Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8S0O2)

• DOT Name: Melanoma-associated antigen 6 (MAGEA6)
• Synonyms: Cancer/testis antigen 1.6; CT1.6; MAGE-6 antigen; MAGE3B antigen
• Gene Name: MAGEA6
• UniProt ID: MAGA6_HUMAN
• Pfam ID: PF01454 ; PF12440
• Sequence:
  MPLEQRSQHCKPEEGLEARGEALGLVGAQAPATEEQEAASSSSTLVEVTLGEVPAAESPD
  PPQSPQGASSLPTTMNYPLWSQSYEDSSNQEEEGPSTFPDLESEFQAALSRKVAKLVHFL
  LLKYRAREPVTKAEMLGSVVGNWQYFFPVIFSKASDSLQLVFGIELMEVDPIGHVYIFAT
  CLGLSYDGLLGDNQIMPKTGFLIIILAIIAKEGDCAPEEKIWEELSVLEVFEGREDSIFG
  DPKKLLTQYFVQENYLEYRQVPGSDPACYEFLWGPRALIETSYVKVLHHMVKISGGPRIS
  YPLLHEWALREGEE
• 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 tumor transformation or aspects of tumor progression. In vitro promotes cell viability in melanoma cell lines.
• 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

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Melanoma-associated antigen 6 (MAGEA6) affects the response to substance of Methotrexate.	[5]
Etoposide	DMNH3PG	Approved	Melanoma-associated antigen 6 (MAGEA6) affects the response to substance of Etoposide.	[5]
Mitomycin	DMH0ZJE	Approved	Melanoma-associated antigen 6 (MAGEA6) affects the response to substance of Mitomycin.	[5]
Mitoxantrone	DMM39BF	Approved	Melanoma-associated antigen 6 (MAGEA6) affects the response to substance of Mitoxantrone.	[5]

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 6 (MAGEA6).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Melanoma-associated antigen 6 (MAGEA6).	[2]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Melanoma-associated antigen 6 (MAGEA6).	[3]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Melanoma-associated antigen 6 (MAGEA6).	[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] The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma. Int J Cancer. 2008 Jun 1;122(11):2542-53. doi: 10.1002/ijc.23407.
• [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] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [5] 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.