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

DOT Name Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2)
Synonyms Atrophin-1-interacting protein 1; AIP-1; Atrophin-1-interacting protein A; Membrane-associated guanylate kinase inverted 2; MAGI-2
Gene Name MAGI2
Related Disease
Adenocarcinoma ( )
Advanced cancer ( )
Amyloidosis ( )
Anxiety disorder ( )
Benign prostatic hyperplasia ( )
Bipolar disorder ( )
Cardiovascular disease ( )
Cholangiocarcinoma ( )
Chronic kidney disease ( )
Coeliac disease ( )
Colorectal carcinoma ( )
Crohn disease ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Irritable bowel syndrome ( )
Lung cancer ( )
Lung carcinoma ( )
Nephropathy ( )
Nephrotic syndrome 15 ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Steroid-resistant nephrotic syndrome ( )
Systemic sclerosis ( )
Atherosclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Chronic obstructive pulmonary disease ( )
Melanoma ( )
Moyamoya disease ( )
West syndrome ( )
Arteriosclerosis ( )
Graves disease ( )
Hashimoto thyroiditis ( )
Nephrotic syndrome ( )
Ulcerative colitis ( )
Epilepsy ( )
UniProt ID
MAGI2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1UEP; 1UEQ; 1UEW; 1UJV; 1WFV
Pfam ID
PF00625 ; PF16663 ; PF00595 ; PF00397
Sequence
MSKSLKKKSHWTSKVHESVIGRNPEGQLGFELKGGAENGQFPYLGEVKPGKVAYESGSKL
VSEELLLEVNETPVAGLTIRDVLAVIKHCKDPLRLKCVKQGGIVDKDLRHYLNLRFQKGS
VDHELQQIIRDNLYLRTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYED
NYYGTPKPPAEPAPLLLNVTDQILPGATPSAEGKRKRNKSVSNMEKASIEPPEEEEEERP
VVNGNGVVVTPESSEHEDKSAGASGEMPSQPYPAPVYSQPEELKEQMDDTKPTKPEDNEE
PDPLPDNWEMAYTEKGEVYFIDHNTKTTSWLDPRLAKKAKPPEECKENELPYGWEKIDDP
IYGTYYVDHINRRTQFENPVLEAKRKLQQHNMPHTELGTKPLQAPGFREKPLFTRDASQL
KGTFLSTTLKKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVC
VLGHTHADVVKLFQSVPIGQSVNLVLCRGYPLPFDPEDPANSMVPPLAIMERPPPVMVNG
RHNYETYLEYISRTSQSVPDITDRPPHSLHSMPTDGQLDGTYPPPVHDDNVSMASSGATQ
AELMTLTIVKGAQGFGFTIADSPTGQRVKQILDIQGCPGLCEGDLIVEINQQNVQNLSHT
EVVDILKDCPIGSETSLIIHRGGFFSPWKTPKPIMDRWENQGSPQTSLSAPAIPQNLPFP
PALHRSSFPDSTEAFDPRKPDPYELYEKSRAIYESRQQVPPRTSFRMDSSGPDYKELDVH
LRRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRY
VIDLMHHAARNGQVNLTVRRKVLCGGEPCPENGRSPGSVSTHHSSPRSDYATYTNSNHAA
PSSNASPPEGFASHSLQTSDVVIHRKENEGFGFVIISSLNRPESGSTITVPHKIGRIIDG
SPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIPQEELNSPTSAPS
SEKQSPMAQQSPLAQQSPLAQPSPATPNSPIAQPAPPQPLQLQGHENSYRSEVKARQDVK
PDIRQPPFTDYRQPPLDYRQPPGGDYQQPPPLDYRQPPLLDYRQHSPDTRQYPLSDYRQP
QDFDYFTVDMEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGE
STRDMTHARAIELIKSGGRRVRLLLKRGTGQVPEYDEPAPWSSPAAAAPGLPEVGVSLDD
GLAPFSPSHPAPPSDPSHQISPGPTWDIKREHDVRKPKELSACGQKKQRLGEQRERSASP
QRAARPRLEEAPGGQGRPEAGRPASEARAPGLAAADAADAARAGGKEAPRAAAGSELCRR
EGPGAAPAFAGPGGGGSGALEAEGRAGARAGPRPGPRPPGGAPARKAAVAPGPWKVPGSD
KLPSVLKPGASAASR
Function
Seems to act as a scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation. Plays a role in receptor-mediated clathrin-dependent endocytosis which is required for ciliogenesis.
Tissue Specificity Specifically expressed in brain.
