Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO37U7W)

DOT Name Melanoma-associated antigen D4 (MAGED4B)
Synonyms MAGE-D4 antigen; MAGE-E1 antigen
Gene Name MAGED4B
Related Disease
Head and neck cancer ( )
Lung carcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Carcinoma of esophagus ( )
Cholangiocarcinoma ( )
Epithelial ovarian cancer ( )
Esophageal cancer ( )
Esophageal squamous cell carcinoma ( )
Germ cell tumor ( )
Glioblastoma multiforme ( )
Glioma ( )
Head and neck carcinoma ( )
Hepatocellular carcinoma ( )
leukaemia ( )
Leukemia ( )
Lung neoplasm ( )
Metastatic malignant neoplasm ( )
Neoplasm of esophagus ( )
Nongerminomatous germ cell tumor ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Plasma cell myeloma ( )
Small lymphocytic lymphoma ( )
Small-cell lung cancer ( )
Stomach cancer ( )
Testicular cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Cutaneous melanoma ( )
Liver cancer ( )
Lung cancer ( )
Adenocarcinoma ( )
Head-neck squamous cell carcinoma ( )
Melanocytic nevus ( )
Neuroblastoma ( )
Non-small-cell lung cancer ( )
Rectal carcinoma ( )
Serous cystadenocarcinoma ( )
UniProt ID
MAGD4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF01454
Sequence
MAEGSFSVQSESYSVEDMDEGSDEVGEEEMVEGNDYEEFGAFGGYGTLTSFDIHILRAFG
SLGPGLRILSNEPWELENPVLAQTLVEALQLDPETLANETAARAANVARAAASNRAARAA
AAAARTAFSQVVASHRVATPQVSGEDTQPTTYAAEAQGPTPEPPLASPQTSQMLVTSKMA
APEAPATSAQSQTGSPAQEAATEGPSSACAFSQAPCAREVDANRPSTAFLGQNDVFDFTQ
PAGVSGMAFPRPKRPAPAQEAATEGPSAASGVPQTGPGREVAATRPKTTKSGKALAKTRW
VEPQNVVAAAAAKAKMATSIPEPEGAAAATAQHSAEPWARMGGKRTKKSKHLDDEYESSE
EERETPAVPPTWRASQPSLTVRAQLAPRPPMAPRSQIPSRHVLCLPPRNVTLLQERANKL
VKYLMIKDYKKIPIKRADMLKDVIREYDEHFPEIIERATYTLEKKFGIHLKEIDKEEHLY
ILVCTRDSSARLLGKTKDTPRLSLLLVILGVIFMNGNRASEAVLWEALRKMGLRPGVRHP
FLGDLRKLITDDFVKQKYLEYKKIPNSNPPEYEFLWGLRARHETSKMRVLRFIAQNQNRD
PREWKAHFLEAVDDAFKTMDVDMAEEHARAQMRAQMNIGDEALIGRWSWDDIQVELLTWD
EDGDFGDAWARIPFAFWARYHQYILNSNRANRRATWRAGVSSGTNGGASTSVLDGPSTSS
TIRTRNAARAGASFFSWIQHR
Function
May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex.
Tissue Specificity Expressed only in brain and ovary among normal tissues. Isoform 1 and isoform 2 are specifically expressed in glioma cells among cancer cells. Detected in some renal cell carcinoma samples.

