| Gigaxonin (GAN) | |
|---|---|
| Gene | [GAN](/genes/gan) |
| UniProt | Q9H2S0 |
| PDB | 6W5K |
| Mol. Weight | 59 kDa (493 amino acids) |
| Localization | Cytoplasm, cytoskeleton |
| Family | BAG family (BAG3 subfamily) |
| Chromosome | 16q24.1 |
| Diseases | [Giant Axonal Neuropathy (GAN)](/diseases/giant-axonal-neuropathy) |
Gigaxonin is a key E3 ubiquitin ligase adapter protein essential for neuronal survival and function. Mutations in the GAN gene cause Giant Axonal Neuropathy (GAN), a severe autosomal recessive neurodegenerative disorder characterized by progressive motor and sensory neuropathy, along with central nervous system involvement.
Gigaxonin (GAN) is a 59 kDa protein encoded by the GAN gene located on chromosome 16q24.1 [1]. It belongs to the BAG family of co-chaperones, specifically the BAG3 subfamily, which play critical roles in protein quality control and cytoskeletal maintenance [2].
Gigaxonin contains multiple functional domains:
The protein forms a complex with the Cullin-3 (CUL3) ubiquitin ligase to ubiquitinate target proteins for degradation [3].
In the healthy nervous system, gigaxonin plays essential roles in:
GAN is a devastating childhood-onset neurodegenerative disorder caused by recessive loss-of-function mutations in the GAN gene [4]. The disease is characterized by:
While GAN is a rare genetic disorder, understanding gigaxonin function provides insights into common neurodegenerative mechanisms:
Bomont et al. Identification of the gene encoding gigaxonin, a protein related to the ubiquitin-proteasome system (2000). 2000. ↩︎
Carrell & Caplan, Giant axonal neuropathy: a muscle disease? (2005). 2005. ↩︎
Zhang et al. The E3 ligase activity of gigaxonin is essential for its function in protein degradation (2019). 2019. ↩︎
Johnson et al. Giant axonal neuropathy: natural history and clinical features (2010). 2010. ↩︎
Kwon et al. AAV9-mediated gene therapy for giant axonal neuropathy (2020). 2020. ↩︎