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )
PI3K-Akt sig.ling pathway (hsa04151 )
Reactome Pathway
Nephrin family interactions (R-HSA-373753 )

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Amyloidosis DISHTAI2 Strong Genetic Variation [2]
Anxiety disorder DISBI2BT Strong Biomarker [3]
Benign prostatic hyperplasia DISI3CW2 Strong Biomarker [4]
Bipolar disorder DISAM7J2 Strong Biomarker [5]
Cardiovascular disease DIS2IQDX Strong Biomarker [6]
Cholangiocarcinoma DIS71F6X Strong Biomarker [7]
Chronic kidney disease DISW82R7 Strong Biomarker [8]
Coeliac disease DISIY60C Strong Biomarker [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Crohn disease DIS2C5Q8 Strong Genetic Variation [11]
Endometrial cancer DISW0LMR Strong Biomarker [12]
Endometrial carcinoma DISXR5CY Strong Biomarker [12]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [12]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [13]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [14]
Irritable bowel syndrome DIS27206 Strong Biomarker [9]
Lung cancer DISCM4YA Strong Genetic Variation [15]
Lung carcinoma DISTR26C Strong Genetic Variation [15]
Nephropathy DISXWP4P Strong Altered Expression [8]
Nephrotic syndrome 15 DISS43Y1 Strong Autosomal recessive [16]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [17]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [18]
Ovarian cancer DISZJHAP Strong Biomarker [12]
Ovarian neoplasm DISEAFTY Strong Biomarker [12]
Prostate cancer DISF190Y Strong Altered Expression [1]
Prostate carcinoma DISMJPLE Strong Altered Expression [1]
Prostate neoplasm DISHDKGQ Strong Biomarker [1]
Steroid-resistant nephrotic syndrome DISVEBC9 Strong Genetic Variation [19]
Systemic sclerosis DISF44L6 Strong Biomarker [20]
Atherosclerosis DISMN9J3 moderate Altered Expression [21]
Breast cancer DIS7DPX1 moderate Genetic Variation [22]
Breast carcinoma DIS2UE88 moderate Genetic Variation [22]
Chronic obstructive pulmonary disease DISQCIRF moderate Altered Expression [23]
Melanoma DIS1RRCY moderate Genetic Variation [22]
Moyamoya disease DISO62CA moderate Genetic Variation [24]
West syndrome DISLIAU9 moderate Biomarker [25]
Arteriosclerosis DISK5QGC Limited Biomarker [26]
Graves disease DISU4KOQ Limited Genetic Variation [27]
Hashimoto thyroiditis DIS77CDF Limited Genetic Variation [27]
Nephrotic syndrome DISSPSC2 Limited Biomarker [28]
Ulcerative colitis DIS8K27O Limited Genetic Variation [11]
Epilepsy DISBB28L Refuted Autosomal dominant [29]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
NAPQI DM8F5LR Investigative Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) affects the response to substance of NAPQI. [43]
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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 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [30]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [34]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the methylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [38]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [39]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [40]
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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 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [31]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [32]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [33]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [35]
Selenium DM25CGV Approved Selenium decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [36]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [37]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [37]
Belinostat DM6OC53 Phase 2 Belinostat increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [37]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [41]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2). [42]
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⏷ Show the Full List of 10 Drug(s)

References

1 MAGI2 is an independent predictor of biochemical recurrence in prostate cancer.Prostate. 2018 Jun;78(8):616-622. doi: 10.1002/pros.23506. Epub 2018 Mar 14.
2 Antiamyloidogenic Activity of A42-Binding Peptoid in Modulating Amyloid Oligomerization.Small. 2017 Jan;13(1). doi: 10.1002/smll.201602857. Epub 2016 Oct 7.
3 S-SCAM, a rare copy number variation gene, induces schizophrenia-related endophenotypes in transgenic mouse model.J Neurosci. 2015 Feb 4;35(5):1892-904. doi: 10.1523/JNEUROSCI.3658-14.2015.
4 MAGI-2 in prostate cancer: an immunohistochemical study.Hum Pathol. 2016 Jun;52:83-91. doi: 10.1016/j.humpath.2016.01.003. Epub 2016 Feb 4.
5 MAGI1 copy number variation in bipolar affective disorder and schizophrenia.Biol Psychiatry. 2012 May 15;71(10):922-30. doi: 10.1016/j.biopsych.2012.01.020. Epub 2012 Feb 28.
6 AIP1-mediated stress signaling in atherosclerosis and arteriosclerosis.Curr Atheroscler Rep. 2015 May;17(5):503. doi: 10.1007/s11883-015-0503-z.
7 Outcome and Genetic Factors in IgG4-Associated Autoimmune Pancreatitis and Cholangitis: A Single Center Experience.Gastroenterol Res Pract. 2017;2017:6126707. doi: 10.1155/2017/6126707. Epub 2017 Mar 2.
8 Weighted Gene Correlation Network Analysis (WGCNA) Detected Loss of MAGI2 Promotes Chronic Kidney Disease (CKD) by Podocyte Damage.Cell Physiol Biochem. 2018;51(1):244-261. doi: 10.1159/000495205. Epub 2018 Nov 16.
