Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN5FCSD)

• DOT Name: Melanoma-associated antigen C2 (MAGEC2)
• Synonyms: Cancer/testis antigen 10; CT10; Hepatocellular carcinoma-associated antigen 587; MAGE-C2 antigen; MAGE-E1 antigen
• Gene Name: MAGEC2
• UniProt ID: MAGC2_HUMAN
• Pfam ID: PF01454
• Sequence:
  MPPVPGVPFRNVDNDSPTSVELEDWVDAQHPTDEEEEEASSASSTLYLVFSPSSFSTSSS
  LILGGPEEEEVPSGVIPNLTESIPSSPPQGPPQGPSQSPLSSCCSSFSWSSFSEESSSQK
  GEDTGTCQGLPDSESSFTYTLDEKVAELVEFLLLKYEAEEPVTEAEMLMIVIKYKDYFPV
  ILKRAREFMELLFGLALIEVGPDHFCVFANTVGLTDEGSDDEGMPENSLLIIILSVIFIK
  GNCASEEVIWEVLNAVGVYAGREHFVYGEPRELLTKVWVQGHYLEYREVPHSSPPYYEFL
  WGPRAHSESIKKKVLEFLAKLNNTVPSSFPSWYKDALKDVEERVQATIDTADDATVMASE
  SLSVMSSNVSFSE
• Function: 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 in presence of Ubl-conjugating enzyme UBE2H leading to p53/TP53 degradation. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzymes (E2) at the E3:substrate complex.
• Tissue Specificity: Not expressed in normal tissues, except in germ cells in the seminiferous tubules and in Purkinje cells of the cerebellum. Expressed in various tumors, including melanoma, lymphoma, as well as pancreatic cancer, mammary gland cancer, non-small cell lung cancer and liver cancer. In hepatocellular carcinoma, there is an inverse correlation between tumor differentiation and protein expression, i.e. the lower the differentiation, the higher percentage of expression.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Melanoma-associated antigen C2 (MAGEC2).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Melanoma-associated antigen C2 (MAGEC2).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Melanoma-associated antigen C2 (MAGEC2).	[3]

References

• [1] 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.
• [2] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [3] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.