PEX10 (Peroxin-10) is a peroxisomal membrane protein essential for peroxisome biogenesis and peroxisomal matrix protein import. Mutations in PEX10 cause peroxisome biogenesis disorders and are linked to neurodegenerative conditions.
| Property | Value |
|----------|-------|
| UniProt ID | O60313 |
| Gene | PEX10 |
| Alternative Names | Peroxin-10, RNF191 |
| Molecular Weight | ~38 kDa |
| Subcellular Localization | Peroxisomal membrane |
| Protein Family | RING finger protein family |
| PDB Structures | Not determined |
PEX10 contains:
- RING finger domain: C3HC4-type zinc finger at N-terminus for E3 ubiquitin ligase activity
- Transmembrane domains: Two predicted TMDs for peroxisomal membrane anchoring
- Cytoplasmic C-terminal tail: Contains the RING domain
The protein functions as part of the peroxisomal targeting signal (PTS) receptor recycling complex.
PEX10 is essential for:
- Peroxisome membrane assembly
- Import of peroxisomal matrix proteins (PTS1 and PTS2)
- Recycling of PTS receptors (PEX5, PEX7)
- Degradation of misfolded peroxisomal proteins
- E3 ubiquitin ligase activity for peroxisomal protein turnover
- ER-associated degradation (ERAD) of peroxisomal membrane proteins
- Regulation of peroxin dynamics
- Very-long-chain fatty acid (VLCFA) oxidation
- Plasmalogen synthesis
- Bile acid intermediate processing
PEX10 mutations cause:
- Neonatal adrenoleukodystrophy (NALD)
- Infantile Refsum disease
- Zellweger syndrome (most severe)
Neurological manifestations include:
- Severe developmental delay
- Hypotonia
- Seizures
- Visual and hearing impairment
- Peroxisomal dysfunction implicated in AD pathogenesis
- Reduced peroxisome numbers in AD brain
- VLCFA accumulation in AD neurons
- Abnormal plasmalogen levels (reduced in AD)
- Peroxisomal function in dopaminergic neurons
- PEX5 and PEX10 mutations linked to PD risk
- Pexophagy defects in PD models
- Lipid dysregulation in PD
- Peroxisomal abnormalities in ALS models
- VLCFA metabolism altered in ALS
- Potential role in motor neuron survival
- Gene therapy for PEX10 mutations
- Small molecules to enhance peroxisome function
- VLCFA-lowering agents
- Blood-brain barrier penetration
- Correcting membrane protein defects
- Balancing peroxisome biogenesis
| Variant |
Effect |
Disease Association |
| R125X |
Truncated protein |
NALD |
| L292P |
Missense |
Zellweger |
| Various |
Missense/nonsense |
Peroxisome biogenesis disorders |