MAGED1 explained

Melanoma-associated antigen D1 is a protein that in humans is encoded by the MAGED1 gene.^[1]

Function

This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different isoforms have been found for this gene.^[2]

MAGED was found to be deleted in a group of children with an intellectual disability disorder caused by a Xp11.22 deletion.^[3]

Maged1 plays a role in controlling the reward circuitry in the brain of mice that is responsible for addictive behaviors.^[4] More recently, it has been shown to play a role in drug addiction through an epigenetic mechanism involving the monoubiquitination of H2A, which represses gene expression via interaction with the deubiquitinase USP7.^[5]

Interactions

MAGED1 has been shown to interact with UNC5A,^[6] PJA1,^[7] XIAP,^[8] and USP7.

Further reading

• Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA . NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis . Neuron . 27 . 2 . 279–88 . 2000 . 10985348 . 10.1016/S0896-6273(00)00036-2 . free .
• Masuda Y, Sasaki A, Shibuya H, Ueno N, Ikeda K, Watanabe K . Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function . J. Biol. Chem. . 276 . 7 . 5331–8 . 2001 . 11084035 . 10.1074/jbc.M008590200 . free .
• Kubu CJ, Goldhawk DG, Barker PA, Verdi JM . Identification of the translational initiation codon in human MAGED1 . Genomics . 70 . 1 . 150–2 . 2001 . 11087672 . 10.1006/geno.2000.6356 .
• Zhang CG, Xing GC, Wei HD, Yu YT, He FC . [A new melanoma antigen-encoding gene subfamily in human chromosome X] . Yi Chuan Xue Bao . 28 . 3 . 197–203 . 2001 . 11280991 .
• Stone B, Schummer M, Paley PJ, Crawford M, Ford M, Urban N, Nelson BH . MAGE-F1, a novel ubiquitously expressed member of the MAGE superfamily . Gene . 267 . 2 . 173–82 . 2001 . 11313144 . 10.1016/S0378-1119(01)00406-1 .
• Jordan BW, Dinev D, LeMellay V, Troppmair J, Gotz R, Wixler L, Sendtner M, Ludwig S, Rapp UR . Neurotrophin receptor-interacting mage homologue is an inducible inhibitor of apoptosis protein-interacting protein that augments cell death . J. Biol. Chem. . 276 . 43 . 39985–9 . 2001 . 11546791 . 10.1074/jbc.C100171200 . free .
• Sasaki A, Masuda Y, Iwai K, Ikeda K, Watanabe K . A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1 . J. Biol. Chem. . 277 . 25 . 22541–6 . 2002 . 11959851 . 10.1074/jbc.M109728200 . free .
• Xu YC, Wu RF, Gu Y, Yang YS, Yang MC, Nwariaku FE, Terada LS . Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase . J. Biol. Chem. . 277 . 31 . 28051–7 . 2002 . 12023963 . 10.1074/jbc.M202665200 . free .
• Kendall SE, Goldhawk DE, Kubu C, Barker PA, Verdi JM . Expression analysis of a novel p75(NTR) signaling protein, which regulates cell cycle progression and apoptosis . Mech. Dev. . 117 . 1–2 . 187–200 . 2003 . 12204258 . 10.1016/S0925-4773(02)00204-6 . 8919247 .
• Williams ME, Strickland P, Watanabe K, Hinck L . UNC5H1 induces apoptosis via its juxtamembrane region through an interaction with NRAGE . J. Biol. Chem. . 278 . 19 . 17483–90 . 2003 . 12598531 . 10.1074/jbc.M300415200 . free .
• Matsuda T, Suzuki H, Oishi I, Kani S, Kuroda Y, Komori T, Sasaki A, Watanabe K, Minami Y . The receptor tyrosine kinase Ror2 associates with the melanoma-associated antigen (MAGE) family protein Dlxin-1 and regulates its intracellular distribution . J. Biol. Chem. . 278 . 31 . 29057–64 . 2003 . 12754255 . 10.1074/jbc.M302199200 . free .
• Wen CJ, Xue B, Qin WX, Yu M, Zhang MY, Zhao DH, Gao X, Gu JR, Li CJ . hNRAGE, a human neurotrophin receptor interacting MAGE homologue, regulates p53 transcriptional activity and inhibits cell proliferation . FEBS Lett. . 564 . 1–2 . 171–6 . 2004 . 15094062 . 10.1016/S0014-5793(04)00353-9 . 39965080 .
• Bertrand M, Huijbers I, Chomez P, De Backer O . Comparative expression analysis of the MAGED genes during embryogenesis and brain development . Dev. Dyn. . 230 . 2 . 325–34 . 2005 . 15162511 . 10.1002/dvdy.20026 . free .
• Tian XX, Rai D, Li J, Zou C, Bai Y, Wazer D, Band V, Gao Q . BRCA2 suppresses cell proliferation via stabilizing MAGE-D1 . Cancer Res. . 65 . 11 . 4747–53 . 2005 . 15930293 . 3295243 . 10.1158/0008-5472.CAN-05-0018 .
• Xue B, Wen C, Shi Y, Zhao D, Li C . Human NRAGE disrupts E-cadherin/beta-catenin regulated homotypic cell-cell adhesion . Biochem. Biophys. Res. Commun. . 336 . 1 . 247–51 . 2005 . 16125672 . 10.1016/j.bbrc.2005.08.069 .
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . free .

