Entity Detail — Knowledge Graph Node
This page aggregates everything SciDEX knows about USP14: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.
USP14 is a gene implicated in neurodegeneration research. Key relationships include: inhibits, therapeutic target, associated with. Associated with Als, Cancer, Tumor. Connected to 15 entities in the SciDEX knowledge graph.
| 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 |
Knowledge base pages for this entity
graph TD
USP14["<b>USP14</b>"]
Als{"Als"}
USP14 -->|"associated with"| Als
Er_Stress(["Er Stress"])
USP14 -->|"inhibits"| Er_Stress
Autophagy(["Autophagy"])
USP14 -->|"inhibits"| Autophagy
neurodegeneration["neurodegeneration"]
USP14 -->|"implicated in"| neurodegeneration
AUTOPHAGY["AUTOPHAGY"]
AUTOPHAGY -->|"inhibits"| USP14
style USP14 fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0| Target | Relation | Type | Str |
|---|---|---|---|
| NLRC5 | promotes | protein | 0.90 |
| Neurodegenerative Diseases | associated_with | disease | 0.85 |
| PINK1 | independent_of | gene | 0.80 |
| Parkin | independent_of | gene | 0.80 |
| MITOL | requires | gene | 0.80 |
| MARCH5 | requires | gene | 0.80 |
| Parkinson's Disease | implicated_in | disease | 0.80 |
| Als | associated_with | disease | 0.75 |
| ubiquitin-proteasome system | regulates | pathway | 0.70 |
| autophagy-lysosomal pathway | regulates | pathway | 0.70 |
| Tumor | inhibits | disease | 0.65 |
| Cancer | inhibits | disease | 0.65 |
| Cardiovascular | associated_with | disease | 0.65 |
| Atherosclerosis | associated_with | disease | 0.65 |
| SQSTM1 | associated_with | gene | 0.60 |
| P62 | associated_with | gene | 0.60 |
| CD8 | therapeutic_target | gene | 0.60 |
| UBIQUITIN | activates | gene | 0.60 |
| ALDH2 | associated_with | gene | 0.60 |
| CGAS | associated_with | gene | 0.60 |
| USP25 | interacts_with | gene | 0.60 |
| USP9X | implicated_in | gene | 0.60 |
| Er Stress | inhibits | pathway | 0.60 |
| Autophagy | inhibits | pathway | 0.60 |
| CANCER | inhibits | gene | 0.60 |
| Autophagy | therapeutic_target | pathway | 0.60 |
| Immunotherapy | activates | pathway | 0.60 |
| blood-brain barrier | participates_in | pathway | 0.60 |
| stem cells | expressed_in | cell_type | 0.60 |
| USP5 | implicated_in | gene | 0.60 |
| ubiquitin-proteasome | participates_in | pathway | 0.60 |
| oxidative stress response | participates_in | pathway | 0.60 |
| autophagy pathway | participates_in | pathway | 0.60 |
| neurons | expressed_in | cell_type | 0.60 |
| Macrophage | expressed_in | cell_type | 0.55 |
Hypotheses where this entity is a therapeutic target
| Hypothesis | Score | Disease | Analysis |
|---|---|---|---|
| No targeting hypotheses | |||
Scientific analyses that reference this entity
No analyses mention this entity
Scientific publications cited in analyses involving this entity
| Title & PMID | Authors | Journal | Year | Citations |
|---|---|---|---|---|
| No papers found | ||||