Alternative titles; symbols
HGNC Approved Gene Symbol: MAGED1
Cytogenetic location: Xp11.22 Genomic coordinates (GRCh38): X:51,803,076-51,902,354 (from NCBI)
Expression of members of several tumor-associated antigen families, of which the MAGE family (see 300016) is an example, is restricted to tumor cells and testis. Pold et al. (1999) used representational difference analysis to identify differences in gene expression in bone marrow stromal cells from multiple myeloma patients compared to that in cells from healthy marrow donors. They cloned a new member of the MAGE family, MAGED1. The deduced 574-amino acid protein shows strong homology to members of the MAGE gene family at its C terminus. RT-PCR showed that MAGED1 is expressed in bone marrow stromal cells from both multiple myeloma patients and healthy donors. RT-PCR and Northern blot analysis of healthy adult tissues showed expression of MAGED1 in all tissues examined, in contrast to the expression pattern of other members of this family.
Kubu et al. (2000) determined the nucleotide sequence 5-prime of the MAGED1 start codon reported by Pold et al. (1999) from a placenta-derived clone and showed that the initial methionine is located 204 amino acids before that previously reported. The 778-amino acid protein is 88% identical to the rat protein. Western blot analysis indicated that rat Maged1 was expressed as a 90-kD myc-HIS-tagged protein in COS cells.
Using yeast 2-hybrid analysis of a mouse cDNA library with the rat p75(Ntr) (NGFR; 162010) intracellular domain as bait, followed by screening a rat neural crest cDNA library and searching a sequence database, Salehi et al. (2000) obtained cDNAs encoding rat and human NRAGE. Sequence analysis predicted that the 778-amino acid human NRAGE protein contains a 200-amino acid MAGE homology domain. Northern blot analysis detected a 3.0-kb transcript in rat tissue. In vitro pull-down and coimmunoprecipitation analyses confirmed the interaction of NRAGE and p75(NTR). Whole-mount in situ hybridization analysis showed low-level expression of Nrage throughout embryonic day-11.5 (E11.5) rat embryos. Western blot analysis detected expression in E18 embryos that was highest in cerebral cortex and cerebellum. By adulthood, however, expression was detectable only in lung and cortex. Double-label immunocytochemistry demonstrated coexpression of p75(Ntr) and Nrage in marginal zones of E14 medulla oblongata. Immunoblot analysis showed that Nrage expression shifts from the cytosol to the plasma membrane upon stimulation of cells with nerve growth factor (NGF; 162030). Coimmunoprecipitation analysis indicated that in the presence of Nrage, p75(Ntr) and TrkA (191315) lose the ability to interact. Immunofluorescence microscopy showed that NRAGE overexpression strongly retards cell cycle progression. Immunoblot analysis indicated that coexpression of Nrage and p75(Ntr), but not Trka, in a sympathoadrenal progenitor cell line led to apoptosis after exposure to NGF but not after exposure to BDNF (113505) or NTF3 (162660). Salehi et al. (2000) concluded that NRAGE is part of an NGF-specific p75(NTR) apoptotic signaling cascade in sympathoadrenal and neuronal cells and that the apoptotic effect of NRAGE is antagonized by TRKA.
Pold et al. (1999) mapped the MAGED1 gene to Xp11.23 by analysis of radiation hybrid panels.
See 300016 for a discussion of the high frequency of genes on the X chromosome encoding proteins with the MAGE domain as well as other cancer-testis antigen genes (Ross et al., 2005).
Kubu, C. J., Goldhawk, D. G., Barker, P. A., Verdi, J. M. Identification of the translational initiation codon in human MAGED1. (Letter) Genomics 70: 150-152, 2000. [PubMed: 11087672] [Full Text: https://doi.org/10.1006/geno.2000.6356]
Pold, M., Zhou, J., Chen, G. L., Hall, J. M., Vescio, R. A., Berenson, J. R. Identification of a new, unorthodox member of the MAGE gene family. Genomics 59: 161-167, 1999. [PubMed: 10409427] [Full Text: https://doi.org/10.1006/geno.1999.5870]
Ross, M. T., Grafham, D. V., Coffey, A. J., Scherer, S., McLay, K., Muzny, D., Platzer, M., Howell, G. R., Burrows, C., Bird, C. P., Frankish, A., Lovell, F. L., and 270 others. The DNA sequence of the human X chromosome. Nature 434: 325-337, 2005. [PubMed: 15772651] [Full Text: https://doi.org/10.1038/nature03440]
Salehi, A. H., Roux, P. P., Kubu, C. J., Zeindler, C., Bhakar, A., Tannis, L.-L., Verdi, J. M., Barker, P. A. NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis. Neuron 27: 279-288, 2000. [PubMed: 10985348] [Full Text: https://doi.org/10.1016/s0896-6273(00)00036-2]