Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLT6Q3G)

• DOT Name: Melanoma-associated antigen 11 (MAGEA11)
• Synonyms: Cancer/testis antigen 1.11; CT1.11; MAGE-11 antigen
• Gene Name: MAGEA11
• Related Disease:
  Advanced cancer
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Head-neck squamous cell carcinoma
  Castration-resistant prostate carcinoma
  Epithelial ovarian cancer
• UniProt ID: MAGAB_HUMAN
• PDB ID: 6WJH
• Pfam ID: PF01454 ; PF12440
• Sequence:
  METQFRRGGLGCSPASIKRKKKREDSGDFGLQVSTMFSEDDFQSTERAPYGPQLQWSQDL
  PRVQVFREQANLEDRSPRRTQRITGGEQVLWGPITQIFPTVRPADLTRVIMPLEQRSQHC
  KPEEGLQAQEEDLGLVGAQALQAEEQEAAFFSSTLNVGTLEELPAAESPSPPQSPQEESF
  SPTAMDAIFGSLSDEGSGSQEKEGPSTSPDLIDPESFSQDILHDKIIDLVHLLLRKYRVK
  GLITKAEMLGSVIKNYEDYFPEIFREASVCMQLLFGIDVKEVDPTSHSYVLVTSLNLSYD
  GIQCNEQSMPKSGLLIIVLGVIFMEGNCIPEEVMWEVLSIMGVYAGREHFLFGEPKRLLT
  QNWVQEKYLVYRQVPGTDPACYEFLWGPRAHAETSKMKVLEYIANANGRDPTSYPSLYED
  ALREEGEGV
• Function: Acts as androgen receptor coregulator that increases androgen receptor activity by modulating the receptors interdomain interaction. May play a role in embryonal development and tumor transformation or aspects of tumor progression.
• Tissue Specificity: Expressed in tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma. Expressed in testis, ovary, prostate, cancerous prostate, breast and adrenal tissue.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[3]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[4]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Altered Expression	[5]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Altered Expression	[6]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Melanoma-associated antigen 11 (MAGEA11).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Melanoma-associated antigen 11 (MAGEA11).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Melanoma-associated antigen 11 (MAGEA11).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Melanoma-associated antigen 11 (MAGEA11).	[8]

References

• [1] DNA methylation and nucleosome occupancy regulate the cancer germline antigen gene MAGEA11.Epigenetics. 2013 Aug;8(8):849-63. doi: 10.4161/epi.25500. Epub 2013 Jul 9.
• [2] Delayed endometrial decidualisation in polycystic ovary syndrome; the role of AR-MAGEA11.J Mol Med (Berl). 2019 Sep;97(9):1315-1327. doi: 10.1007/s00109-019-01809-6. Epub 2019 Jun 29.
• [3] Functional interaction between co-expressed MAGE-A proteins.PLoS One. 2017 May 24;12(5):e0178370. doi: 10.1371/journal.pone.0178370. eCollection 2017.
• [4] Increased expression of androgen receptor coregulator MAGE-11 in prostate cancer by DNA hypomethylation and cyclic AMP.Mol Cancer Res. 2009 Apr;7(4):523-35. doi: 10.1158/1541-7786.MCR-08-0400.
• [5] Expression and Prognostic Relevance of GAGE1 and XAGE1 Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma.Curr Mol Med. 2017;17(10):707-717. doi: 10.2174/1566524018666180322162145.
• [6] Evolution of Melanoma Antigen-A11 (MAGEA11) During Primate Phylogeny.J Mol Evol. 2018 Apr;86(3-4):240-253. doi: 10.1007/s00239-018-9838-8. Epub 2018 Mar 24.
• [7] 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.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.