PSMC2: Proteasome 26S Subunit ATPase 2
A core component of the 19S regulatory particle of the 26S proteasome, essential for ubiquitin-dependent protein degradation.
Gene Information Card
| Symbol | PSMC2 |
|---|---|
| Full Name | Proteasome 26S Subunit, ATPase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 5701 ncbi.nlm.nih.gov/gene/5701 |
| Ensembl ID | ENSG00000106537 |
| UniProt ID | P35998 |
| OMIM ID | 602708 |
| HGNC ID | 9550 |
| Aliases | S7, MSS1, p97 |
Description
PSMC2 (Proteasome 26S Subunit, ATPase 2) encodes a member of the AAA ATPase family that forms part of the 19S regulatory particle of the 26S proteasome. This ATPase subunit is essential for substrate unfolding and translocation into the 20S core particle, playing a critical role in ubiquitin-dependent proteolysis. The protein is involved in cell cycle regulation, apoptosis, and DNA damage repair.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Proteasome-associated autoinflammatory syndrome (PRAAS) | Loss-of-function mutations impair proteasome assembly and activity, leading to chronic inflammation and immune dysregulation. | ClinVar, OMIM |
| Hepatocellular carcinoma | Overexpression of PSMC2 promotes tumor growth by enhancing degradation of tumor suppressors. | COSMIC, PubMed |
| Breast cancer | Upregulation correlates with poor prognosis; PSMC2 silencing reduces proliferation. | COSMIC, PubMed |
| Neurodegenerative disorders (e.g., Alzheimer's disease) | Dysregulated proteasomal activity leads to accumulation of misfolded proteins. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.2 | High |
| Bone marrow | 30.5 | High |
| Lymph node | 28.1 | High |
| Brain | 15.4 | Medium |
| Liver | 12.8 | Medium |
| Heart | 10.3 | Medium |
| Skeletal muscle | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 42.5 | Cervical carcinoma; high expression |
| K562 | 38.9 | Leukemia; high expression |
| HEK293 | 35.2 | Embryonic kidney; high expression |
| HepG2 | 30.1 | Hepatocellular carcinoma; high expression |
| SH-SY5Y | 18.4 | Neuroblastoma; moderate 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% | Loss of start codon; likely loss of function |
| c.632C>T (p.Thr211Met) | Missense | <0.01% | Impaired ATPase activity; associated with PRAAS |
| c.1078G>A (p.Glu360Lys) | Missense | <0.01% | Reduced proteasome assembly; pathogenic |
| c.1249C>T (p.Arg417Cys) | Missense | <0.01% | Unknown significance; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt ATPase activity or proteasome assembly (e.g., p.Thr211Met) lead to impaired protein degradation and cellular stress.
Gain of Function (GOF)
Not well characterized; overexpression in cancers suggests potential oncogenic gain-of-function via enhanced degradation of tumor suppressors.
Dominant Negative (DN)
Heterozygous missense mutations in the ATPase domain can interfere with wild-type subunit function, reducing overall proteasome activity.
View complete mutation data：
Gene Ontology (GO)
| • ATP hydrolysis activity | • proteasome regulatory particle binding |
| • ubiquitin-dependent protein catabolic process | • protein unfolding |
| • proteasome-mediated ubiquitin-dependent protein catabolic process | • nucleotide binding |
Pathways
• Proteasome (KEGG hsa03050)
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• Cell cycle (KEGG hsa04110)
• p53 signaling pathway (KEGG hsa04115)
Protein Summary
PSMC2 (also known as S7 or MSS1) is a 433-amino-acid ATPase that forms a hexameric ring within the 19S regulatory particle of the 26S proteasome. It uses energy from ATP hydrolysis to unfold and translocate polyubiquitinated substrates into the 20S core for degradation. The protein is highly conserved and ubiquitously expressed, with highest levels in testis and bone marrow. Dysregulation of PSMC2 is implicated in cancer, autoinflammatory syndromes, and neurodegeneration.
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