PROSITE documentation PDOC50838

MAGE conserved domain profile

The first mammalian members of the MAGE (melanoma-associated antigen) gene family were originally described as completely silent in normal adult tissues, with the exception of male germ cells, and, for some of them, placenta. By contrast, these genes were expressed in various kind of tumors. However, other members of the family were recently found to be expressed in normal cells, indicating that the family is larger and more disparate than initially expected. MAGE-like genes have also been identified in non-mammalian species, like the zebrafish or Drosophila melanogaster. Although no MAGE homologous sequences have been identified in Caenorhabditis elegans, Saccharomyces cerevisiae or Schizosaccharomyces pombe, MAGE sequences have been found in several vegetal species, including Arabidopsis thaliana [1].

The only region of homology shared by all of the members of the family is a stretch of about 200 amino acids which has been named the MAGE conserved domain. The MAGE conserved domain is usually located close to the C-termini, although it can also be found in a more central position in some proteins. The MAGE conserved domain is generally present as a single copy but it is duplicated in some proteins. It has been proposed that the MAGE conserved domain of MAGE-D proteins might interact with p75 neurotrophin or related receptors [1].

Proteins known to contain a MAGE domain are listed below:

• Human MAGE-A, -B and -C proteins. MAGE-A, -B and -C genes are silent in all normal tissues with the exception of testis.
• Human MAGE-D to -L proteins. MAGE-D to -L genes are expressed in normal adult tissues.
• Mouse Mage-a and -b proteins.
• Mouse Mage-d, -e, -g, -h, -k and -l.
• Mammalian Necdin. The human Necdin gene is a candidate for the Prader-Willi syndrome.

The profile we developed covers the entire MAGE domain.