| Gene Symbol | USP14 |
| Protein Type | Enzyme |
| Function | USP14 encodes a 494 amino acid cysteine protease belonging to the ubiquitin-specific protease (USP) family. |
| Amino Acids | 494 aa |
| Pathways | Er Stress, Autophagy, Immunotherapy |
| Ensembl ID | ENSG00000101557 |
| GeneCards | USP14 |
| Human Protein Atlas | USP14 |
| Chain trimming | Removing ubiquitin chains from the distal end (en bloc or sequentially), giving substrates an opportunity to escape degradation |
| Gate opening | USP14 activity allosterically promotes opening of the 20S proteasome gate, enhancing substrate entry |
| Ubiquitin recycling | Releasing intact ubiquitin chains that are then recycled back to the free ubiquitin pool |
| Substrate selection | By competing with RPN11 (which cleaves ubiquitin chains en bloc at the base), USP14 acts as a kinetic checkpoint that slows degradation of some substrates |
| [Tau](/proteins/tau) clearance | The USP14 inhibitor IU1 accelerates proteasomal degradation of tau in neuronal cultures, reducing both total and phosphorylated tau levels |
| Proteasome impairment | AD brains show reduced proteasome activity due to tau and amyloid-beta accumulation within proteasomes. USP14 inhibition overcomes this blockade by enhancing substrate processing |
| IU1 derivatives | IU1-47, a more potent analog of IU1, reduces tau levels in primary neurons and iPSC-derived human neurons at nanomolar concentrations |
| Associated Diseases | Als, Atherosclerosis, Cardiovascular, Neurodegenerative Diseases, Parkinson's Disease |
| Interactions | UBIQUITIN, USP25, CANCER, USF1, BRCC3, CYLD |
| KG Connections | 44 knowledge graph edges |
| Databases | GeneCardsUniProtNCBI GeneHPASTRING |
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