Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1XKBZ0)

DOT Name AT-rich interactive domain-containing protein 4A (ARID4A)
Synonyms ARID domain-containing protein 4A; Retinoblastoma-binding protein 1; RBBP-1
Gene Name ARID4A
Related Disease
Acute myelogenous leukaemia ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colorectal carcinoma ( )
leukaemia ( )
Leukemia ( )
Neoplasm ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Coronary heart disease ( )
Prostate cancer ( )
UniProt ID
ARI4A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2LCC; 2MAM; 2YRV; 6BPH; 6L87; 7SMC; 7V8N
Pfam ID
PF01388 ; PF08169 ; PF11717
Sequence
MKAADEPAYLTVGTDVSAKYRGAFCEAKIKTVKRLVKVKVLLKQDNTTQLVQDDQVKGPL
RVGAIVETRTSDGSFQEAIISKLTDASWYTVVFDDGDERTLRRTSLCLKGERHFAESETL
DQLPLTNPEHFGTPVIAKKTNRGRRSSLPVTEDEKEEESSEEEDEDKRRLNDELLGKVVS
VVSATERTEWYPALVISPSCNDDITVKKDQCLVRSFIDSKFYSIARKDIKEVDILNLPES
ELSTKPGLQKASIFLKTRVVPDNWKMDISEILESSSSDDEDGPAEENDEEKEKEAKKTEE
EVPEEELDPEERDNFLQQLYKFMEDRGTPINKPPVLGYKDLNLFKLFRLVYHQGGCDNID
SGAVWKQIYMDLGIPILNSAASYNVKTAYRKYLYGFEEYCRSANIQFRTVHHHEPKVKEE
KKDLEESMEEALKLDQEMPLTEVKSEPEENIDSNSESEREEIELKSPRGRRRIARDVNSI
KKEIEEEKTEDKLKDNDTENKDVDDDYETAEKKENELLLGRKNTPKQKEKKIKKQEDSDK
DSDEEEEKSQEREETESKCDSEGEEDEEDMEPCLTGTKVKVKYGRGKTQKIYEASIKSTE
IDDGEVLYLVHYYGWNVRYDEWVKADRIIWPLDKGGPKKKQKKKAKNKEDSEKDEKRDEE
RQKSKRGRPPLKSTLSSNMPYGLSKTANSEGKSDSCSSDSETEDALEKNLINEELSLKDE
LEKNENLNDDKLDEENPKISAHILKENDRTQMQPLETLKLEVGENEQIVQIFGNKMEKTE
EVKKEAEKSPKGKGRRSKTKDLSLEIIKISSFGQNEAGSEPHIEAHSLELSSLDNKNFSS
ATEDEIDQCVKEKKLKRKILGQSSPEKKIRIENGMEMTNTVSQERTSDCIGSEGMKNLNF
EQHFERENEGMPSLIAESNQCIQQLTSERFDSPAEETVNIPLKEDEDAMPLIGPETLVCH
EVDLDDLDEKDKTSIEDVAVESSESNSLVSIPPALPPVVQHNFSVASPLTLSQDESRSVK
SESDITIEVDSIAEESQEGLCERESANGFETNVASGTCSIIVQERESREKGQKRPSDGNS
GLMAKKQKRTPKRTSAAAKNEKNGTGQSSDSEDLPVLDNSSKCTPVKHLNVSKPQKLARS
PARISPHIKDGEKDKHREKHPNSSPRTYKWSFQLNELDNMNSTERISFLQEKLQEIRKYY
MSLKSEVATIDRRRKRLKKKDREVSHAGASMSSASSDTGMSPSSSSPPQNVLAVECR
Function
DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor). May function as part of an mSin3A repressor complex. Has no intrinsic transcriptional activity. Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B. Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier. Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor.
Reactome Pathway
Potential therapeutics for SARS (R-HSA-9679191 )
HDACs deacetylate histones (R-HSA-3214815 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [1]
Breast cancer DIS7DPX1 Strong Genetic Variation [2]
Breast carcinoma DIS2UE88 Strong Genetic Variation [2]
Breast neoplasm DISNGJLM Strong Altered Expression [2]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [3]
leukaemia DISS7D1V Strong Biomarker [4]
Leukemia DISNAKFL Strong Biomarker [4]
Neoplasm DISZKGEW Strong Biomarker [3]
Prostate carcinoma DISMJPLE Strong Altered Expression [5]
Prostate neoplasm DISHDKGQ Strong Biomarker [6]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [7]
Prostate cancer DISF190Y Limited Biomarker [6]
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⏷ Show the Full List of 12 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 decreases the methylation of AT-rich interactive domain-containing protein 4A (ARID4A). [8]
Quercetin DM3NC4M Approved Quercetin increases the phosphorylation of AT-rich interactive domain-containing protein 4A (ARID4A). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of AT-rich interactive domain-containing protein 4A (ARID4A). [18]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of AT-rich interactive domain-containing protein 4A (ARID4A). [19]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of AT-rich interactive domain-containing protein 4A (ARID4A). [12]
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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 decreases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [10]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [11]
Testosterone DM7HUNW Approved Testosterone increases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [13]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [14]
Menthol DMG2KW7 Approved Menthol increases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [15]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [16]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [17]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [20]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [21]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of AT-rich interactive domain-containing protein 4A (ARID4A). [22]
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⏷ Show the Full List of 11 Drug(s)

References

1 Identification of chromatin remodeling genes Arid4a and Arid4b as leukemia suppressor genes.J Natl Cancer Inst. 2008 Sep 3;100(17):1247-59. doi: 10.1093/jnci/djn253. Epub 2008 Aug 26.
2 Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells.J Biol Chem. 2008 Mar 21;283(12):7438-44. doi: 10.1074/jbc.M709446200. Epub 2008 Jan 22.
3 Exome sequencing reveals frequent inactivating mutations in ARID1A, ARID1B, ARID2 and ARID4A in microsatellite unstable colorectal cancer.Int J Cancer. 2014 Aug 1;135(3):611-23. doi: 10.1002/ijc.28705. Epub 2014 Jan 13.
4 Structural insight into recognition of methylated histone tails by retinoblastoma-binding protein 1.J Biol Chem. 2012 Mar 9;287(11):8531-40. doi: 10.1074/jbc.M111.299149. Epub 2012 Jan 12.
5 Downregulation of ARID4A and ARID4B promote tumor progression and directly regulated by microRNA-30d in patient with prostate cancer.J Cell Biochem. 2018 Sep;119(9):7245-7255. doi: 10.1002/jcb.26913. Epub 2018 May 24.
6 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
7 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.
8 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.
9 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
10 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
11 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.
12 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.
13 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.
14 In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
15 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
16 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.
17 Differential expression of genes induced by resveratrol in LNCaP cells: P53-mediated molecular targets. Int J Cancer. 2003 Mar 20;104(2):204-12.
18 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.
19 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
20 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.
21 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
22 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.