InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PSMB8

Summary

InnateDB Protein

IDBP-81526.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PSMB8

Protein Name

proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7)

Synonyms

ALDD; D6S216; D6S216E; JMP; LMP7; NKJO; PSMB5i; RING10;

Species

Homo sapiens

Ensembl Protein

ENSP00000364015

InnateDB Gene

IDBG-81522 (PSMB8)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000269PubMed:16423992, ECO:0000269PubMed:19443843, ECO:0000269PubMed:21881205, ECO:0000269PubMed:8163024}.

Subcellular Localization

Cytoplasm {ECO:0000255PROSITE- ProRule:PRU00809}. Nucleus {ECO:0000250}.

Disease Associations

Nakajo syndrome (NKJO) [MIM:256040]: An autosomal recessive autoinflammatory disorder characterized by early childhood onset of recurrent fever, joint stiffness and severe contractures of the hands and feet, and erythematous skin lesions with subsequent development of lipodystrophy and laboratory evidence of immune dysregulation. Accompanying features may include muscle weakness and atrophy, hepatosplenomegaly, and microcytic anemia. {ECO:0000269PubMed:21129723, ECO:0000269PubMed:21852578, ECO:0000269PubMed:21881205}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Mutation Met-75 has been found in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE syndrome). CANDLE patients have some overlapping features with NKJO patients, including a cutaneous eruption and lipodystrophy. They show a characteristic neutrophilic dermatosis with a mononuclear interstitial infiltrate in the dermis that seems pathognomonic for CANDLE syndrome (PubMed:21953331). {ECO:0000269PubMed:21953331}.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 56 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	56 [view]
Protein-Protein	53 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004298	threonine-type endopeptidase activity
GO:0005515	protein binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0000209	protein polyubiquitination
GO:0000278	mitotic cell cycle
GO:0002474	antigen processing and presentation of peptide antigen via MHC class I
GO:0002479	antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
GO:0006521	regulation of cellular amino acid metabolic process
GO:0006915	apoptotic process
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0010467	gene expression
GO:0016032	viral process
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0019221	cytokine-mediated signaling pathway
GO:0031145	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0034641	cellular nitrogen compound metabolic process
GO:0042590	antigen processing and presentation of exogenous peptide antigen via MHC class I
GO:0042981	regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0044281	small molecule metabolic process
GO:0045444	fat cell differentiation
GO:0051436	negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051437	positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051439	regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051603	proteolysis involved in cellular protein catabolic process
GO:0060337	type I interferon signaling pathway

Cellular Component

GO:0000502	proteasome complex
GO:0005654	nucleoplasm
GO:0005829	cytosol
GO:0005839	proteasome core complex
GO:0070062	extracellular vesicular exosome
GO:1990111	spermatoproteasome complex