Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVX8835)

DOT Name Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1)
Synonyms AGAP-1; Centaurin-gamma-2; Cnt-g2; GTP-binding and GTPase-activating protein 1; GGAP1
Gene Name AGAP1
Related Disease
Intellectual disability ( )
Cardiovascular disease ( )
Craniofacial microsomia ( )
High blood pressure ( )
Knee osteoarthritis ( )
Parkinson disease ( )
Schizophrenia ( )
Autism ( )
UniProt ID
AGAP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7EB6
Pfam ID
PF12796 ; PF01412 ; PF00071
Sequence
MNYQQQLANSAAIRAEIQRFESVHPNIYSIYELLERVEEPVLQNQIREHVIAIEDAFVNS
QEWTLSRSVPELKVGIVGNLASGKSALVHRYLTGTYVQEESPEGGRFKKEIVVDGQSYLL
LIRDEGGPPEAQFAMWVDAVIFVFSLEDEISFQTVYHYYSRMANYRNTSEIPLVLVGTQD
AISSANPRVIDDARARKLSNDLKRCTYYETCATYGLNVERVFQDVAQKIVATRKKQQLSI
GPCKSLPNSPSHSSVCSAQVSAVHISQTSNGGGSLSDYSSSVPSTPSTSQKELRIDVPPT
ANTPTPVRKQSKRRSNLFTSRKGSDPDKEKKGLESRADSIGSGRAIPIKQGMLLKRSGKS
LNKEWKKKYVTLCDNGVLTYHPSLHDYMQNVHGKEIDLLRTTVKVPGKRPPRATSACAPI
SSPKTNGLSKDMSSLHISPNSGNVTSASGSQMASGISLVSFNSRPDGMHQRSYSVSSADQ
WSEATVIANSAISSDTGLGDSVCSSPSISSTTSPKLDPPPSPHANRKKHRRKKSTSNFKA
DGLSGTAEEQEENFEFIIVSLTGQTWHFEATTYEERDAWVQAIESQILASLQSCESSKNK
SRLTSQSEAMALQSIRNMRGNSHCVDCETQNPNWASLNLGALMCIECSGIHRNLGTHLSR
VRSLDLDDWPVELIKVMSSIGNELANSVWEESSQGRTKPSVDSTREEKERWIRAKYEQKL
FLAPLPCTELSLGQHLLRATADEDLRTAILLLAHGSRDEVNETCGEGDGRTALHLACRKG
NVVLAQLLIWYGVDVTARDAHGNTALAYARQASSQECIDVLLQYGCPDERFVLMATPNLS
RRNNNRNNSSGRVPTII
Function GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system.
Tissue Specificity Widely expressed.
KEGG Pathway
Endocytosis (hsa04144 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Intellectual disability DISMBNXP Definitive Genetic Variation [1]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [2]
Craniofacial microsomia DISYHJ2P Strong Genetic Variation [3]
High blood pressure DISY2OHH Strong Genetic Variation [2]
Knee osteoarthritis DISLSNBJ Strong Genetic Variation [4]
Parkinson disease DISQVHKL Strong Genetic Variation [5]
Schizophrenia DISSRV2N moderate Genetic Variation [6]
Autism DISV4V1Z Limited Genetic Variation [1]
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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
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 GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [7]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [12]
Fulvestrant DM0YZC6 Approved Fulvestrant affects the methylation of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [14]
Camptothecin DM6CHNJ Phase 3 Camptothecin increases the methylation of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [16]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [14]
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11 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 GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [8]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [10]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [13]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [11]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [17]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [18]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [19]
Maleic Acid DM4L0R7 Investigative Maleic Acid increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (AGAP1). [20]
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⏷ Show the Full List of 11 Drug(s)

References

1 A de novo 2q37.2 deletion encompassing AGAP1 and SH3BP4 in a patient with autism and intellectual disability.Eur J Med Genet. 2019 Dec;62(12):103586. doi: 10.1016/j.ejmg.2018.11.020. Epub 2018 Nov 22.
2 Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.PLoS One. 2015 Oct 30;10(10):e0140496. doi: 10.1371/journal.pone.0140496. eCollection 2015.
3 Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia.Nat Commun. 2016 Feb 8;7:10605. doi: 10.1038/ncomms10605.
4 Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.Nat Genet. 2018 Apr;50(4):549-558. doi: 10.1038/s41588-018-0079-y. Epub 2018 Mar 20.
5 A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nat Genet. 2017 Oct;49(10):1511-1516. doi: 10.1038/ng.3955. Epub 2017 Sep 11.
6 Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.Mol Psychiatry. 2012 Sep;17(9):880-6. doi: 10.1038/mp.2012.73. Epub 2012 Jun 12.
7 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.
8 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.
9 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.
10 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
11 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
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 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 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.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 Reduced camptothecin sensitivity of estrogen receptor-positive human breast cancer cells following exposure to di(2-ethylhexyl)phthalate (DEHP) is associated with DNA methylation changes. Environ Toxicol. 2019 Apr;34(4):401-414.
17 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.
18 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.
19 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
20 Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.