enzyme

PROTEASOME

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about PROTEASOME: 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.

940Connections

4Hypotheses

0Analyses

50Outgoing

50Incoming

0Experiments

0Debates

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🔬 Protein Info

Gene Symbol	PROTEASOME
Pathways	APOPTOSIS, AUTOPHAGY, Cerebrovascular, Chaperone, FERROPTOSIS
GeneCards	PROTEASOME
Human Protein Atlas	PROTEASOME
beta5 (PSMB5)	Chymotrypsin-like activity - cleaves after hydrophobic residues
beta2 (PSMB6)	Trypsin-like activity - cleaves after basic residues
beta1 (PSMB7)	Caspase-like activity - cleaves after acidic residues
Base subcomplex	Six ATPase subunits (Rpt1-6) that unfold substrates and open the alpha-ring gate
Lid subcomplex	Nine non-ATPase subunits (Rpn1-3, Rpn5-9, Rpn11-12) that recognize ubiquitinated substrates and remove ubiquitin chains
E1	Ubiquitin-activating enzyme
E2	Ubiquitin-conjugating enzyme
E3	Ubiquitin ligase (substrate recognition)
Associated Diseases	MULTIPLE SCLEROSIS, disease
Interactions	SNCA, SQSTM1, TAU
KG Connections	11 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

Proteasome Dysfunction in Progressive Supranuclear Palsy

mechanism · 1874 words

→

Pathway Diagram

graph TD
    PROTEASOME["PROTEASOME"] -->|"modulates"| HDAC6["HDAC6"]
    style HDAC6 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"activates"| UBIQUITIN["UBIQUITIN"]
    style UBIQUITIN fill:#1a2a3a,stroke:#ce93d8,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"associated"| AUTOPHAGY["AUTOPHAGY"]
    style AUTOPHAGY fill:#1a2a3a,stroke:#ffd54f,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"activates"| NEURON["NEURON"]
    style NEURON fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"interacts"| P62["P62"]
    style P62 fill:#1a2a3a,stroke:#ce93d8,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"regulates"| BECN1["BECN1"]
    style BECN1 fill:#1a2a3a,stroke:#ce93d8,stroke-width:1px,color:#e0e0e0
    PROTEASOME["PROTEASOME"] -->|"activates"| LYSOSOME["LYSOSOME"]
    style LYSOSOME fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    TAU["TAU"] -->|"interacts"| PROTEASOME["PROTEASOME"]
    style TAU fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    SNCA["SNCA"] -->|"interacts"| PROTEASOME["PROTEASOME"]
    style SNCA fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    SQSTM1["SQSTM1"] -->|"interacts"| PROTEASOME["PROTEASOME"]
    style SQSTM1 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    NRF2["NRF2"] -->|"regulates"| PROTEASOME["PROTEASOME"]
    style NRF2 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    AUTOPHAGY_1["AUTOPHAGY"] -->|"associated"| PROTEASOME["PROTEASOME"]
    style AUTOPHAGY_1 fill:#1a2a3a,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style PROTEASOME fill:#006494,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0,font-weight:bold

Outgoing (86)

