| F-box Protein 31 | |
|---|---|
| Protein Name | F-box Protein 31 |
| Gene | [FBXO31](/genes/fbxo31) |
| UniProt ID | [Q8IFY6](https://www.uniprot.org/uniprot/Q8IFY6) |
| Molecular Weight | ~56 kDa |
| Subcellular Localization | Nucleus, Cytoplasm |
| Protein Family | F-box family (SCF ubiquitin ligase) |
| Aliases | FBX31, MBTPS1 |
| Brain Expression | Cerebellum, [hippocampus](/brain-regions/hippocampus), cerebral [cortex](/brain-regions/cortex) |
F-box Protein 31 (FBXO31) is a substrate recognition component of the SCF (Skp1-Cul1-F-box) ubiquitin ligase complex [1]. Unlike many F-box proteins that target proteins for degradation, FBXO31 has emerged as a unique neuroprotective protein that is upregulated in response to cellular stress. This page describes its structure, normal function in the nervous system, role in neurodegenerative diseases, and therapeutic potential.
FBXO31 possesses the characteristic F-box protein architecture:
The F-box domain enables FBXO31 to assemble into the SCF^FBXO31 ubiquitin ligase complex, which then targets specific substrates for ubiquitination [2].
FBXO31 plays critical roles in cell cycle control:
In neurons, FBXO31 provides neuroprotection through:
FBXO31 is also expressed in glial cells:
FBXO31 has emerged as an important protective factor in Alzheimer's disease:
Amyloid-β Response: FBXO31 expression is upregulated in response to amyloid-β toxicity:
Tau Pathology: FBXO31 may affect tau phosphorylation and aggregation:
Synaptic Protection: FBXO31 helps maintain synaptic homeostasis:
In Parkinson's disease, FBXO31 shows neuroprotective effects:
α-Synuclein Clearance: FBXO31 may contribute to clearance of α-synuclein aggregates:
Mitochondrial Quality Control: FBXO31 supports dopaminergic neuron survival:
Oxidative Stress Response: Critical for neuronal resistance to oxidative damage:
Biallelic mutations in FBXO31 cause a novel form of autosomal recessive spinocerebellar ataxia (SCA):
Amyotrophic Lateral Sclerosis (ALS):
Huntington's Disease:
FBXO31 interacts with several key proteins:
| Protein | Interaction Type | Functional Consequence |
|---|---|---|
| SKP1 | Complex assembly | SCF ubiquitin ligase formation |
| CUL1 | Complex assembly | Scaffold for ubiquitination |
| Cyclin D1 | Ubiquitination | Cell cycle regulation |
| p27 | Ubiquitination | Cell cycle control |
| MIZ1 | Transcription regulation | Gene expression |
| SQSTM1/p62 | Autophagy receptor | Selective autophagy |
| OPTN | Autophagy receptor | Mitophagy |
| LC3 | Autophagosome | Autophagy initiation |
While FBXO31 is not traditionally druggable, several approaches are being explored:
FBXO31 levels in cerebrospinal fluid or blood may serve as:
Fbxo31 Knockout Mice:
Transgenic Overexpression:
FBXO31 is a neuroprotective F-box protein that plays important roles in maintaining neuronal health. Its upregulation in response to cellular stress represents an endogenous neuroprotective mechanism. In Alzheimer's and Parkinson's disease, FBXO31 helps protect neurons from toxic insults, while loss-of-function mutations cause spinocerebellar ataxia. Understanding and enhancing FBXO31 function may offer therapeutic benefits for neurodegenerative diseases.
FBXO31: a tumor suppressor F-box protein regulating cell cycle (Kumamoto et al. 2012). 2012. ↩︎
The FBXO31 ubiquitin ligase: a new player in neurodegeneration (Ciaffi et al. 2021). 2021. ↩︎
FBXO31 mutations cause autosomal recessive cerebellar ataxia (Di Fruscio et al. 2015). 2015. ↩︎
Upregulation of FBXO31 in Alzheimer's disease: a neuroprotective response (Santos et al. 2018). 2018. ↩︎
FBXO31 protects dopaminergic neurons in Parkinson's disease models (Chen et al. 2021). 2021. ↩︎