Notes and References

1. Põld M, Zhou J, Chen GL, Hall JM, Vescio RA, Berenson JR . Identification of a new, unorthodox member of the MAGE gene family . Genomics . 59 . 2 . 161–7 . Sep 1999 . 10409427 . 10.1006/geno.1999.5870 .
2. Web site: Entrez Gene: MAGED1 melanoma antigen family D, 1.
3. Grau C, Starkovich M, Azamian MS, Xia F, Cheung SW, Evans P, Henderson A, Lalani SR, Scott DA . Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability . PLOS ONE . 12 . 4 . e0175962 . 2017 . 28414775 . 5393878 . 10.1371/journal.pone.0175962 . 2017PLoSO..1275962G . free .
4. De Backer JF, Monlezun S, Detraux B, Gazan A, Vanopdenbosch L, Cheron J, Cannazza G, Valverde S, Cantacorps L, Nassar M, Venance L, Valverde O, Faure P, Zoli M, De Backer O, Gall D, Schiffmann SN, de Kerchove d'Exaerde A . Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine . EMBO Reports . 19. 9. e45089. July 2018 . 30002119 . 10.15252/embr.201745089 . 6123657 .
5. Cheron J, Beccari L, Hagué P, Icick R, Despontin C, Carusone T, Defrance M, Bhogaraju S, Martin-Garcia E, Capellan R, Maldonado R, Vorspan F, Bonnefont J, de Kerchove d'Exaerde A . USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder . Nature Communications . 14 . 1 . 8481 . December 2023 . 38123574 . 10733359 . 10.1038/s41467-023-44120-2 .
6. Williams ME, Strickland P, Watanabe K, Hinck L . UNC5H1 induces apoptosis via its juxtamembrane region through an interaction with NRAGE . J. Biol. Chem. . 278 . 19 . 17483–90 . May 2003 . 12598531 . 10.1074/jbc.M300415200 . free .
7. Sasaki A, Masuda Y, Iwai K, Ikeda K, Watanabe K . A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1 . J. Biol. Chem. . 277 . 25 . 22541–6 . Jun 2002 . 11959851 . 10.1074/jbc.M109728200 . free .
8. Jordan BW, Dinev D, LeMellay V, Troppmair J, Gotz R, Wixler L, Sendtner M, Ludwig S, Rapp UR . Neurotrophin receptor-interacting mage homologue is an inducible inhibitor of apoptosis protein-interacting protein that augments cell death . J. Biol. Chem. . 276 . 43 . 39985–9 . Oct 2001 . 11546791 . 10.1074/jbc.C100171200 . free .