Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW3Y5M4)

• DOT Name: Melanoma-associated antigen 3 (MAGEA3)
• Synonyms: Antigen MZ2-D; Cancer/testis antigen 1.3; CT1.3; MAGE-3 antigen
• Gene Name: MAGEA3
• UniProt ID: MAGA3_HUMAN
• PDB ID: 1QEW; 4V0P; 5BRZ
• Pfam ID: PF01454 ; PF12440
• Sequence:
  MPLEQRSQHCKPEEGLEARGEALGLVGAQAPATEEQEAASSSSTLVEVTLGEVPAAESPD
  PPQSPQGASSLPTTMNYPLWSQSYEDSSNQEEEGPSTFPDLESEFQAALSRKVAELVHFL
  LLKYRAREPVTKAEMLGSVVGNWQYFFPVIFSKASSSLQLVFGIELMEVDPIGHLYIFAT
  CLGLSYDGLLGDNQIMPKAGLLIIVLAIIAREGDCAPEEKIWEELSVLEVFEGREDSILG
  DPKKLLTQHFVQENYLEYRQVPGSDPACYEFLWGPRALVETSYVKVLHHMVKISGGPHIS
  YPPLHEWVLREGEE
• Function: Activator of ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases that acts as a repressor of autophagy. May enhance ubiquitin ligase activity of TRIM28 and stimulate p53/TP53 ubiquitination by TRIM28. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. May play a role in embryonal development and tumor transformation or aspects of tumor progression. In vitro promotes cell viability in melanoma cell lines. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes.
• Tissue Specificity: Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes and placenta. Never expressed in kidney tumors, Leukemias and lymphomas.

Molecular Interaction Atlas (MIA) of This DOT

3 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 3 (MAGEA3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Melanoma-associated antigen 3 (MAGEA3).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Melanoma-associated antigen 3 (MAGEA3).	[6]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Melanoma-associated antigen 3 (MAGEA3).	[2]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Melanoma-associated antigen 3 (MAGEA3).	[3]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Melanoma-associated antigen 3 (MAGEA3).	[4]

References

• [1] 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.
• [2] 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.
• [3] Epigenetic modulation of MAGE-A3 antigen expression in multiple myeloma following treatment with the demethylation agent 5-azacitidine and the histone deacetlyase inhibitor MGCD0103. Cytotherapy. 2011 May;13(5):618-28. doi: 10.3109/14653249.2010.529893. Epub 2010 Dec 20.
• [4] 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.
• [5] 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.
• [6] 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.