Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ0YOTY)

• DOT Name: Melanoma-associated antigen 2 (MAGEA2)
• Synonyms: Cancer/testis antigen 1.2; CT1.2; MAGE-2 antigen
• Gene Name: MAGEA2
• UniProt ID: MAGA2_HUMAN
• Pfam ID: PF01454 ; PF12440
• Sequence:
  MPLEQRSQHCKPEEGLEARGEALGLVGAQAPATEEQQTASSSSTLVEVTLGEVPAADSPS
  PPHSPQGASSFSTTINYTLWRQSDEGSSNQEEEGPRMFPDLESEFQAAISRKMVELVHFL
  LLKYRAREPVTKAEMLESVLRNCQDFFPVIFSKASEYLQLVFGIEVVEVVPISHLYILVT
  CLGLSYDGLLGDNQVMPKTGLLIIVLAIIAIEGDCAPEEKIWEELSMLEVFEGREDSVFA
  HPRKLLMQDLVQENYLEYRQVPGSDPACYEFLWGPRALIETSYVKVLHHTLKIGGEPHIS
  YPPLHERALREGEE
• Function: Reduces p53/TP53 transactivation function through recruitment of HDAC3 to p53/TP53 transcription sites. Also represses p73/TP73 activity. Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. In vitro enhances ubiquitin ligase activity of TRIM28 and stimulates p53/TP53 ubiquitination by TRIM28 potentially in presence of Ubl-conjugating enzyme UBE2H. 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. Negatively regulates acetylation and sumoylation of PML and represses PML-induced p53/TP53 acetylation and activation.
• 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.

Molecular Interaction Atlas (MIA) of This DOT

1 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 2 (MAGEA2).	[1]

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 2 (MAGEA2).	[2]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Melanoma-associated antigen 2 (MAGEA2).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Melanoma-associated antigen 2 (MAGEA2).	[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] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [3] 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.
• [4] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.