PSMB8: Proteasome 20S Subunit Beta 8
A key immunoproteasome subunit involved in antigen processing and inflammatory disorders
Gene Information Card
| Symbol | PSMB8 |
|---|---|
| Full Name | Proteasome 20S Subunit Beta 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.32 |
| NCBI Gene ID | 5696 ncbi.nlm.nih.gov/gene/5696 |
| Ensembl ID | ENSG00000100811 |
| UniProt ID | P28062 |
| OMIM ID | 177046 |
| HGNC ID | 9545 |
| Aliases | LMP7, RING10, PSMB5i, beta1i |
Description
PSMB8 encodes the beta 8 subunit of the 20S proteasome, specifically the immunoproteasome. This subunit replaces the constitutive beta 5 subunit in immunoproteasomes, enhancing the generation of peptides for MHC class I antigen presentation. It is induced by interferon-gamma and plays a critical role in immune surveillance and protein homeostasis. Mutations in PSMB8 cause proteasome-associated autoinflammatory syndromes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Proteasome-associated autoinflammatory syndrome 1 (PRAAS1) / Nakajo-Nishimura syndrome | Loss-of-function mutations impair proteasome assembly and activity, leading to accumulation of ubiquitinated proteins and chronic type I interferon signaling | OMIM #256040 |
| Joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP) syndrome | Same mechanism as PRAAS1; defective immunoproteasome causes interferonopathy | OMIM #256040 |
| Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome | Biallelic PSMB8 mutations disrupt proteasome function, triggering interferon overproduction | ClinVar, OMIM #256040 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 23.4 | High |
| Lymph node | 18.7 | High |
| Bone marrow | 15.2 | High |
| Lung | 10.1 | Medium |
| Liver | 6.8 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-lymphocytes (GM12878) | 35.2 | High expression |
| Monocytes (THP-1) | 28.9 | High expression |
| HeLa | 12.5 | Medium expression |
| HEK293 | 9.8 | Medium expression |
| K562 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.224C>T (p.Thr75Met) | Missense | Rare | Loss of proteasome activity; associated with PRAAS1 |
| c.404C>T (p.Pro135Leu) | Missense | Rare | Impaired subunit assembly; causes JMP syndrome |
| c.145G>A (p.Gly49Arg) | Missense | Rare | Reduced catalytic activity; linked to CANDLE syndrome |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of protein; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most PSMB8 mutations are loss-of-function, reducing proteasome catalytic activity and leading to accumulation of ubiquitinated proteins and interferonopathy.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by incorporating into proteasome complexes and impairing overall function.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004175 ~ endopeptidase activity | • GO:0005839 ~ proteasome core complex |
| • GO:0006511 ~ ubiquitin-dependent protein catabolic process | • GO:0002474 ~ antigen processing and presentation of peptide antigen via MHC class I |
| • GO:0031593 ~ polyubiquitin modification-dependent protein binding |
Pathways
• Immunoproteasome pathway (Reactome: R-HSA-1236974)
• Antigen processing and presentation (KEGG: hsa04612)
• Proteasome degradation (KEGG: hsa03050)
Protein Summary
PSMB8 (proteasome subunit beta 8) is a 276-amino acid protein that forms part of the 20S immunoproteasome core. It possesses chymotrypsin-like catalytic activity, cleaving peptides after hydrophobic residues. The protein is induced by interferon-gamma and replaces the constitutive beta 5 subunit. Its structure includes a catalytic N-terminal threonine residue. Defects in PSMB8 lead to autoinflammatory diseases due to impaired protein degradation and chronic type I interferon signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSMB8 Knockout HEK293 Cell Line | EDJ-KQ50545 | Human | 5696 | Details Get a Quote |
| PSMB8 Knockout HeLa Cell Line | EDJ-KQ54247 | Human | 5696 | Details Get a Quote |
| PSMB8 Knockout A-549 Cell Line | EDJ-KQ62738 | Human | 5696 | Details Get a Quote |
| PSMB8 Knockout HCT 116 Cell Line | EDJ-KQ71209 | Human | 5696 | Details Get a Quote |
| PSMB8 Knockout HAP1 Cell Line | EDC09215 | Human | 5696 | Details Get a Quote |
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