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MGP002483

UniProt Annotations

Entry Information
Gene Nameproteasome (prosome, macropain) subunit, beta type, 8
Protein EntryPSB8_HUMAN
UniProt IDP28062
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Comment=Additional isoforms seem to exist.; Name=1; Synonyms=LMP7B, LMP7-E2; IsoId=P28062-1; Sequence=Displayed; Name=2; Synonyms=LMP7A, LMP7-E1; IsoId=P28062-2; Sequence=VSP_005287; Note=Contains a phosphothreonine at position 5.;
Catalytic ActivityCleavage of peptide bonds with very broad specificity.
Developmental StageHighly expressed in immature dendritic cells (at protein level). {ECO:0000269|PubMed:11717192}.
DiseaseNakajo 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:0000269|PubMed:21129723, ECO:0000269|PubMed:21852578, ECO:0000269|PubMed:21881205}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNote=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:0000269|PubMed:21953331}.
FunctionThe 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:0000269|PubMed:16423992, ECO:0000269|PubMed:19443843, ECO:0000269|PubMed:21881205, ECO:0000269|PubMed:8163024}.
InductionUp-regulated by IFNG/IFN-gamma and IRF1 (at protein level). Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Down-regulated by the selective inhibitor PR-957. Down-regulated in mature dendritic cells by HSV-1 infection. Up- regulated by heat shock treatment. {ECO:0000269|PubMed:11493458, ECO:0000269|PubMed:15501285, ECO:0000269|PubMed:15907481, ECO:0000269|PubMed:17142736, ECO:0000269|PubMed:17262812, ECO:0000269|PubMed:19443843, ECO:0000269|PubMed:19525961, ECO:0000269|PubMed:19619915, ECO:0000269|PubMed:8663318}.
InteractionP27958:- (xeno); NbExp=4; IntAct=EBI-372294, EBI-3649474;
PtmAutocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity. {ECO:0000250|UniProtKB:O35955}.
SimilarityBelongs to the peptidase T1B family. {ECO:0000255|PROSITE-ProRule:PRU00809}.
Subcellular LocationCytoplasm {ECO:0000255|PROSITE- ProRule:PRU00809}. Nucleus {ECO:0000250}.
SubunitThe 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB5. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Directly interacts with POMP. Interacts with HIV-1 TAT protein. Interacts with TAP1. {ECO:0000269|PubMed:14550573, ECO:0000269|PubMed:15488952, ECO:0000269|PubMed:15944226}.
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