Alternative titles; symbols
HGNC Approved Gene Symbol: PSME2
Cytogenetic location: 14q12 Genomic coordinates (GRCh38): 14:24,143,365-24,146,610 (from NCBI)
The PA28 complex is an alternative proteasome activator that does not employ the use of ubiquitin. The complex is composed of 2 homologous subunits, PA28-alpha (PSME1; 600654) and PA28-beta (PSME2; 602161), which form a hexameric ring. The PA28 complex is expressed constitutively in antigen-presenting cells. Its expression is upregulated by gamma-interferon (147570), and it appears to be involved in the presentation of endogenous antigens by MHC class I molecules (summary by McCusker et al., 1999).
Ahn et al. (1995) reported the sequence of the human PA28-beta (PSME2) gene and those of rat Pa28-alpha and -beta. The deduced 239-amino acid human PA28-beta protein has a calculated molecular mass of 27.1 kD. It shares 89% amino acid identity with rat Pa28-beta.
McCusker et al. (1999) sequenced the PSME1 and PSME2 genes. Both genes contain 11 exons, consistent with gene duplication during vertebrate evolution. The intron/exon organization of the genes is highly conserved, the major difference being the absence of the exon encoding the lysine and glutamic acid-rich KEKE motif in the gene product of the PSME2 gene.
By fluorescence in situ hybridization, McCusker et al. (1997) showed that the PSME1 and PSME2 genes lie within 30 to 40 kb of each other on chromosome 14q11.2.
In vitro, PA28 binds and activates proteasomes. Preckel et al. (1999) demonstrated that mice with a disrupted Pa28b gene lack Pa28a (Psme1) and Pa28b polypeptides, demonstrating that Pa28 functions as a heterooligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in Pa28 -/- mice. Cytotoxic T-lymphocyte responses are impaired and assembly of immunoproteasomes is greatly inhibited in mice lacking Pa28. These results showed that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.
Ahn, J. Y., Tanahashi, N., Akiyama, K., Hisamatsu, H., Noda, C., Tanaka, K., Chung, C. H., Shibmara, N., Willy, P. J., Mott, J. D., Slaughter, C. A., DeMartino, G. N. Primary structures of two homologous subunits of PA28, a gamma-interferon-inducible protein activator of the 2OS proteasome. FEBS Lett. 366: 37-42, 1995. [PubMed: 7789512] [Full Text: https://doi.org/10.1016/0014-5793(95)00492-r]
McCusker, D., Jones, T., Sheer, D., Trowsdale, J. Genetic relationships of the genes encoding the human proteasome beta subunits and the proteasome PA28 complex. Genomics 45: 362-367, 1997. [PubMed: 9344661] [Full Text: https://doi.org/10.1006/geno.1997.4948]
McCusker, D., Wilson, M., Trowsdale, J. Organization of the genes encoding the human proteasome activators PA28-alpha and beta. Immunogenetics 49: 438-445, 1999. [PubMed: 10199920] [Full Text: https://doi.org/10.1007/s002510050517]
Preckel, T., Fung-Leung, W.-P., Cai, Z., Vitiello, A., Salter-Cid, L., Winqvist, O., Wolfe, T. G., Von Herrath, M., Angulo, A., Ghazal, P., Lee, J.-D., Fourie, A. M., Wu, Y., Pang, J., Ngo, K., Peterson, P. A., Fruh, K., Yang, Y. Impaired immunoproteasome assembly and immune responses in PA28 -/- mice. Science 286: 2162-2165, 1999. [PubMed: 10591649] [Full Text: https://doi.org/10.1126/science.286.5447.2162]