PSMD2: Proteasome 26S Subunit, Non-ATPase 2
A core component of the 26S proteasome regulatory particle involved in ubiquitin-dependent protein degradation.
Gene Information Card
| Symbol | PSMD2 |
|---|---|
| Full Name | Proteasome 26S Subunit, Non-ATPase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.1 |
| NCBI Gene ID | 5708 ncbi.nlm.nih.gov/gene/5708 |
| Ensembl ID | ENSG00000175197 |
| UniProt ID | Q13200 |
| OMIM ID | 603481 |
| HGNC ID | 9560 |
| Aliases | RPN1, S2, p97 |
Description
PSMD2 (Proteasome 26S Subunit, Non-ATPase 2) encodes a component of the 19S regulatory particle (RP) of the 26S proteasome. This subunit, also known as RPN1, is essential for substrate recognition, deubiquitination, and translocation into the 20S core particle. It plays a critical role in the ubiquitin-proteasome pathway, regulating protein turnover and cellular homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Proteasome-associated autoinflammatory syndromes (PRAAS) | PSMD2 mutations may impair proteasome assembly or function, leading to interferonopathy and inflammation. | ClinVar, OMIM |
| Neurodegenerative disorders (e.g., Alzheimer's disease) | Dysregulation of proteasomal degradation of tau and beta-amyloid; PSMD2 expression changes observed. | NCBI Gene, PubMed |
| Cancer (multiple types) | Altered PSMD2 expression affects degradation of oncoproteins and tumor suppressors; implicated in breast, lung, and colorectal cancers. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 24.5 | High |
| Liver | 22.1 | High |
| Kidney | 20.8 | High |
| Heart | 18.3 | Medium |
| Lung | 16.7 | Medium |
| Skeletal Muscle | 14.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 28.1 | High expression |
| HeLa | 26.3 | High expression |
| K562 | 22.7 | High expression |
| HepG2 | 20.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Likely loss of start codon; predicted loss of function |
| c.1072C>T (p.Arg358Trp) | Missense | <0.01% | Unknown significance; reported in ClinVar |
| c.1430_1431insA (p.Asn477Lysfs*2) | Frameshift | <0.01% | Loss of function; associated with PRAAS |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or prevent proper assembly of the 19S regulatory particle.
Gain of Function (GOF)
Not well documented; no known gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations that disrupt proteasome assembly may exert dominant-negative effects by incorporating mutant subunits into the complex.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Proteasome degradation (KEGG: hsa03050)
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Parkinson's disease (KEGG: hsa05012)
Protein Summary
PSMD2 (RPN1) is a 97 kDa non-ATPase subunit of the 19S regulatory particle. It contains multiple proteasome-cyclin (PC) repeats and a C-terminal domain that mediates interactions with other RP subunits and ubiquitin receptors. The protein is essential for proteasome assembly and function, facilitating the recognition and deubiquitination of substrates before degradation.
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