d1; Protein PARX
Gene Name ARAP2
Related Disease
Alzheimer disease ( )
Amyotrophic lateral sclerosis ( )
Non-small-cell lung cancer ( )
UniProt ID
ARAP2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1X40; 2COD
Pfam ID
PF01412 ; PF00169 ; PF00788 ; PF00620 ; PF00536
Sequence
MSSVSEVNVDIKDFLMSINLEQYLLHFHESGFTTVKDCAAINDSLLQKIGISPTGHRRRI
LKQLQIILSKMQDIPIYANVHKTKKNDDPSKDYHVPSSDQNICIELSNSGSVQTSSPPQL
ETVRKNLEDSDASVERSQYPQSDDKLSPPKRDFPTAEEPHLNLGSLNDSLFGSDNIKIES
LITKKTVDHTVEEQQTEKVKLITENLSKLPNADSECLSFVGCSTSGTNSGNGTNGLLEGS
PPSPFFKFQGEMIVNDLYVPSSPILAPVRSRSKLVSRPSRSFLLRHRPVPEIPGSTKGVS
GSYFRERRNVATSTEKSVAWQNSNEENSSSIFPYGETFLFQRLENSKKRSIKNEFLTQGE
ALKGEAATATNSFIIKSSIYDNRKEKISEDKVEDIWIPREDKNNFLIDTASESEYSTVEE
CFQSLRRKNSKASKSRTQKALILDSVNRHSYPLSSTSGNADSSAVSSQAISPYACFYGAS
AKKVKSGWLDKLSPQGKRMFQKRWVKFDGLSISYYNNEKEMYSKGIIPLSAISTVRVQGD
NKFEVVTTQRTFVFRVEKEEERNDWISILLNALKSQSLTSQSQAVVTPEKCGYLELRGYK
AKIFTVLSGNSVWLCKNEQDFKSGLGITIIPMNVANVKQVDRTVKQSFEIITPYRSFSFT
AETEKEKQDWIEAVQQSIAETLSDYEVAEKIWFNESNRSCADCKAPDPDWASINLCVVIC
KKCAGQHRSLGPKDSKVRSLKMDASIWSNELIELFIVIGNKRANDFWAGNLQKDEELHMD
SPVEKRKNFITQKYKEGKFRKTLLASLTKEELNKALCAAVVKPDVLETMALLFSGADVMC
ATGDPVHSTPYLLAKKAGQSLQMEFLYHNKFSDFPQHDIHSEGVLSQESSQSTFLCDFLY
QAPSAASKLSSEKKLLEETNKKWCVLEGGFLSYYENDKSTTPNGTININEVICLAIHKED
FYLNTGPIFIFEIYLPSERVFLFGAETSQAQRKWTEAIAKHFVPLFAENLTEADYDLIGQ
LFYKDCHALDQWRKGWFAMDKSSLHFCLQMQEVQGDRMHLRRLQELTISTMVQNGEKLDV
LLLVEKGRTLYIHGHTKLDFTVWHTAIEKAAGTDGNALQDQQLSKNDVPIIVNSCIAFVT
QYGLGCKYIYQKNGDPLHISELLESFKKDARSFKLRAGKHQLEDVTAVLKSFLSDIDDAL
LTKELYPYWISALDTQDDKERIKKYGAFIRSLPGVNRATLAAIIEHLYRVQKCSEINHMN
AHNLALVFSSCLFQTKGQTSEEVNVIEDLINNYVEIFEVKEDQVKQMDIENSFITKWKDT
QVSQAGDLLIEVYVERKEPDCSIIIRISPVMEAEELTNDILAIKNIIPTKGDIWATFEVI
ENEELERPLHYKENVLEQVLRWSSLAEPGSAYLVVKRFLTADTIKHCSDRSTLGSIKEGI
LKIKEEPSKILSGNKFQDRYFVLRDGFLFLYKDVKSSKHDKMFSLSSMKFYRGVKKKMKP
PTSWGLTAYSEKHHWHLCCDSSRTQTEWMTSIFIAQHEYDIWPPAGKERKRSITKNPKIG
GLPLIPIQHEGNATLARKNIESARAELERLRLSEKCDKESVDSSLKERASMVAHCLEHKD
DKLRNRPRKHRSFNCLEDTEPEAPLGQPKGHKGLKTLRKTEDRNSKATLDSDHKLPSRVI
EELNVVLQRSRTLPKELQDEQILK
Function
Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency.
Tissue Specificity Detected in brain, thymus, lymph node, thyroid, spinal cord, trachea, heart, skeletal muscle, spleen, kidney, liver, placenta, lung and peripheral blood leukocytes.
KEGG Pathway
Endocytosis (hsa04144 )
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
RAC3 GTPase cycle (R-HSA-9013423 )
RHOA GTPase cycle (R-HSA-8980692 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Genetic Variation [1]
Amyotrophic lateral sclerosis DISF7HVM Strong Genetic Variation [2]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [3]
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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 decreases the methylation of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [20]
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20 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [5]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [9]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [11]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [12]
Triclosan DMZUR4N Approved Triclosan increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [13]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [14]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [15]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [16]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [17]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [18]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [21]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [15]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [22]
QUERCITRIN DM1DH96 Investigative QUERCITRIN increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [23]
Nitrobenzanthrone DMN6L70 Investigative Nitrobenzanthrone decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 (ARAP2). [24]
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⏷ Show the Full List of 20 Drug(s)

References

1 Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.Alzheimers Dement. 2018 May;14(5):623-633. doi: 10.1016/j.jalz.2017.11.006. Epub 2017 Dec 20.
2 Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.Neurobiol Aging. 2013 Jan;34(1):357.e7-19. doi: 10.1016/j.neurobiolaging.2012.07.017. Epub 2012 Sep 5.
3 Cinnamtannin D1 from Rhododendron formosanum Induces Autophagy via the Inhibition of Akt/mTOR and Activation of ERK1/2 in Non-Small-Cell Lung Carcinoma Cells.J Agric Food Chem. 2015 Dec 9;63(48):10407-17. doi: 10.1021/acs.jafc.5b04375. Epub 2015 Nov 23.
4 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.
5 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
6 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.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 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.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
10 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
11 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
12 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
13 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
14 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
15 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
16 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
17 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
18 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
19 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.
20 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.
21 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.
22 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
23 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
24 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.