9 Intestinal epithelial barrier dysfunction in disease and possible therapeutical interventions.Curr Med Chem. 2011;18(3):398-426. doi: 10.2174/092986711794839179.
10 Suppression of inflammation and tissue damage by a hookworm recombinant protein in experimental colitis.Clin Transl Immunology. 2017 Oct 6;6(10):e157. doi: 10.1038/cti.2017.42. eCollection 2017 Oct.
11 Replication of genetic variation in the MYO9B gene in Crohn's disease.Hum Immunol. 2011 Jul;72(7):592-7. doi: 10.1016/j.humimm.2011.03.025. Epub 2011 Apr 12.
12 The feasibility of detecting endometrial and ovarian cancer using DNA methylation biomarkers in cervical scrapings.J Gynecol Oncol. 2018 Jan;29(1):e17. doi: 10.3802/jgo.2018.29.e17.
13 Low expression level of ASK1-interacting protein-1 correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer.Onco Targets Ther. 2018 Nov 1;11:7699-7707. doi: 10.2147/OTT.S178131. eCollection 2018.
14 MAGI2 enhances the sensitivity of BEL-7404 human hepatocellular carcinoma cells to staurosporine-induced apoptosis by increasing PTEN stability.Int J Mol Med. 2013 Aug;32(2):439-47. doi: 10.3892/ijmm.2013.1411. Epub 2013 Jun 7.
15 A common genetic variant (97906C>A) of DAB2IP/AIP1 is associated with an increased risk and early onset of lung cancer in Chinese males.PLoS One. 2011;6(10):e26944. doi: 10.1371/journal.pone.0026944. Epub 2011 Oct 26.
16 MAGI-2 is critical for the formation and maintenance of the glomerular filtration barrier in mouse kidney. Am J Pathol. 2014 Oct;184(10):2699-708. doi: 10.1016/j.ajpath.2014.06.019. Epub 2014 Aug 7.
17 Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes.BMC Genet. 2017 Dec 8;18(1):105. doi: 10.1186/s12863-017-0572-9.
18 LncRNAs and EGFRvIII sequestered in TEPs enable blood-based NSCLC diagnosis.Cancer Manag Res. 2018 Jun 8;10:1449-1459. doi: 10.2147/CMAR.S164227. eCollection 2018.
19 Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout.Kidney Int. 2019 May;95(5):1079-1090. doi: 10.1016/j.kint.2018.12.026. Epub 2019 Mar 5.
20 Corticosteroid-sparing benefit of intravenous immunoglobulin in systemic sclerosis-associated myopathy: A comparative study in 52 patients.Autoimmun Rev. 2020 Jan;19(1):102431. doi: 10.1016/j.autrev.2019.102431. Epub 2019 Nov 14.
21 Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2.Front Physiol. 2018 Apr 20;9:396. doi: 10.3389/fphys.2018.00396. eCollection 2018.
22 AIP1 Expression in Tumor Niche Suppresses Tumor Progression and Metastasis.Cancer Res. 2015 Sep 1;75(17):3492-504. doi: 10.1158/0008-5472.CAN-15-0088. Epub 2015 Jul 2.
23 Novel genes for airway wall thickness identified with combined genome-wide association and expression analyses.Am J Respir Crit Care Med. 2015 Mar 1;191(5):547-56. doi: 10.1164/rccm.201405-0840OC.
24 Novel Susceptibility Loci for Moyamoya Disease Revealed by a Genome-Wide Association Study.Stroke. 2018 Jan;49(1):11-18. doi: 10.1161/STROKEAHA.117.017430.
25 MAGI2 Mutations Cause Congenital Nephrotic Syndrome.J Am Soc Nephrol. 2017 May;28(5):1614-1621. doi: 10.1681/ASN.2016040387. Epub 2016 Dec 8.
26 Short AIP1 (ASK1-Interacting Protein-1) Isoform Localizes to the Mitochondria and Promotes Vascular Dysfunction.Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):112-127. doi: 10.1161/ATVBAHA.119.312976. Epub 2019 Oct 17.
27 The MAGI2 gene polymorphism rs2160322 is associated with Graves' disease but not with Hashimoto's thyroiditis.J Endocrinol Invest. 2019 Jul;42(7):843-850. doi: 10.1007/s40618-018-0990-1. Epub 2018 Dec 8.
28 An unexpected role of steroid on podocytes: from zebrafish to human nephrotic syndrome?.Kidney Int. 2019 May;95(5):1015-1017. doi: 10.1016/j.kint.2019.01.044.
29 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
30 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.
31 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
32 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.
33 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.
34 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.
35 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.
36 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
37 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.
38 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.
39 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.
40 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.
41 Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
42 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.
43 Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.