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Head and neck cancer DISBPSQZ Definitive Biomarker [1]
Lung carcinoma DISTR26C Definitive Biomarker [1]
Adult glioblastoma DISVP4LU Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [3]
Breast cancer DIS7DPX1 Strong Genetic Variation [4]
Breast carcinoma DIS2UE88 Strong Genetic Variation [4]
Carcinoma DISH9F1N Strong Altered Expression [5]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [6]
Cholangiocarcinoma DIS71F6X Strong Biomarker [7]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [8]
Esophageal cancer DISGB2VN Strong Altered Expression [6]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [9]
Germ cell tumor DIS62070 Strong Altered Expression [10]
Glioblastoma multiforme DISK8246 Strong Altered Expression [2]
Glioma DIS5RPEH Strong Biomarker [11]
Head and neck carcinoma DISOU1DS Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [13]
leukaemia DISS7D1V Strong Altered Expression [14]
Leukemia DISNAKFL Strong Altered Expression [14]
Lung neoplasm DISVARNB Strong Altered Expression [15]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [16]
Neoplasm of esophagus DISOLKAQ Strong Altered Expression [6]
Nongerminomatous germ cell tumor DISQOQJU Strong Altered Expression [10]
Ovarian cancer DISZJHAP Strong Altered Expression [8]
Ovarian neoplasm DISEAFTY Strong Altered Expression [8]
Plasma cell myeloma DIS0DFZ0 Strong Altered Expression [17]
Small lymphocytic lymphoma DIS30POX Strong Biomarker [14]
Small-cell lung cancer DISK3LZD Strong Altered Expression [18]
Stomach cancer DISKIJSX Strong Altered Expression [19]
Testicular cancer DIS6HNYO Strong Genetic Variation [20]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W moderate Altered Expression [21]
Cutaneous melanoma DIS3MMH9 moderate Altered Expression [22]
Liver cancer DISDE4BI moderate Altered Expression [21]
Lung cancer DISCM4YA moderate Biomarker [1]
Adenocarcinoma DIS3IHTY Limited Altered Expression [23]
Head-neck squamous cell carcinoma DISF7P24 Limited Altered Expression [24]
Melanocytic nevus DISYS32D Limited Altered Expression [25]
Neuroblastoma DISVZBI4 Limited Biomarker [26]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [23]
Rectal carcinoma DIS8FRR7 Limited Altered Expression [24]
Serous cystadenocarcinoma DISVK716 Limited Altered Expression [8]
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⏷ Show the Full List of 41 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Fluorouracil DMUM7HZ Approved Melanoma-associated antigen D4 (MAGED4B) affects the response to substance of Fluorouracil. [33]
Mitoxantrone DMM39BF Approved Melanoma-associated antigen D4 (MAGED4B) affects the response to substance of Mitoxantrone. [33]
Cyclophosphamide DM4O2Z7 Approved Melanoma-associated antigen D4 (MAGED4B) affects the response to substance of Cyclophosphamide. [33]
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2 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 Melanoma-associated antigen D4 (MAGED4B). [27]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Melanoma-associated antigen D4 (MAGED4B). [31]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Melanoma-associated antigen D4 (MAGED4B). [28]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Melanoma-associated antigen D4 (MAGED4B). [29]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Melanoma-associated antigen D4 (MAGED4B). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Melanoma-associated antigen D4 (MAGED4B). [32]
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References

1 A new strategy for the diagnosis of MAGE-expressing cancers.J Immunol Methods. 2002 Aug 1;266(1-2):79-86. doi: 10.1016/s0022-1759(02)00105-9.
2 HER-2, gp100, and MAGE-1 are expressed in human glioblastoma and recognized by cytotoxic T cells.Cancer Res. 2004 Jul 15;64(14):4980-6. doi: 10.1158/0008-5472.CAN-03-3504.
3 Opa interacting protein 5 (OIP5) is a novel cancer-testis specific gene in gastric cancer.Ann Surg Oncol. 2007 Feb;14(2):885-92. doi: 10.1245/s10434-006-9121-x. Epub 2006 Dec 7.
4 MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation.Cancer Res. 1996 Jan 1;56(1):16-20.
5 Expression of MAGE-1, -2, and -3 genes in gastric carcinomas and cancer cell lines derived from Korean patients.J Korean Med Sci. 2001 Feb;16(1):62-8. doi: 10.3346/jkms.2001.16.1.62.
6 Overexpression of melanoma-associated antigen D4 is an independent prognostic factor in squamous cell carcinoma of the esophagus.Dis Esophagus. 2015 Feb-Mar;28(2):188-95. doi: 10.1111/dote.12156. Epub 2013 Oct 21.
7 Genetic detection for micrometastasis in lymph node of biliary tract carcinoma.Clin Cancer Res. 2000 Jun;6(6):2326-32.
8 Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines. BMC Cancer. 2010 Apr 27;10:163.
