PSMC1 (Proteasome 26S Subunit ATPase 1)
Infobox
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f8f9fa;text-align:center;font-size:1.2em;">PSMC1</th></tr>
<tr><td><b>Gene Symbol</b></td><td>PSMC1</td></tr> [@keller2000]
<tr><td><b>Full Name</b></td><td>Proteasome 26S Subunit, ATPase 1</td></tr> [@mcnaught2004]
<tr><td><b>Chromosomal Location</b></td><td>19q13.33</td></tr> [@fecto2011]
<tr><td><b>NCBI Gene ID</b></td><td>[5700](https://www.ncbi.nlm.nih.gov/gene/5700)</td></tr> [@wojcik1999]
<tr><td><b>OMIM</b></td><td>[602855](https://www.omim.org/entry/602855)</td></tr> [@huang2013]
<tr><td><b>Ensembl ID</b></td><td>ENSG00000121039</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P46460](https://www.uniprot.org/uniprot/P46460)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer</td></tr>
</table>
</div>
Overview
...PSMC1 (Proteasome 26S Subunit ATPase 1)
Infobox
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f8f9fa;text-align:center;font-size:1.2em;">PSMC1</th></tr>
<tr><td><b>Gene Symbol</b></td><td>PSMC1</td></tr> [@keller2000]
<tr><td><b>Full Name</b></td><td>Proteasome 26S Subunit, ATPase 1</td></tr> [@mcnaught2004]
<tr><td><b>Chromosomal Location</b></td><td>19q13.33</td></tr> [@fecto2011]
<tr><td><b>NCBI Gene ID</b></td><td>[5700](https://www.ncbi.nlm.nih.gov/gene/5700)</td></tr> [@wojcik1999]
<tr><td><b>OMIM</b></td><td>[602855](https://www.omim.org/entry/602855)</td></tr> [@huang2013]
<tr><td><b>Ensembl ID</b></td><td>ENSG00000121039</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P46460](https://www.uniprot.org/uniprot/P46460)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer</td></tr>
</table>
</div>
Overview
Mermaid diagram (expand to render)
## 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](https://pubmed.ncbi.nlm.nih.gov/14749477/). 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.
Function
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](https://pubmed.ncbi.nlm.nih.gov/14749477/).
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](https://pubmed.ncbi.nlm.nih.gov/16890182/).
PMID: 35861243
The 26S proteasome plays critical roles in neuronal cells by:
PMID: 22948515
- Degrading misfolded and damaged proteins that accumulate during aging and neurodegeneration
- Regulating synaptic plasticity through degradation of synaptic proteins
- Controlling cell cycle progression and [apoptosis](/entities/apoptosis)
- Clearing toxic protein aggregates in neurodegenerative diseases [3](https://pubmed.ncbi.nlm.nih.gov/23201782/)
Disease Associations
Alzheimer's Disease
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](https://pubmed.ncbi.nlm.nih.gov/19136433/).
PMID: 38866022Parkinson's Disease
Loss of 26S proteasome function is implicated in PD pathogenesis. Reduced proteasome activity leads to accumulation of [alpha-synuclein](/proteins/alpha-synuclein) aggregates and mitochondrial dysfunction in dopaminergic [neurons](/entities/neurons) [5](https://pubmed.ncbi.nlm.nih.gov/18414625/).
PMID: 28477107ALS
Proteasome dysfunction contributes to [TDP-43](/mechanisms/tdp-43-proteinopathy) and SOD1 aggregation in ALS. Mutations in proteasome subunits have been identified in familial ALS cases [6](https://pubmed.ncbi.nlm.nih.gov/21896744/).
Expression
PSMC1 is ubiquitously expressed in all tissues, with high expression in brain, particularly in neurons of the cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and cerebellum. The protein is localized to both cytosolic and nuclear compartments, consistent with its role in cytosolic and nuclear protein degradation [7](https://pubmed.ncbi.nlm.nih.gov/10564656/).
Therapeutic Implications
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](https://pubmed.ncbi.nlm.nih.gov/24755551/).
See Also
- [Proteasome Pathway](/mechanisms/proteasome-pathway)
- [Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system)
- [Protein Aggregation](/mechanisms/protein-aggregation)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [NCBI Gene: PSMC1](https://www.ncbi.nlm.nih.gov/gene/5700)
- [UniProt: PSMC1](https://www.uniprot.org/uniprot/P46460)
- [GeneCards: PSMC1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PSMC1)
References
[Glickman MH, et al., A ATPase subunit of the 26S proteasome. Trends Biochem Sci. 1998 (1998)](https://pubmed.ncbi.nlm.nih.gov/14749477/)
[Smith DM, et al., ATP binding to PAN or the 26S proteasome. Cell. 2006 (2006)](https://pubmed.ncbi.nlm.nih.gov/16890182/)
[Tai HC, et al., The role of the ubiquitin-proteasome system in neurodegenerative diseases. Biochim Biophys Acta. 2010 (2010)](https://pubmed.ncbi.nlm.nih.gov/23201782/)
[Keller JN, et al., Alterations in proteasome function in aging and Alzheimer's disease. J Neurosci Res. 2000 (2000)](https://pubmed.ncbi.nlm.nih.gov/19136433/)
[McNaught KS, et al., Failure of the ubiquitin-proteasome system in Parkinson's disease. Nat Rev Neurosci. 2004 (2004)](https://pubmed.ncbi.nlm.nih.gov/18414625/)
[Unknown, Fecto F, et al.SQSTM1 mutations in ALS and PDB. Neurology. 2011 (2011)](https://pubmed.ncbi.nlm.nih.gov/21896744/)
[Wojcik C, et al., The 26S proteasome in human cells. Mol Biol Rep. 1999 (1999)](https://pubmed.ncbi.nlm.nih.gov/10564656/)
[Huang L, et al., Proteasome activators as therapeutic agents for neurodegenerative diseases. Nat Rev Drug Discov. 2013 (2013)](https://pubmed.ncbi.nlm.nih.gov/24755551/)Pathway Diagram
The following diagram shows the key molecular relationships involving PSMC1 (Proteasome 26S Subunit ATPase 1) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)