Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTINOJJ7)

DOT Name Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1)
Synonyms Centaurin-delta-2; Cnt-d2
Gene Name ARAP1
Related Disease
Diabetic kidney disease ( )
Type-1/2 diabetes ( )
leukaemia ( )
Leukemia ( )
Malignant soft tissue neoplasm ( )
Sarcoma ( )
Sickle-cell anaemia ( )
Non-insulin dependent diabetes ( )
Serous cystadenocarcinoma ( )
UniProt ID
ARAP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4X1V
Pfam ID
PF01412 ; PF00169 ; PF00788 ; PF00620 ; PF00536
Sequence
MAEAGDAALSVAEWLRALHLEQYTGLFEQHGLVWATECQGLSDTRLMDMGMLLPGHRRRI
LAGLLRAHTSPAPAPRPTPRPVPMKRHIFRSPPVPATPPEPLPTTTEDEGLPAAPPIPPR
RSCLPPTCFTTPSTAAPDPVLPPLPAKRHLAELSVPPVPPRTGPPRLLVSLPTKEEESLL
PSLSSPPQPQSEEPLSTLPQGPPQPPSPPPCPPEIPPKPVRLFPEFDDSDYDEVPEEGPG
APARVMTKKEEPPPSRVPRAVRVASLLSEGEELSGDDQGDEEEDDHAYEGVPNGGWHTSS
LSLSLPSTIAAPHPMDGPPGGSTPVTPVIKAGWLDKNPPQGSYIYQKRWVRLDTDHLRYF
DSNKDAYSKRFISVACISHVAAIGDQKFEVITNNRTFAFRAESDVERKEWMQALQQAMAE
QRARARLSSAYLLGVPGSEQPDRAGSLELRGFKNKLYVAVVGDKVQLYKNLEEYHLGIGI
TFIDMSVGNVKEVDRRSFDLTTPYRIFSFSADSELEKEQWLEAMQGAIAEALSTSEVAER
IWAAAPNRFCADCGAPQPDWASINLCVVICKRCAGEHRGLGAGVSKVRSLKMDRKVWTET
LIELFLQLGNGAGNRFWAANVPPSEALQPSSSPSTRRCHLEAKYREGKYRRYHPLFGNQE
ELDKALCAAVTTTDLAETQALLGCGAGINCFSGDPEAPTPLALAEQAGQTLQMEFLRNNR
TTEVPRLDSMKPLEKHYSVVLPTVSHSGFLYKTASAGKLLQDRRAREEFSRRWCVLGDGV
LSYFENERAVTPNGEIRASEIVCLAVPPPDTHGFEHTFEVYTEGERLYLFGLESAEQAHE
WVKCIAKAFVPPLAEDLLARDFERLGRLPYKAGLSLQRAQEGWFSLSGSELRAVFPEGPC
EEPLQLRKLQELSIQGDSENQVLVLVERRRTLYIQGERRLDFMGWLGAIQKAAASMGDTL
SEQQLGDSDIPVIVYRCVDYITQCGLTSEGIYRKCGQTSKTQRLLESLRQDARSVHLKEG
EQHVDDVSSALKRFLRDLPDGLFTRAQRLTWLEASEIEDEEEKVSRYRELLVRLPPVNRA
TVKALISHLYCVQCFSDTNQMNVHNLAIVFGPTLFQTDGQDYKAGRVVEDLINHYVVVFS
VDEEELRKQREEITAIVKMRVAGTASGTQHAGDFICTVYLEEKKAETEQHIKVPASMTAE
ELTLEILDRRNVGIREKDYWTCFEVNEREEAERPLHFAEKVLPILHGLGTDSHLVVKKHQ
AMEAMLLYLASRVGDTKHGMMKFREDRSLLGLGLPSGGFHDRYFILNSSCLRLYKEVRSQ
RPWSGAPETSHRPEKEWPIKSLKVYLGVKKKLRPPTCWGFTVVHETEKHEKQQWYLCCDT
QMELREWFATFLFVQHDGLVWPSEPSRVSRAVPEVRLGSVSLIPLRGSENEMRRSVAAFT
ADPLSLLRNV
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. Has a preference for ARF1 and ARF5.
Tissue Specificity
Detected in heart, skeletal muscle, spleen, kidney, liver, placenta, lung, peripheral blood leukocytes, adrenal gland, bone marrow, brain, lymph node, mammary gland, prostate, spinal cord, stomach, thyroid and trachea.
KEGG Pathway
Endocytosis (hsa04144 )
Reactome Pathway
RHOA GTPase cycle (R-HSA-8980692 )
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 (R-HSA-8849469 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Diabetic kidney disease DISJMWEY Definitive Biomarker [1]
Type-1/2 diabetes DISIUHAP Definitive Biomarker [1]
leukaemia DISS7D1V Strong Altered Expression [2]
Leukemia DISNAKFL Strong Altered Expression [2]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [2]
Sarcoma DISZDG3U Strong Biomarker [2]
Sickle-cell anaemia DIS5YNZB Strong Genetic Variation [3]
Non-insulin dependent diabetes DISK1O5Z moderate Genetic Variation [4]
Serous cystadenocarcinoma DISVK716 moderate Biomarker [5]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [6]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [7]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [16]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [18]
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10 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 Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [9]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [10]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [11]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [13]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [14]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [15]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1). [20]
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⏷ Show the Full List of 10 Drug(s)

References

1 Analysis of circulating lncRNA expression profiles in patients with diabetes mellitus and diabetic nephropathy: Differential expression profile of circulating lncRNA?"Yang Y. Fan Q
2 Expression profiles of signal transduction genes in ex vivo drug-resistant pediatric acute lymphoblastic leukemia.Anticancer Res. 2012 Feb;32(2):503-6.
3 A Genome-Wide Screen for Large-Effect Alloimmunization Susceptibility Loci among Red Blood Cell Transfusion Recipients with Sickle Cell Disease.Transfus Med Hemother. 2014 Nov;41(6):453-61. doi: 10.1159/000369079. Epub 2014 Nov 7.
4 Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.
5 ARAP1 is an independent prognostic biomarker in older women with ovarian high-grade serous adenocarcinoma receiving first-line platinum-based antineoplastic therapy.Acta Oncol. 2020 Jan;59(1):40-47. doi: 10.1080/0284186X.2019.1657941. Epub 2019 Sep 3.
6 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.
7 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
8 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.
9 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.
10 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 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.
12 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
13 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.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 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.
16 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.
17 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.
18 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.
19 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
20 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.