9 Expression, Function, and Prognostic Value of MAGE-D4 Protein in Esophageal Squamous Cell Carcinoma.Anticancer Res. 2019 Nov;39(11):6015-6023. doi: 10.21873/anticanres.13807.
10 Expression of MAGE genes in testicular germ cell tumors.Urology. 1999 Apr;53(4):843-7. doi: 10.1016/s0090-4295(98)00618-9.
11 Prognostic and clinicopathological value of melanoma-associated antigen D4 in patients with glioma.Oncol Lett. 2018 Apr;15(4):4151-4160. doi: 10.3892/ol.2018.7884. Epub 2018 Jan 26.
12 Expression of cancer testis antigens in head and neck squamous cell carcinomas.Head Neck. 2006 Jul;28(7):614-9. doi: 10.1002/hed.20380.
13 Evaluation of MAGE-D4 expression in hepatocellular carcinoma in Japanese patients.J Surg Oncol. 2013 Dec;108(8):557-62. doi: 10.1002/jso.23440. Epub 2013 Sep 20.
14 Expression of the MAGE gene family in human lymphocytic leukemia.Cancer Immunol Immunother. 1995 Aug;41(2):90-103. doi: 10.1007/s002620050205.
15 Expression of mage genes by non-small-cell lung carcinomas.Int J Cancer. 1994 Mar 15;56(6):826-9. doi: 10.1002/ijc.2910560612.
16 Comparative analysis of genetically modified dendritic cells and tumor cells as therapeutic cancer vaccines.J Exp Med. 2000 May 15;191(10):1699-708. doi: 10.1084/jem.191.10.1699.
17 The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells.Eur J Immunol. 2000 Mar;30(3):803-9. doi: 10.1002/1521-4141(200003)30:3<803::AID-IMMU803>3.0.CO;2-P.
18 IFN-gamma gene transfer restores HLA-class I expression and MAGE-3 antigen presentation to CTL in HLA-deficient small cell lung cancer.Gene Ther. 1997 Oct;4(10):1029-35. doi: 10.1038/sj.gt.3300489.
19 Melanoma antigen-encoding gene-1 expression in invasive gastric carcinoma: correlation with stage of disease.J Surg Oncol. 1997 Mar;64(3):195-201. doi: 10.1002/(sici)1096-9098(199703)64:3<195::aid-jso4>3.0.co;2-5.
20 Pattern of cancer/testis antigen expression in lung cancer patients.Int J Mol Med. 2012 Apr;29(4):656-62. doi: 10.3892/ijmm.2012.896. Epub 2012 Jan 24.
21 Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide.Chin Med J (Engl). 2002 Jul;115(7):1002-5.
22 Infrequent expression of the MAGE gene family in uveal melanomas.Int J Cancer. 1996 Jun 11;66(6):738-42. doi: 10.1002/(SICI)1097-0215(19960611)66:6<738::AID-IJC5>3.0.CO;2-0.
23 Expression of MAGE-D4, a novel MAGE family antigen, is correlated with tumor-cell proliferation of non-small cell lung cancer.Lung Cancer. 2006 Jan;51(1):79-88. doi: 10.1016/j.lungcan.2005.08.012. Epub 2005 Oct 12.
24 In vitro evaluation of dual-antigenic PV1 peptide vaccine in head and neck cancer patients.Hum Vaccin Immunother. 2019;15(1):167-178. doi: 10.1080/21645515.2018.1520584. Epub 2018 Oct 12.
25 Melanoma antigen-encoding gene expression in melanocytic naevi and cutaneous malignant melanomas.Br J Dermatol. 1999 Jan;140(1):106-8. doi: 10.1046/j.1365-2133.1999.02616.x.
26 Expression and clinical relevance of NY-ESO-1, MAGE-1 and MAGE-3 in neuroblastoma.Anticancer Res. 1999 May-Jun;19(3B):2205-9.
27 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.
28 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.
29 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
30 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
31 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.
32 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
33 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.