Proteasome subunit beta type-8 (PSMB8)
The protein contains 276 amino acids for an estimated molecular weight of 30354 Da.
The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119). Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes. (updated: June 5, 2019)
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.
- 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.
- 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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Biological Process
Anaphase-promoting complex-dependent catabolic process
Antigen processing and presentation
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
Cytokine-mediated signaling pathway
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Fat cell differentiation
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 involved in cellular protein catabolic process
Regulation of apoptotic process
Regulation of cellular amino acid metabolic process
Regulation of endopeptidase activity
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
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
Type I interferon signaling pathway
Viral process
Wnt signaling pathway, planar cell polarity pathway
The reference OMIM entry for this protein is 177046
Proteasome subunit, beta-type, 8; psmb8
Large multifunctional protease 7; lmp7
Proteasome-related gene 7
Ring10
Proteasome subunit beta-5i
DESCRIPTION
The immunoproteasome, a distinct class of proteasome found predominantly in monocytes and lymphocytes, shapes the antigenic repertoire presented on major histocompatibility complex (MHC) class I molecules. PSMB8 encodes the chymotrypsin-like catalytic subunit of the immunoproteasome (Muchamuel et al., 2009).GENE STRUCTURE
Agarwal et al. (2010) noted that the PSMB8 gene contains 6 exons with alternative splicing of exons 1A and 1B.MAPPING
Antigen processing involves the generation of peptides from cytosolic proteins and their transport into the endoplasmic reticulum, where they associate with MHC class I molecules. Two genes have been identified in the MHC class II region, TAP1 (170260) and TAP2 (170261), that are thought to encode the peptide transport proteins. Glynne et al. (1991) reported a proteasome-related sequence, RING10, mapping between the transporter genes on chromosome 6p21.3.GENE FUNCTION
Muchamuel et al. (2009) showed that PR-957, a selective inhibitor of LMP7, blocked presentation of MHC class I-restricted antigens in vitro and in vivo. PR-957 also blocked production of IL23 (see 605580) by activated monocytes and IL2 (147680) and IFNG (147570) by T cells. In mouse models, PR-957 reversed signs of rheumatoid arthritis (RA; 180300) and cellular infiltration, cytokine production, and autoantibody levels. Muchamuel et al. (2009) concluded that LMP7 has a role in controlling pathogenic immune responses and may be a target in autoimmune disorders. Incorporation of the proteasome beta subunits into the maturing proteasome frequently requires proteolytic removal of a prosequence by proteolytically active subunits. By following the incorporation of mutant human LMP7 into the 20S proteasome, Witt et al. (2000) showed that the LMP7 prosequence was not essential for incorporation of LMP7 into the maturing proteasome, but it increased the efficiency of LMP7 incorporation and proteasome maturation.MOLECULAR GENETICS
Deng et al. (1995) found evidence suggesting that LMP genes have effects on susceptibility to insulin-dependent diabetes mellitus (IDDM; 222100), independent of HLA-DR and HLA-DQ. A genomic polymorphism of LMP7 was found to be strongly associated with IDDM, and the arg/his-60 polymorphism in LMP2 (309060) was found to be associated with IDDM in subjects containing an HLA-DR4-DQB1*0302 haplotype. By genomewide homozygosity mapping followed by candidate gene sequencing of the 3 patients with autoinflammatory, lipodystrophy, and dermatosis syndrome (ALDD; 256040) reported by Garg et al. (2010), Agarwal et al. (2010) identified the same homozygous mutation in the PSMB8 gene (T75M; 177046.0001). Kitamura et al. (2011) identified a homozygous PSMB8 mutation (G197V; 177046.0002) in 3 Japanese patients from 2 consanguineous families with the Nakajo-Nishimura autoinflammatory syndrome. One of the families had previously been reported by Tanaka et al. (1993). The mutation increased assembly intermediates of immunoproteasomes, resulting in decreased proteasome function and ubiquitin-coupled protein accumulation in patient tissues. In addition, IL6 (147620) was highly expressed and there was reduced expression of PSMB8. In vitro studies showed that downregulation of PSMB8 inhibited the differentiation of murine and human adipocytes in vitro, and injection of siRNA against Psmb8 in mouse skin reduced adipocyte tissue volume. The findings identified PSMB8 as an essen ... More on the omim web site
June 7, 2019: 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 177046 was added.