Target	Relation	Type	Str
TNF	regulates	protein	0.90
TAU	degrades	protein	0.85
TTP	modifies	protein	0.80
TNF-α mRNA stability	regulates	phenotype	0.80
Alzheimer	inhibits	disease	0.60
Cancer	therapeutic_target	disease	0.60
Ferroptosis	causes	disease	0.60
Neurodegeneration	causes	disease	0.60
Aging	inhibits	disease	0.60
Huntington	transports	disease	0.60
Parkinson	transports	disease	0.60
Alzheimer	transports	disease	0.60
Parkinson	associated_with	disease	0.60
Neurodegeneration	associated_with	disease	0.60
Prion Disease	regulates	disease	0.60
Parkinson	regulates	disease	0.60
Aging	interacts_with	disease	0.60
Amyotrophic Lateral Sclerosis	degrades	disease	0.60
Parkinson	degrades	disease	0.60
Neurodegeneration	degrades	disease	0.60
Alzheimer	degrades	disease	0.60
Neurodegeneration	therapeutic_target	disease	0.60
Als	expressed_in	disease	0.60
Alzheimer	contributes_to	disease	0.60
Als	activates	disease	0.60
Ferroptosis	degrades	disease	0.60
Dementia	activates	disease	0.60
Parkinson	activates	disease	0.60
Aging	expressed_in	disease	0.60
Cancer	expressed_in	disease	0.60
Aging	degrades	disease	0.60
Fibrosis	therapeutic_target	disease	0.60
Als	interacts_with	disease	0.60
Als	contributes_to	disease	0.60
Aging	activates	disease	0.60
Cancer	activates	disease	0.60
Alzheimer	regulates	disease	0.60
Als	therapeutic_target	disease	0.60
Parkinson	therapeutic_target	disease	0.60
Ischemia	associated_with	disease	0.60
Diabetes	regulates	disease	0.60
Als	inhibits	disease	0.60
Atherosclerosis	regulates	disease	0.60
Ischemia	inhibits	disease	0.60
Stroke	activates	disease	0.60
Blood-Brain Barrier	activates	pathway	0.55
Mapk	therapeutic_target	pathway	0.55
Nf-Κb	therapeutic_target	pathway	0.55
Wnt	therapeutic_target	pathway	0.55
Pi3K/Akt	therapeutic_target	pathway	0.55

Incoming (854)

Source	Relation	Type	Str
UBIQUITIN	inhibits	gene	1.00
NEURODEGENERATION	therapeutic_target	gene	1.00
PARKINSON	therapeutic_target	gene	1.00
AUTOPHAGY	activates	gene	1.00
CANCER	therapeutic_target	gene	1.00
PARKINSON'S DISEASE	therapeutic_target	gene	1.00
AUTOPHAGY	regulates	gene	1.00
UBIQUITIN	regulates	gene	1.00
Als	therapeutic_target	disease	1.00
UBIQUITIN	therapeutic_target	gene	1.00
Als	inhibits	disease	1.00
Neurodegeneration	therapeutic_target	disease	1.00
UBIQUITIN	activates	gene	1.00
Als	activates	disease	1.00
Als	regulates	disease	1.00
Parkinson	therapeutic_target	disease	1.00
AUTOPHAGY	associated_with	gene	1.00
Neurodegeneration	activates	disease	1.00
NEURODEGENERATION	associated_with	gene	1.00
UBIQUITIN	associated_with	gene	1.00
NEURODEGENERATION	activates	gene	1.00
Cancer	therapeutic_target	disease	1.00
Tumor	therapeutic_target	disease	1.00
GENES	activates	gene	1.00
AUTOPHAGY	therapeutic_target	gene	1.00
P53	therapeutic_target	gene	1.00
P62	activates	gene	1.00
Aging	therapeutic_target	disease	1.00
LYSOSOME	activates	gene	1.00
Neurodegeneration	associated_with	disease	1.00
UCH37	associated_with	enzyme	0.95
Als	associated_with	disease	0.95
UBIQUITIN	binds_to	protein	0.90
CANCER	inhibits	gene	0.90
NEURODEGENERATION	regulates	gene	0.90
SQSTM1	activates	gene	0.90
Aging	activates	disease	0.90
APOPTOSIS	therapeutic_target	gene	0.90
Neurodegeneration	causes	disease	0.90
NEURODEGENERATION	causes	gene	0.90
NEURON	expressed_in	cell_type	0.85
SQSTM1	associated_with	entity	0.85
TAU	associated_with	entity	0.85
Cancer	regulates	disease	0.85
SNCA	interacts_with	protein	0.85
TAU	interacts_with	protein	0.85
SQSTM1	interacts_with	protein	0.85
NRF2	regulates	entity	0.80
AUTOPHAGY	associated_with	entity	0.80
NEURODEGENERATION	inhibits	gene	0.80

