Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQSAV5C)

DOT Name Magnesium transporter protein 1 (MAGT1)
Synonyms MagT1; Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit MAGT1; Oligosaccharyl transferase subunit MAGT1; Implantation-associated protein; IAP
Gene Name MAGT1
Related Disease
Acute myelogenous leukaemia ( )
Crohn disease ( )
Inflammatory bowel disease ( )
Intellectual disability ( )
Pancreatic cancer ( )
Tuberculosis ( )
Type-1/2 diabetes ( )
Ulcerative colitis ( )
Acute lymphocytic leukaemia ( )
Adult lymphoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Clear cell renal carcinoma ( )
Colon carcinoma ( )
Congenital disorder of glycosylation ( )
Endometriosis ( )
Epstein barr virus infection ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
leukaemia ( )
Liver cirrhosis ( )
Lung cancer ( )
Lung carcinoma ( )
Nasopharyngeal carcinoma ( )
Pediatric lymphoma ( )
Renal cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia ( )
Bone osteosarcoma ( )
Leukemia ( )
Lymphoma ( )
Osteosarcoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
X-linked intellectual disability ( )
Chronic obstructive pulmonary disease ( )
Immunodeficiency ( )
Intellectual disability, X-linked 95 ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
Neuroblastoma ( )
Plasma cell myeloma ( )
UniProt ID
MAGT1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
6S7T
Pfam ID
PF04756
Sequence
MAARWRFWCVSVTMVVALLIVCDVPSASAQRKKEMVLSEKVSQLMEWTNKRPVIRMNGDK
FRRLVKAPPRNYSVIVMFTALQLHRQCVVCKQADEEFQILANSWRYSSAFTNRIFFAMVD
FDEGSDVFQMLNMNSAPTFINFPAKGKPKRGDTYELQVRGFSAEQIARWIADRTDVNIRV
IRPPNYAGPLMLGLLLAVIGGLVYLRRSNMEFLFNKTGWAFAALCFVLAMTSGQMWNHIR
GPPYAHKNPHTGHVNYIHGSSQAQFVAETHIVLLFNGGVTLGMVLLCEAATSDMDIGKRK
IMCVAGIGLVVLFFSWMLSIFRSKYHGYPYSFLMS
Function
Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with TUSC3. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Has also oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition; May be involved in Mg(2+) transport in epithelial cells.
Tissue Specificity Ubiquitous. Expressed at very low levels in brain, lung and kidney.
KEGG Pathway
N-Glycan biosynthesis (hsa00510 )
Various types of N-glycan biosynthesis (hsa00513 )
Protein processing in endoplasmic reticulum (hsa04141 )
Reactome Pathway
Miscellaneous transport and binding events (R-HSA-5223345 )
Neutrophil degranulation (R-HSA-6798695 )
Maturation of spike protein (R-HSA-9694548 )
Asparagine N-linked glycosylation (R-HSA-446203 )

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Definitive Biomarker [1]
Crohn disease DIS2C5Q8 Definitive Altered Expression [2]
Inflammatory bowel disease DISGN23E Definitive Genetic Variation [2]
Intellectual disability DISMBNXP Definitive Biomarker [3]
Pancreatic cancer DISJC981 Definitive Biomarker [4]
Tuberculosis DIS2YIMD Definitive Biomarker [5]
Type-1/2 diabetes DISIUHAP Definitive Biomarker [6]
Ulcerative colitis DIS8K27O Definitive Altered Expression [2]
Acute lymphocytic leukaemia DISPX75S Strong Altered Expression [7]
Adult lymphoma DISK8IZR Strong Biomarker [8]
Advanced cancer DISAT1Z9 Strong Biomarker [9]
Alzheimer disease DISF8S70 Strong Genetic Variation [10]
Bladder cancer DISUHNM0 Strong Genetic Variation [11]
Breast cancer DIS7DPX1 Strong Biomarker [12]
Breast carcinoma DIS2UE88 Strong Biomarker [12]
Carcinoma DISH9F1N Strong Altered Expression [13]
Cervical cancer DISFSHPF Strong Biomarker [14]
Cervical carcinoma DIST4S00 Strong Biomarker [14]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [15]
Colon carcinoma DISJYKUO Strong Altered Expression [16]
Congenital disorder of glycosylation DIS400QP Strong Biomarker [17]
Endometriosis DISX1AG8 Strong Altered Expression [18]
Epstein barr virus infection DISOO0WT Strong Genetic Variation [19]
Glioblastoma multiforme DISK8246 Strong Genetic Variation [20]
Glioma DIS5RPEH Strong Biomarker [21]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [22]
leukaemia DISS7D1V Strong Biomarker [23]
Liver cirrhosis DIS4G1GX Strong Biomarker [24]
Lung cancer DISCM4YA Strong Biomarker [25]
Lung carcinoma DISTR26C Strong Biomarker [25]
Nasopharyngeal carcinoma DISAOTQ0 Strong Biomarker [26]
Pediatric lymphoma DIS51BK2 Strong Biomarker [8]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [15]
