gene

USP14

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

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.

48Connections

1Hypotheses

1Analyses

37Outgoing

11Incoming

0Experiments

1Debates

Summary

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.

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🧬 Gene Info

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	ATXN3, AUTOPHAGY, BRCC3, CANCER, CYLD, PINK1
KG Connections	48 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

USP14 Gene

gene · 1145 words

→

USP14 Protein

protein · 657 words

→

Pathway Diagram

graph TD
    USP14["USP14"]
    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

Outgoing (37)

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
Atherosclerosis	associated_with	disease	0.65
Cardiovascular	associated_with	disease	0.65
Tumor	inhibits	disease	0.65
Cancer	inhibits	disease	0.65
oxidative stress response	participates_in	pathway	0.60
neurons	expressed_in	cell_type	0.60
autophagy pathway	participates_in	pathway	0.60
ALDH2	associated_with	gene	0.60
CGAS	associated_with	gene	0.60
CANCER	inhibits	gene	0.60
Autophagy	therapeutic_target	pathway	0.60
Immunotherapy	activates	pathway	0.60
ubiquitin-proteasome	participates_in	pathway	0.60
Autophagy	inhibits	pathway	0.60
USP5	implicated_in	gene	0.60
Er Stress	inhibits	pathway	0.60
stem cells	expressed_in	cell_type	0.60
SQSTM1	associated_with	gene	0.60
P62	associated_with	gene	0.60
CD8	therapeutic_target	gene	0.60
UBIQUITIN	activates	gene	0.60
blood-brain barrier	participates_in	pathway	0.60
USP9X	implicated_in	gene	0.60
USP25	interacts_with	gene	0.60
Macrophage	expressed_in	cell_type	0.55
19S_proteasome	associated_with	mechanism	0.50
proteasome_substrates	removes_ubiquitin_from	mechanism	0.50

Incoming (11)

Source	Relation	Type	Str
genes-usp14	documents	wiki	1.00
genes-usp14	describes	wiki	1.00
USF1	activates	gene	0.90
USP13	interacts_with	gene	0.60
AUTOPHAGY	therapeutic_target	gene	0.60
BRCC3	interacts_with	gene	0.60
AUTOPHAGY	inhibits	gene	0.60
CYLD	interacts_with	gene	0.60
ATXN3	interacts_with	gene	0.60
UCHL1	interacts_with	gene	0.60
PINK1	inhibits	gene	0.60

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
USP14 Inhibition to Accelerate Proteasomal Degradation of Sy	0.486	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (1)

Scientific analyses that reference this entity

Quantitative proteomics of the aging synapse: protein turnover and aggregation i

proteomics | 2026-04-16 | 16 hypotheses Top: 0.591

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (1)

Multi-agent debates referencing this entity

How does synaptic protein turnover change with age and neurodegeneration, and wh

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Related Research

Hypotheses and analyses mentioning USP14 in their description or question text

No additional research found