Proteasome activator complex subunit 1 (PSME1)
The protein contains 249 amino acids for an estimated molecular weight of 28723 Da.
Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
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| Variant | Description |
|---|---|
| dbSNP:rs1803830 | |
| dbSNP:rs14930 |
Biological Process
Anaphase-promoting complex-dependent catabolic process
Antigen processing and presentation of exogenous antigen
Antigen processing and presentation of exogenous peptide antigen via MHC class I
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
Antigen processing and presentation of peptide antigen via MHC class I
Apoptotic process
Cellular nitrogen compound metabolic process
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Fc-epsilon receptor signaling pathway
G1/S transition of mitotic cell cycle
Gene expression
Interleukin-1-mediated signaling pathway
MAPK cascade
Mitotic cell cycle
Negative regulation of apoptotic process
Negative regulation of canonical Wnt signaling pathway
Negative regulation of G2/M transition of mitotic cell cycle
NIK/NF-kappaB signaling
Obsolete negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Obsolete positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition
Obsolete regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Positive regulation of canonical Wnt signaling pathway
Positive regulation of endopeptidase activity
Post-translational protein modification
Pre-replicative complex assembly
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein deubiquitination
Protein polyubiquitination
Regulation of apoptotic process
Regulation of cellular amino acid metabolic process
Regulation of G1/S transition of mitotic cell cycle
Regulation of hematopoietic stem cell differentiation
Regulation of mitotic cell cycle phase transition
Regulation of mRNA stability
Regulation of proteasomal protein catabolic process
Regulation of transcription from RNA polymerase II promoter in response to hypoxia
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Small molecule metabolic process
Stimulatory C-type lectin receptor signaling pathway
T cell receptor signaling pathway
Transmembrane transport
Tumor necrosis factor-mediated signaling pathway
Viral process
Wnt signaling pathway, planar cell polarity pathway
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Nucleoplasm
Proteasome activator complex
Proteasome complex
The reference OMIM entry for this protein is 600654
Proteasome activator subunit 1; psme1
Proteasome activator 28-alpha
Pa28-alpha; pa28a
Interferon-gamma-inducible protein 5111; ifi5111
Mcp activator, 29-kd subunit
DESCRIPTION
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) 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).CLONING
Honore et al. (1993) isolated a cDNA from a fibroblast library that encoded a protein, IGUP I-5111, that was upregulated by gamma-interferon. The protein has a predicted molecular mass of 28.7 kD and contains an RGD sequence found in many extracellular glycoprotein ligands of the integrin receptor family. Realini et al. (1994) cloned the identical protein, which they identified as a gamma-interferon-inducible activator of multicatalytic protease (MCP). MCP is an ATP-dependent protease that degrades proteins conjugated to ubiquitin (see 191339). In the presence of ATP, MCP associates with a particle containing at least 15 different polypeptides to form a 26S enzyme. An activator composed of 2 distinct subunits has been isolated from red cells that can stimulate MCP by binding reversibly to it in the absence of nucleotides. The 2 subunits, of 29 kD (PSME1) and 31 kD (PSME2; 602161), are complexed as a hexamer. The predicted PSME1 protein has 249 amino acids and contains KEKE motifs which are also found in 2 MCP subunits and in various chaperonins, including hsp90 (see 140571), hsp70 (see 140550), and calnexin (114217). The recombinantly expressed protein was shown to react with antibodies to the red blood cell activator and had the expected electrophoretic properties. It was also able to bind and activate MCP. As expected from the study by Honore et al. (1993), gamma-interferon treatment of HeLa cells resulted in synthesis of the 29-kD MCP activator.GENE STRUCTURE
McCusker et al. (1999) sequenced the PSME1 and PSME2 genes. They found that each gene contains 11 exons, consistent with gene duplication during vertebrate evolution. The intron/exon organization of the genes was 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.MAPPING
McCusker et al. (1997) demonstrated that the genes encoding the alpha and beta subunits of the PA28 complex are closely linked on 14q11.2, within 1 Mb of the beta proteasome locus PSMB5 (600306). The PSMB5 gene had been mapped to 14q11.2 by Belich et al. (1994). McCusker et al. (1997) used 2-color fluorescence in situ hybridization to determine the relative proximity of PSMB5 and PSME1. The PSME1 and PSME2 genes were found to lie within 30 to 40 kb of each other on band 14q11.2.GENE FUNCTION
In vitro, PA28 binds and activates proteasomes. Preckel et al. (1999) demonstrated that mice with a disrupted Pa28b gene lack Pa28a 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 antige ... More on the omim web site
Subscribe to this protein entry history 
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600654 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed