Proteasome subunit beta type-5 (PSMB5)
The protein contains 263 amino acids for an estimated molecular weight of 28480 Da.
Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity. (updated: Jan. 31, 2018)
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.
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| Variant | Description |
|---|---|
| dbSNP:rs11543947 |
Biological Process
Anaphase-promoting complex-dependent catabolic process
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
Post-translational protein modification
Pre-replicative complex assembly
Proteasomal protein catabolic process
Proteasomal ubiquitin-independent protein catabolic process
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein deubiquitination
Protein polyubiquitination
Proteolysis
Regulation of apoptotic process
Regulation of cellular amino acid metabolic process
Regulation of hematopoietic stem cell differentiation
Regulation of mitotic cell cycle phase transition
Regulation of mRNA stability
Regulation of transcription from RNA polymerase II promoter in response to hypoxia
Response to oxidative stress
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
The reference OMIM entry for this protein is 600306
Proteasome subunit, beta-type, 5; psmb5
Proteasome subunit x
Psx large multifunctional protease x; lmpx
Proteasome subunit beta-5
DESCRIPTION
Proteasomes are the proteolytic complex responsible for major histocompatibility complex (MHC) class I-restricted antigen presentation (Akiyama et al., 1994). See PSMB2 (602175) for further discussion of beta-type proteasome subunits.CLONING
Akiyama et al. (1994) cloned the full-length cDNA and showed that PSMB5 has high amino acid similarity to PSMB8 (177046).GENE FUNCTION
Akiyama et al. (1994) showed that treatment with interferon-gamma (IFNG; 147570) increased expression of MHC-encoded LMP2 (PSMB9; 177045) and LMP7 (PSMB8; 177046) subunits of the proteasome and decreased expression of 2 proteasomal subunits PSMB5 and PSMB6, which altered the proteolytic specificity of proteasomes. IFNG may induce subunit replacements of PSMB5 and PSMB6, producing proteasomes that may be more appropriate for the immunologic processing of endogenous antigens. Bortezomib, a reversible proteasome inhibitor used in the treatment of refractory multiple myeloma (see 254500), targets primarily the chymotrypsin-like activity of PSMB5. To study the molecular basis of bortezomib resistance, Oerlemans et al. (2008) generated high levels of acquired resistance in human myelomonocytic THP1 cells by exposure to stepwise increasing concentrations of bortezomib. Analysis of resistant cells revealed that those with higher levels of resistance were homozygous for a missense mutation in the highly conserved substrate/inhibitory binding domain of PSMB5. In addition, there was dramatic overexpression of PSM5B protein, but not of other proteasome subunits. RNAi-mediated silencing of PSMB5 expression resulted in restoration of bortezomib sensitivity in resistant cells. Oerlemans et al. (2008) concluded that bortezomib resistance is associated with selective overexpression of a mutant PSMB5 protein.MAPPING
The PSMB5 gene was mapped to chromosome 14q11.2 by Belich et al. (1994). McCusker et al. (1997) demonstrated that the PSMB5 gene is located on 14q11.2 within 1 Mb of the genes encoding the alpha (600654) and beta (602161) subunits of the PA28 complex. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 600306 was added.