FBXO3 — F-Box Only Protein 3

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

<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 — 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

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

See Also

• [Parkinson's Disease](/diseases/parkinsons-disease) - PD overview
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis) - ALS overview
• [Protein Quality Control](/mechanisms/protein-quality-control-network) - [UPS](/mechanisms/ubiquitin-proteasome-system) overview
• [Ubiquitin-Proteasome System](/mechanisms/ubiquitin-proteasome-system) - Protein degradation

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/)