Urinary bladder cancer DISDV4T7 Strong Genetic Variation [11]
Urinary bladder neoplasm DIS7HACE Strong Genetic Variation [11]
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia DISYHOAH Strong X-linked [27]
Bone osteosarcoma DIST1004 moderate Biomarker [28]
Leukemia DISNAKFL moderate Biomarker [23]
Lymphoma DISN6V4S moderate Biomarker [8]
Osteosarcoma DISLQ7E2 moderate Biomarker [28]
Prostate cancer DISF190Y moderate Biomarker [29]
Prostate carcinoma DISMJPLE moderate Biomarker [29]
X-linked intellectual disability DISYJBY3 Disputed X-linked [30]
Chronic obstructive pulmonary disease DISQCIRF Limited Biomarker [31]
Immunodeficiency DIS093I0 Limited Biomarker [32]
Intellectual disability, X-linked 95 DIS1QZO7 Limited X-linked recessive [33]
Melanoma DIS1RRCY Limited Biomarker [34]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [35]
Neuroblastoma DISVZBI4 Limited Biomarker [36]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [37]
------------------------------------------------------------------------------------
⏷ Show the Full List of 50 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Magnesium transporter protein 1 (MAGT1). [38]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Magnesium transporter protein 1 (MAGT1). [39]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Magnesium transporter protein 1 (MAGT1). [40]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Magnesium transporter protein 1 (MAGT1). [41]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Magnesium transporter protein 1 (MAGT1). [42]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Magnesium transporter protein 1 (MAGT1). [43]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Magnesium transporter protein 1 (MAGT1). [45]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Magnesium transporter protein 1 (MAGT1). [44]
------------------------------------------------------------------------------------

References

1 Therapeutic targeting of necroptosis by Smac mimetic bypasses apoptosis resistance in acute myeloid leukemia cells.Oncogene. 2017 Mar;36(11):1487-1502. doi: 10.1038/onc.2016.310. Epub 2016 Nov 21.
2 Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease.World J Gastroenterol. 2012 Jul 7;18(25):3254-9. doi: 10.3748/wjg.v18.i25.3254.
3 The role of MAGT1 in genetic syndromes.Magnes Res. 2015 Jun;28(2):46-55.
4 Omega-3-polyunsaturated fatty acids suppress pancreatic cancer cell growth in vitro and in vivo via downregulation of Wnt/Beta-catenin signaling.Pancreatology. 2011;11(6):574-84. doi: 10.1159/000334468. Epub 2011 Dec 31.
5 Real time PCR in childhood tuberculosis: a valuable diagnostic tool.Indian J Pediatr. 2015 Feb;82(2):189-91. doi: 10.1007/s12098-014-1506-4. Epub 2014 Jul 17.
6 Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition.Nutr Rev. 2019 Oct 1;77(10):710-724. doi: 10.1093/nutrit/nuz015.
7 Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells.Cancer Lett. 2016 May 28;375(1):127-132. doi: 10.1016/j.canlet.2016.02.040. Epub 2016 Mar 2.
8 Signaling pathways involved in the T-cell-mediated immunity against Epstein-Barr virus: Lessons from genetic diseases.Immunol Rev. 2019 Sep;291(1):174-189. doi: 10.1111/imr.12791.
9 IAP genes partake weighty roles in the astogeny and whole body regeneration in the colonial urochordate Botryllus schlosseri.Dev Biol. 2019 Apr 15;448(2):320-341. doi: 10.1016/j.ydbio.2018.10.015. Epub 2018 Oct 30.
10 Underlying Biological Processes in Mild Cognitive Impairment: Amyloidosis Versus Neurodegeneration.J Alzheimers Dis. 2018;64(s1):S647-S657. doi: 10.3233/JAD-179908.
11 NF-B suppresses apoptosis and promotes bladder cancer cell proliferation by upregulating survivin expression in vitro and in vivo.Sci Rep. 2017 Jan 31;7:40723. doi: 10.1038/srep40723.
12 TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-B pathway.J Cancer. 2018 Apr 5;9(8):1349-1356. doi: 10.7150/jca.22390. eCollection 2018.
13 Glucocorticoid cotreatment induces apoptosis resistance toward cancer therapy in carcinomas.Cancer Res. 2003 Jun 15;63(12):3112-20.
14 AT-406, an IAP inhibitor, activates apoptosis and induces radiosensitization of normoxic and hypoxic cervical cancer cells.J Pharmacol Sci. 2014;126(1):56-65. doi: 10.1254/jphs.14079fp. Epub 2014 Aug 27.
