PSMB8
Developmental stage
Highly expressed in immature dendritic cells (at protein level).
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 (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.
Involvement in disease
Proteasome-associated autoinflammatory syndrome 1
PRAAS1
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.
Sequence Similarities
Belongs to the peptidase T1B family.
Cellular localization
- Cytoplasm
- Nucleus
Alternative names
LMP7, PSMB5i, RING10, Y2, PSMB8, Proteasome subunit beta type-8, Low molecular mass protein 7, Macropain subunit C13, Multicatalytic endopeptidase complex subunit C13, Proteasome component C13, Proteasome subunit beta-5i, Really interesting new gene 10 protein