Targeting Hypotheses (4)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
VCP/p97 ATPase mutations impair extraction of ubiquitinated	0.720	neurodegeneration	What are the neuron-specific effects of
Early Proteasome Restoration Therapy	0.712	neurodegeneration	Gene expression changes in aging mouse b
Chaperone-Degradation Coupling Prevents Aggregate Persistenc	0.632	protein folding	Can chaperone enhancement approaches ove
proteasome shuttle failure defines the therapeutic window fo	0.327	neurodegeneration	How do ALS-linked UBQLN2 mutations affec

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (0)

Experimental studies targeting or related to this entity

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

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
The genetics of amyotrophic lateral sclerosis. [PMID:38967083]	Nijs M, Van Damme P	Curr Opin Neurol	2024	1
Unveiling the Genomic Landscape of Yan Goose (Anser cygnoides): Insights into Po [PMID:41594384]	Qi S, Ai Z, Cai Y, Zhang Y, Zhao W et al	Animals (Basel)	2026	0
NAD+ restores proteostasis through splicing-dependent autophagy. [PMID:41313318]	Ai R, Fang EF	Autophagy	2026	0
CHIP and aging: a key regulator of proteostasis and cellular senescence. [PMID:40323531]	Pandey Surya Nath; Agrawal Neetu; Moglad	Biogerontology	2025	0
Carnitine Shuttle and Ferroptosis in Cancer. [PMID:40867868]	Kim YA, Lee Y, Kim MS	Antioxidants (Basel)	2025	0
Proteostasis and autophagy disruption by the aging-related VGVAPG hexapeptide - [PMID:40348194]	Unknown	Neurochemistry international	2025	0
The genetics of amyotrophic lateral sclerosis. [PMID:38967083]	Nijs M, Van Damme P	Curr Opin Neurol	2024	0
Endogenous retroviruses are dysregulated in ALS. [PMID:38989463]	Pasternack, Doucet-O'Hare, Johnson, Paul	iScience	2024	0
Endogenous retroviruses are dysregulated in ALS. [PMID:38989463]	Unknown	iScience	2024	0
A Potential Mechanism for Targeting Aggregates With Proteasomes and Disaggregase [PMID:35517053]	Unknown	Frontiers in aging neuroscienc	2022	0
Deciphering the Link Between ER<sup>UPR</sup> Signaling and MicroRNA in Pathogen [PMID:35615589]	Unknown	Frontiers in aging neuroscienc	2022	0
REM Sleep: An Unknown Indicator of Sleep Quality. [PMID:34948586]	Barbato G	Int J Environ Res Public Healt	2021	0
How autophagy can restore proteostasis defects in multiple diseases? [PMID:32043639]	Unknown	Medicinal research reviews	2021	0
LRSAM1 E3 ubiquitin ligase promotes proteasomal clearance of E6-AP protein. [PMID:33207262]	Unknown	Cellular signalling	2021	0
Amyloid toxicity in a Drosophila Alzheimer's model is ameliorated by autophagy a [PMID:34062489]	Unknown	Neurobiology of aging	2021	0
Diagnostic and therapeutic options in recurrent implantation failure. [PMID:32266059]	Moustafa S, Young SL	F1000Res	2020	0
Organ Failure Due to Systemic Injury in Acute Pancreatitis. [PMID:30768987]	Garg PK, Singh VP	Gastroenterology	2019	0
Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiologic [PMID:31185581]	van den Bos, Geevasinga, Higashihara, Me	International journal of molec	2019	0
ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now? [PMID:31866818]	Mejzini R, Flynn LL, Pitout IL	Front Neurosci	2019	0
Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiologic [PMID:31185581]	Unknown	International journal of molec	2019	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning PROTEASOME in their description or question text

No additional research found