15 Overexpression of integrin-associated protein (CD47) in rat kidney treated with a renal carcinogen, ferric nitrilotriacetate.Jpn J Cancer Res. 1997 Feb;88(2):120-8. doi: 10.1111/j.1349-7006.1997.tb00356.x.
16 The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin.Sci Rep. 2017 Jan 17;7:40538. doi: 10.1038/srep40538.
17 Mutations in MAGT1 lead to a glycosylation disorder with a variable phenotype.Proc Natl Acad Sci U S A. 2019 May 14;116(20):9865-9870. doi: 10.1073/pnas.1817815116. Epub 2019 Apr 29.
18 Inhibitor of apoptosis proteins (IAPs) may be effective therapeutic targets for treating endometriosis.Hum Reprod. 2015 Jan;30(1):149-58. doi: 10.1093/humrep/deu288. Epub 2014 Nov 5.
19 Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.J Biol Chem. 2019 Sep 13;294(37):13638-13656. doi: 10.1074/jbc.RA119.008903. Epub 2019 Jul 23.
20 Sensitization of glioblastoma cells to TRAIL-induced apoptosis by IAP- and Bcl-2 antagonism.Cell Death Dis. 2018 Nov 1;9(11):1112. doi: 10.1038/s41419-018-1160-2.
21 microRNA-199a-5p suppresses glioma progression by inhibiting MAGT1.J Cell Biochem. 2019 Sep;120(9):15248-15254. doi: 10.1002/jcb.28791. Epub 2019 Apr 30.
22 Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells.Oncotarget. 2017 Feb 7;8(6):9466-9475. doi: 10.18632/oncotarget.14326.
23 Inhibitor of Apoptosis (IAP) proteins in hematological malignancies: molecular mechanisms and therapeutic opportunities.Leukemia. 2014 Jul;28(7):1414-22. doi: 10.1038/leu.2014.56. Epub 2014 Feb 3.
24 Impact of large volume paracentesis on respiratory parameters including transpulmonary pressure and on transpulmonary thermodilution derived hemodynamics: A prospective study.PLoS One. 2018 Mar 14;13(3):e0193654. doi: 10.1371/journal.pone.0193654. eCollection 2018.
25 Association of cooking oil fumes exposure with lung cancer: involvement of inhibitor of apoptosis proteins in cell survival and proliferation in vitro.Mutat Res. 2007 Apr 2;628(2):107-16. doi: 10.1016/j.mrgentox.2006.12.005. Epub 2006 Dec 22.
26 Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells.BMC Cancer. 2010 Jun 24;10:327. doi: 10.1186/1471-2407-10-327.
27 Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature. 2011 Jul 27;475(7357):471-6. doi: 10.1038/nature10246.
28 IAP antagonists sensitize murine osteosarcoma cells to killing by TNF.Oncotarget. 2016 Jun 7;7(23):33866-86. doi: 10.18632/oncotarget.8980.
29 Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients.PLoS One. 2017 Oct 5;12(10):e0183122. doi: 10.1371/journal.pone.0183122. eCollection 2017.
30 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.
31 Risk of COPD due to indoor air pollution from biomass cooking fuel: a systematic review and meta-analysis.Int J Environ Health Res. 2020 Feb;30(1):75-88. doi: 10.1080/09603123.2019.1575951. Epub 2019 Feb 13.
32 Cutting Edge: Imbalanced Cation Homeostasis in MAGT1-Deficient B Cells Dysregulates B Cell Development and Signaling in Mice.J Immunol. 2018 Apr 15;200(8):2529-2534. doi: 10.4049/jimmunol.1701467. Epub 2018 Mar 26.
33 Oligosaccharyltransferase-subunit mutations in nonsyndromic mental retardation. Am J Hum Genet. 2008 May;82(5):1150-7. doi: 10.1016/j.ajhg.2008.03.021. Epub 2008 May 1.
34 Characterization of ML-IAP protein stability and physiological role in vivo.Biochem J. 2012 Nov 1;447(3):427-36. doi: 10.1042/BJ20121103.
35 Immunostimulating and cancer-reductive experimental therapy with the oxazaphosphorine cytostatic SUM-IAP.Anticancer Drugs. 2018 Jun;29(5):411-415. doi: 10.1097/CAD.0000000000000608.
36 Differential role of RIP1 in Smac mimetic-mediated chemosensitization of neuroblastoma cells.Oncotarget. 2015 Dec 8;6(39):41522-34. doi: 10.18632/oncotarget.6308.
37 Increased resistance to proteasome inhibitors in multiple myeloma mediated by cIAP2--implications for a combinatorial treatment.Oncotarget. 2015 Aug 21;6(24):20621-35. doi: 10.18632/oncotarget.4139.
38 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
39 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.
40 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.
41 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.
42 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
43 A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
44 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.
45 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.