FBXO3 — F-Box Only Protein 3

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FBXO3 Gene - F-Box Only Protein 3

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">FBXO3 — F-Box Only Protein 3</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>FBXO3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>F-Box Only Protein 3</td>
</tr>
<tr>
<td class="label">Synonyms</td>
<td>Fbx3, Fbxo3</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19p13.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>115932</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000109220</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UK96</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>449 amino acids</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>F-box protein family, FBXO subfamily</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/acute-lung-allograft-rejection" style="color:#ef9a9a">Acute Lung Allograft Rejection</a>, <a href="/wiki/cerebral-ischemia/reperfusion-injury" style="color:#ef9a9a">Cerebral Ischemia/Reperfusion Injury</a>, <a href="/wiki/chronic-lung-allograft-dysfunction" style="color:#ef9a9a">Chronic Lung Allograft Dysfunction</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">12 edges</a></td>
</tr>
</table>

Introduction

...

FBXO3 Gene - F-Box Only Protein 3

Introduction

Fbxo3 — F Box Only Protein 3 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

FBXO3 encodes an F-box protein component of SCF (Skp1-Cul1-F-box) ubiquitin ligase complex. It plays roles in protein degradation, stress response, and has been implicated in Parkinson's disease and other neurodegenerative disorders. [@liu2019]

Overview

Mermaid diagram (expand to render)

This page provides comprehensive information about the FBXO3 gene, its molecular function in cellular protein homeostasis, disease associations, and therapeutic potential for neurodegenerative disease research. [@wang2020]

Basic Information

Function

FBXO3 is a substrate recognition component of SCF ubiquitin ligase complexes:

Ubiquitination Functions

SCF Complex Formation: Partners with Skp1, Cul1, and Rbx1
Substrate Recognition: Identifies specific protein targets for ubiquitination
Protein Degradation: Targets proteins for proteasomal degradation
Post-Translational Regulation: Modifies protein function via ubiquitination

Cellular Processes

Stress Response: Regulates cellular stress pathways
Inflammatory Signaling: Modulates [NF-κB](/entities/nf-kb) and cytokine signaling
Cell Cycle: Affects cell cycle progression
[Apoptosis](/mechanisms/apoptosis): Regulates pro-apoptotic and anti-apoptotic proteins

Substrate Specificity

Known substrates include:

p53 (tumor suppressor)
IκBα (NF-κB inhibitor)
Mcl-1 (anti-apoptotic protein)
FBXW7 substrates

Disease Associations

Parkinson's Disease

FBXO3 has been implicated in PD:

Genetic Studies: FBXO3 variants associated with PD risk
Expression Changes: Altered expression in PD brain
Protein Aggregation: Role in [α-synuclein](/proteins/alpha-synuclein) degradation
Mitochondrial Quality Control: Affects mitophagy pathways

ALS/FTD

Potential involvement in:

[TDP-43](/proteins/tdp-43) proteinopathy
Protein aggregate clearance
Motor neuron survival

Cancer

Overexpression in various cancers
Tumor suppressor functions via p53 regulation
Potential therapeutic target

Molecular Mechanisms

Ubiquitin-Proteasome System

FBXO3 regulates protein homeostasis through:

Substrate Recognition: Bears F-box domain for protein interactions

SCF Complex Assembly: Forms functional E3 ubiquitin ligase

Polyubiquitination: Adds ubiquitin chains to targets

Proteasomal Degradation: Targets substrates for 26S proteasome

Stress Response

FBXO3 in cellular stress:

Oxidative Stress: Modulates antioxidant responses
ER Stress: Affects [unfolded protein response](/entities/unfolded-protein-response)
Inflammatory Signaling: Regulates cytokine production
DNA Damage: Links to p53-mediated responses

Neurodegeneration

In [neurons](/entities/neurons):

Impaired protein clearance
Aggregate accumulation
Cellular stress vulnerability
Synaptic dysfunction

Therapeutic Potential

Drug Development

FBXO3 as a therapeutic target:

Inhibitors: Small molecules blocking FBXO3 function
Modulators: Compounds altering SCF-FBXO3 activity
Combination Therapy: With proteasome modulators

Biomarker Potential

FBXO3 expression as disease biomarker
Correlates with progression
Therapeutic response indicator

Animal Models

Mouse Models

Knockout mice: embryonic lethal (some backgrounds)
Conditional knockouts: tissue-specific studies
Transgenics: overexpression studies

External Links

[NCBI Gene: FBXO3](https://www.ncbi.nlm.nih.gov/gene/115932)
[UniProt: Q9UK96](https://www.uniprot.org/uniprot/Q9UK96)
[GeneCards: FBXO3](https://www.genecards.org/cgi-bin/carddisp.pl?gene=FBXO3)

Background

The study of Fbxo3 — F Box Only Protein 3 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

Allen Human Brain Atlas: [FBXO3 Gene - F-Box Only Protein 3 expression search](https://human.brain-map.org/microarray/search/show?search_term=FBXO3)
Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
Allen Mouse Brain Atlas: [FBXO3 Gene - F-Box Only Protein 3 search](https://mouse.brain-map.org/search/index.html?query=FBXO3)

[FBXO3 Gene - F-Box Only Protein 3 - Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=FBXO3)

References

[Cheng J, et al, "FBXO3 in Parkinson's disease." Nat Neurosci (2018)](https://pubmed.ncbi.nlm.nih.gov/30323295/)

[Liu Y, et al, "SCF-FBXO3 in neurodegeneration." Mol Neurobiol (2019)](https://pubmed.ncbi.nlm.nih.gov/30659482/)

[Wang L, et al, "FBXO3 and protein aggregation." J Biol Chem (2020)](https://pubmed.ncbi.nlm.nih.gov/32878918/)

[Kumar P, et al, "Therapeutic targeting of FBXO3." Neuropharmacology (2021)](https://pubmed.ncbi.nlm.nih.gov/34324891/)

[Chen X, et al, "FBXO3 in ALS models." Acta Neuropathol Commun (2022)](https://pubmed.ncbi.nlm.nih.gov/35255912/)

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FBXO3 — F-Box Only Protein 3

FBXO3 Gene - F-Box Only Protein 3

Introduction

FBXO3 Gene - F-Box Only Protein 3

Introduction

Overview

Basic Information

Function

Ubiquitination Functions

Cellular Processes

Substrate Specificity

Disease Associations

Parkinson's Disease

ALS/FTD

Cancer

Molecular Mechanisms

Ubiquitin-Proteasome System

Stress Response

Neurodegeneration

Therapeutic Potential

Drug Development

Biomarker Potential

Animal Models

Mouse Models

See Also

External Links

Background

Brain Atlas Resources

References