Proteasome subunit beta type-8
Also known as: LMP7, PSMB5i, PSMB8, RING10, Y2
Function
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. 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.
Classification
- Family (Pfam)
- PF00227 Proteasome
- InterPro
- Ntn_hydrolases_N, Pept_T1A_subB, Proteasome_bsu_CS, Proteasome_sua/b, Proteasome_suB-type
- Functional cluster
- Tubulins & Mitochondrial Metabolic Enzymes
Experimental structures · PDB · 22
- 5L5A X-ray 2.40A
- 5L5B X-ray 2.80A
- 5L5D X-ray 2.80A
- 5L5E X-ray 2.90A
- 5L5F X-ray 2.50A
- 5L5H X-ray 2.60A
- 5L5I X-ray 2.90A
- 5L5J X-ray 2.90A
- 5L5O X-ray 2.60A
- 5L5P X-ray 2.80A
- 5L5Q X-ray 2.80A
- 5L5R X-ray 2.90A
- … and 10 more
A predicted model is available from AlphaFold.
Gene Ontology · 22
- GO:0005829 cytosol
- GO:0070062 extracellular exosome
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0000502 proteasome complex
- GO:0005839 proteasome core complex
- GO:0019774 proteasome core complex, beta-subunit complex
- GO:1990111 spermatoproteasome complex
- GO:0004175 endopeptidase activity
- GO:0004298 threonine-type endopeptidase activity
- GO:0160165 CD8-positive, alpha-beta T cell homeostasis
- GO:0045444 fat cell differentiation
- GO:0002376 immune system process
- GO:0045590 negative regulation of regulatory T cell differentiation
- GO:0032743 positive regulation of interleukin-2 production
- GO:0032760 positive regulation of tumor necrosis factor production
- GO:0032729 positive regulation of type II interferon production
- GO:0010498 proteasomal protein catabolic process
- GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
- GO:0034341 response to type II interferon
- GO:0045063 T-helper 1 cell differentiation
- GO:0072539 T-helper 17 cell differentiation
Disease associations
- proteasome-associated autoinflammatory syndrome 1 MONDO:0054698
Drugs targeting this protein · 7
- OPROZOMIB inhibitor
- IXAZOMIB inhibitor
- BORTEZOMIB inhibitor
- IXAZOMIB CITRATE inhibitor
- MARIZOMIB inhibitor
- CARFILZOMIB inhibitor
- BORTEZOMIB D-MANNITOL inhibitor
Related proteins · sequence + function similarity
- Proteasome subunit beta type-8 0.99
- Proteasome subunit beta type-8 0.98
- Proteasome subunit beta type-8 0.97
- Proteasome subunit beta type-8 0.95
- Proteasome subunit beta type-5 0.94
- Proteasome subunit beta type-5 0.93
- Proteasome subunit beta type-5 0.90
- Proteasome subunit beta type-5 0.90
- Proteasome subunit beta type-5 0.89
- Proteasome subunit beta type-6 0.88
- Proteasome subunit beta type-9 0.87
- Probable proteasome subunit beta type-5 0.87
Co-cited proteins · studied together in the literature
- Proteasome subunit beta type-9 15 shared papers
- Proteasome subunit beta type-8 5 shared papers
- Proteasome subunit beta type-10 6 shared papers
- Proteasome maturation protein 3 shared papers
- Proteasome subunit beta type-5 5 shared papers
- Proteasome subunit beta type-9 2 shared papers
- HLA class II histocompatibility antigen, DO beta chain 2 shared papers
- HLA class I histocompatibility antigen, A alpha chain 1 shared papers
- Antigen peptide transporter 1 3 shared papers
- Proteasome subunit beta type-4 3 shared papers
- ATP-dependent translocase ABCB1 1 shared papers
- Interferon gamma 1 shared papers
Literature · 36 cited papers
- Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes. Sci. Rep. · 2016
- PMID 26829627 J. Clin. Invest. · 2016
- CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature-a rare case with a novel mutation. Eur. J. Pediatr. · 2016
- Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J. Clin. Invest. · 2015
- N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Mutations in proteasome subunit beta type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. · 2012
- A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans. J. Clin. Invest. · 2011
- Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome. Proc. Natl. Acad. Sci. U.S.A. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- PSMB8 encoding the beta5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndrome. Am. J. Hum. Genet. · 2010
- Herpes simplex virus type I infection of mature dendritic cells leads to reduced LMP7-mRNA-expression levels. Immunobiology · 2009
- … and 24 more in the literature graph