Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAGUVU5)

• DOT Name: Melanoma-associated antigen B2 (MAGEB2)
• Synonyms: Cancer/testis antigen 3.2; CT3.2; DSS-AHC critical interval MAGE superfamily 6; DAM6; MAGE XP-2 antigen; MAGE-B2 antigen
• Gene Name: MAGEB2
• Related Disease:
  Acute myelogenous leukaemia
  Advanced cancer
  Carcinoma
  Clear cell renal carcinoma
  Head-neck squamous cell carcinoma
  Lung neoplasm
  Malignant peripheral nerve sheath tumor
  Myeloid leukaemia
  Neoplasm
  Neurofibromatosis type 1
  Renal cell carcinoma
  Systemic lupus erythematosus
  Melanoma
• UniProt ID: MAGB2_HUMAN
• Pfam ID: PF01454 ; PF12440
• Sequence:
  MPRGQKSKLRAREKRRKARDETRGLNVPQVTEAEEEEAPCCSSSVSGGAASSSPAAGIPQ
  EPQRAPTTAAAAAAGVSSTKSKKGAKSHQGEKNASSSQASTSTKSPSEDPLTRKSGSLVQ
  FLLYKYKIKKSVTKGEMLKIVGKRFREHFPEILKKASEGLSVVFGLELNKVNPNGHTYTF
  IDKVDLTDEESLLSSWDFPRRKLLMPLLGVIFLNGNSATEEEIWEFLNMLGVYDGEEHSV
  FGEPWKLITKDLVQEKYLEYKQVPSSDPPRFQFLWGPRAYAETSKMKVLEFLAKVNGTTP
  CAFPTHYEEALKDEEKAGV
• 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 in testis and placenta, and in a significant fraction of tumors of various histologic types.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[4]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[5]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[6]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Altered Expression	[2]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Neurofibromatosis type 1	DIS53JH9	Strong	Altered Expression	[2]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[3]
Melanoma	DIS1RRCY	moderate	Biomarker	[8]

6 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 Melanoma-associated antigen B2 (MAGEB2).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Melanoma-associated antigen B2 (MAGEB2).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Melanoma-associated antigen B2 (MAGEB2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Melanoma-associated antigen B2 (MAGEB2).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Melanoma-associated antigen B2 (MAGEB2).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Melanoma-associated antigen B2 (MAGEB2).	[15]

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 increases the methylation of Melanoma-associated antigen B2 (MAGEB2).	[14]

References

• [1] The DNA demethylating agent 5-aza-2'-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk Res. 2010 Jul;34(7):899-905. doi: 10.1016/j.leukres.2010.02.004. Epub 2010 Apr 10.
• [2] Aberrant demethylation and expression of MAGEB2 in a subset of malignant peripheral nerve sheath tumors from neurofibromatosis type 1.J Dermatol Sci. 2016 Feb;81(2):118-23. doi: 10.1016/j.jdermsci.2015.11.004. Epub 2015 Nov 28.
• [3] MAGE Xp-2: a member of the MAGE gene family isolated from an expression library using systemic lupus erythematosus sera.Mol Genet Metab. 1998 Jan;63(1):3-13. doi: 10.1006/mgme.1997.2639.
• [4] MAGED4-expression in renal cell carcinoma and identification of an HLA-A*25-restricted MHC class I ligand from solid tumor tissue.Cancer Biol Ther. 2005 Sep;4(9):943-8. doi: 10.4161/cbt.4.9.1907. Epub 2005 Sep 8.
• [5] MAGEB2 is activated by promoter demethylation in head and neck squamous cell carcinoma.PLoS One. 2012;7(9):e45534. doi: 10.1371/journal.pone.0045534. Epub 2012 Sep 24.
• [6] A family of rapidly evolving genes from the sex reversal critical region in Xp21.Mamm Genome. 1995 Sep;6(9):571-80. doi: 10.1007/BF00352360.
• [7] A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence.Mol Cancer Ther. 2015 Mar;14(3):828-34. doi: 10.1158/1535-7163.MCT-14-0796. Epub 2015 Jan 6.
• [8] AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma.Oncotarget. 2016 Sep 20;7(38):60872-60884. doi: 10.18632/oncotarget.11506.
• [9] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [10] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [11] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [12] Treatment of chronic lymphocytic leukemia with a hypomethylating agent induces expression of NXF2, an immunogenic cancer testis antigen. Clin Cancer Res. 2009 May 15;15(10):3406-15. doi: 10.1158/1078-0432.CCR-08-2099. Epub 2009 Apr 28.
• [13] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [14] 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.
• [15] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.