| PSMC1 | |
|---|---|
| Gene Symbol | PSMC1 |
| Full Name | Proteasome 26S Subunit, ATPase 1 |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | [5700](https://www.ncbi.nlm.nih.gov/gene/5700) |
| OMIM | [602855](https://www.omim.org/entry/602855) |
| Ensembl ID | ENSG00000121039 |
| UniProt ID | [P46460](https://www.uniprot.org/uniprot/P46460) |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, ALS, Cancer |
## is a human gene whose product pSMC1 (Proteasome 26S Subunit, ATPase 1)** encodes a member of the ATPase family that functions as a regulatory subunit of the 26S proteasome. The 26S proteasome is a large, multi-subunit protease complex responsible for targeted degradation of ubiquitinated proteins, playing essential roles in cellular protein quality control, cell cycle regulation, and stress response 1. Variants in ## have been implicated in Alzheimer's Disease, Parkinson's Disease, ALS. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
PSMC1 (Proteasome 26S Subunit, ATPase 1) encodes a member of the ATPase family that functions as a regulatory subunit of the 26S proteasome. The 26S proteasome is a large, multi-subunit protease complex responsible for targeted degradation of ubiquitinated proteins, playing essential roles in cellular protein quality control, cell cycle regulation, and stress response 1.
PSMC1 is a component of the 19S regulatory particle (also called the PA700 complex) that recognizes, unfolds, and translocates ubiquitinated substrates into the 20S catalytic core particle for degradation. The ATPase subunits (PSMC1-6) provide the mechanical energy for substrate unfolding and gate opening 2.
The 26S proteasome plays critical roles in neuronal cells by:
The proteasome system is impaired in AD brains, with reduced 26S proteasome activity contributing to accumulation of ubiquitinated protein aggregates. PSMC1 expression is altered in AD, reflecting disrupted proteostasis 4.
Loss of 26S proteasome function is implicated in PD pathogenesis. Reduced proteasome activity leads to accumulation of alpha-synuclein aggregates and mitochondrial dysfunction in dopaminergic neurons 5.
Proteasome dysfunction contributes to TDP-43 and SOD1 aggregation in ALS. Mutations in proteasome subunits have been identified in familial ALS cases 6.
PSMC1 is ubiquitously expressed in all tissues, with high expression in brain, particularly in neurons of the cerebral cortex, hippocampus, and cerebellum. The protein is localized to both cytosolic and nuclear compartments, consistent with its role in cytosolic and nuclear protein degradation 7.
Proteasome activators are being investigated as therapeutic agents for neurodegenerative diseases. The FDA-approved proteasome inhibitor bortezomib is used in cancer treatment, while proteasome activators represent an opposite approach for neurodegeneration 8.