Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOQQO2X)

• DOT Name: Melanoma-associated antigen E1 (MAGEE1)
• Synonyms: Alpha-dystrobrevin-associated MAGE Protein; DAMAGE; Hepatocellular carcinoma-associated protein 1; MAGE-E1 antigen
• Gene Name: MAGEE1
• Related Disease:
  Infantile malignant osteopetrosis
  Advanced cancer
  Alzheimer disease
  Bile duct disease
  Bipolar disorder
  Colon carcinoma
  Disorder of orbital region
  Epilepsy
  Glaucoma/ocular hypertension
  Hepatocellular carcinoma
  Melanoma
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
  Amyotrophic lateral sclerosis
  Rheumatoid arthritis
• UniProt ID: MAGE1_HUMAN
• Pfam ID: PF01454
• Sequence:
  MSLVSQNSRRRRRRVAKATAHNSSWGEMQAPNAPGLPADVPGSDVPQGPSDSQILQGLCA
  SEGPSTSVLPTSAEGPSTFVPPTISEASSASGQPTISEGPGTSVLPTPSEGLSTSGPPTI
  SKGLCTSVTLAASEGRNTSRPPTSSEEPSTSVPPTASEVPSTSLPPTPGEGTSTSVPPTA
  YEGPSTSVVPTPDEGPSTSVLPTPGEGPGTSVPLAATEGLSTSVQATPDEGPSTSVPPTA
  TEGLSTPVPPTRDEGPSTSVPATPGEGPSTSVLPAASDGQSISLVPTRGKGSSTSVPPTA
  TEGLSTSVQPTAGEGSSTSVPPTPGGGLSTSVPPTATEELSTSVPPTPGEGPSTSVLPIP
  GEGLSTSVPPTASDGSDTSVPPTPGEGASTLVQPTAPDGPGSSVLPNPGEGPSTLFSSSA
  SVDRNPSKCSLVLPSPRVTKASVDSDSEGPKGAEGPIEFEVLRDCESPNSISIMGLNTSR
  VAITLKPQDPMEQNVAELLQFLLVKDQSKYPIRESEMREYIVKEYRNQFPEILRRAAAHL
  ECIFRFELRELDPEAHTYILLNKLGPVPFEGLEESPNGPKMGLLMMILGQIFLNGNQAKE
  AEIWEMLWRMGVQRERRLSIFGNPKRLLSVEFVWQRYLDYRPVTDCKPVEYEFFWGPRSH
  LETTKMKILKFMAKIYNKDPMDWPEKYNEALEEDAARAFAEGWQALPHFRRPFFEEAAAE
  VPSPDSEVSSYSSKYAPHSWPESRLESKARKLVQLFLLMDSTKLPIPKKGILYYIGRECS
  KVFPDLLNRAARTLNHVYGTELVVLDPRNHSYTLYNRREMEETEEIVDSPNRPGNNFLMQ
  VLSFIFIMGNHARESAVWAFLRGLGVQAGRKHVITCRYLSQRYIDSLRVPDSDPVQYEFV
  WGPRARLETSKMKALRYVARIHRKEPQDWPQQYREAMEDEANRADVGHRQIFVHNFR
• Function: May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Infantile malignant osteopetrosis	DIS8C3LZ	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Bile duct disease	DISPFUV2	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Disorder of orbital region	DISH0ECJ	Strong	Biomarker	[7]
Epilepsy	DISBB28L	Strong	Biomarker	[2]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Melanoma	DIS1RRCY	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[10]
Obesity	DIS47Y1K	moderate	Biomarker	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[11]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Melanoma-associated antigen E1 (MAGEE1).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Melanoma-associated antigen E1 (MAGEE1).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Melanoma-associated antigen E1 (MAGEE1).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Melanoma-associated antigen E1 (MAGEE1).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Melanoma-associated antigen E1 (MAGEE1).	[17]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Melanoma-associated antigen E1 (MAGEE1).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Melanoma-associated antigen E1 (MAGEE1).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Melanoma-associated antigen E1 (MAGEE1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Melanoma-associated antigen E1 (MAGEE1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Melanoma-associated antigen E1 (MAGEE1).	[23]

1 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 E1 (MAGEE1).	[19]

References

• [1] The determination of osteopetrotic phenotypes by selective inactivation of red cell carbonic anhydrase isoenzymes.Clin Chim Acta. 1985 Nov 15;152(3):347-54. doi: 10.1016/0009-8981(85)90110-x.
• [2] Design, synthesis and biological evaluation of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as potent carbonic anhydrase IX inhibitors.Bioorg Chem. 2019 Feb;82:117-122. doi: 10.1016/j.bioorg.2018.10.005. Epub 2018 Oct 5.
• [3] Novel sulfamate derivatives of menthol: Synthesis, characterization, and cholinesterases and carbonic anhydrase enzymes inhibition properties.Arch Pharm (Weinheim). 2018 Nov;351(11):e1800209. doi: 10.1002/ardp.201800209. Epub 2018 Sep 26.
• [4] Embracing the Dark Side: Computational Approaches to Unveil the Functionality of Genes Lacking Biological Annotation in Drug-Induced Liver Injury.Front Genet. 2018 Nov 20;9:527. doi: 10.3389/fgene.2018.00527. eCollection 2018.
• [5] Increased DNA and RNA damage by oxidation in patients with bipolar I disorder.Transl Psychiatry. 2016 Aug 9;6(8):e867. doi: 10.1038/tp.2016.141.
• [6] Enhancement of radiation-induced DNA double-strand breaks and micronuclei in human colon carcinoma cells by N-methylformamide.Radiat Res. 1989 Jul;119(1):166-75.
• [7] Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors.J Enzyme Inhib Med Chem. 2017 Dec;32(1):1274-1281. doi: 10.1080/14756366.2017.1380638.
• [8] Antitumor activity of an adenovirus harboring human IL-24 in colon cancer.Mol Biol Rep. 2011 Jan;38(1):395-401. doi: 10.1007/s11033-010-0121-3. Epub 2010 Mar 31.
• [9] Direct and straightforward access to substituted alkyl selenols as novel carbonic anhydrase inhibitors.Eur J Med Chem. 2020 Jan 1;185:111811. doi: 10.1016/j.ejmech.2019.111811. Epub 2019 Oct 30.
• [10] Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study.Eur J Hum Genet. 2009 Aug;17(8):1056-62. doi: 10.1038/ejhg.2009.4. Epub 2009 Feb 11.
• [11] Synthesis and human/bacterial carbonic anhydrase inhibition with a series of sulfonamides incorporating phthalimido moieties.Bioorg Med Chem. 2017 Apr 15;25(8):2524-2529. doi: 10.1016/j.bmc.2017.03.017. Epub 2017 Mar 9.
• [12] Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort).Arthritis Rheum. 2006 Apr;54(4):1122-31. doi: 10.1002/art.21749.
• [13] 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.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [16] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [17] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] 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.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [22] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.