PSMA3: Proteasome 20S Subunit Alpha 3
Core component of the 20S proteasome complex involved in protein degradation and cellular homeostasis.
Gene Information Card
| Symbol | PSMA3 |
|---|---|
| Full Name | Proteasome 20S Subunit Alpha 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q23.1 |
| NCBI Gene ID | 5684 ncbi.nlm.nih.gov/gene/5684 |
| Ensembl ID | ENSG00000100567 |
| UniProt ID | P25788 |
| OMIM ID | 176843 |
| HGNC ID | 9533 |
| Aliases | HC8, PSC3, proteasome subunit alpha type-3 |
Description
PSMA3 encodes the alpha 3 subunit of the 20S core proteasome complex. This subunit is essential for proteasome assembly and proteolytic activity, mediating the degradation of ubiquitinated proteins. It plays a critical role in cell cycle regulation, apoptosis, and antigen processing.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Proteasome-associated autoinflammatory syndrome (PRAAS) | Loss-of-function mutations impair proteasome activity, leading to accumulation of ubiquitinated proteins and chronic inflammation. | PMID: 26073778 |
| Multiple myeloma | Overexpression of PSMA3 contributes to resistance to proteasome inhibitors (e.g., bortezomib). | PMID: 23341540 |
| Colorectal cancer | Upregulation of PSMA3 correlates with poor prognosis and increased tumor proliferation. | PMID: 29187742 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.5 | Medium |
| Heart | 22.3 | Medium |
| Liver | 35.1 | High |
| Kidney | 28.7 | High |
| Testis | 40.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 45.0 | High expression |
| HeLa | 38.2 | High expression |
| K562 | 30.5 | Medium expression |
| MCF7 | 25.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.404C>T (p.Thr135Met) | Missense | Rare | Reduced proteasome activity; associated with PRAAS |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; likely pathogenic |
| c.637G>A (p.Gly213Arg) | Missense | Rare | Impaired subunit assembly; reported in autoinflammatory disease |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce proteasome catalytic activity, leading to protein aggregation and immune dysregulation.
Gain of Function (GOF)
Not well documented; overexpression in cancers may confer resistance to apoptosis.
Dominant Negative (DN)
Some missense mutations (e.g., p.Thr135Met) may interfere with wild-type subunit incorporation, reducing overall proteasome function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa03050 - Proteasome
• hsa04120 - Ubiquitin mediated proteolysis
• hsa05016 - Huntington disease
• hsa05202 - Transcriptional misregulation in cancer
Protein Summary
PSMA3 is a 255-amino acid protein that forms part of the alpha ring of the 20S proteasome. It is involved in substrate recognition and gate opening. The protein is highly conserved and ubiquitously expressed. Structural integrity of PSMA3 is critical for proteasome function; mutations can lead to autoinflammatory syndromes or contribute to cancer progression.
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