| DNAJC6 | |
|---|---|
| Full Name | Auxilin-1 |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | [98331](https://www.ncbi.nlm.nih.gov/gene/98331) |
| OMIM | [613399](https://www.omim.org/entry/613399) |
| UniProt ID | [Q9H3Z4](https://www.uniprot.org/uniprotkb/Q9H3Z4) |
| Ensembl ID | [ENSG00000138193](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138193) |
| Category | Molecular Chaperone |
| Protein | [Auxilin-1](/proteins/auxilin-1) |
DNAJC6 (DnaJ Heat Shock Protein Family Member C6), also known as Auxilin-1, is a neuronal co-chaperone specifically involved in clathrin-mediated endocytosis. Auxilin recognizes clathrin-coated vesicles and recruits Hsc70 to facilitate clathrin cage disassembly. It contains a J-domain for Hsc70 interaction and a phosphoinositide-binding domain for membrane association. Beyond endocytosis, auxilin is critically involved in synaptic vesicle recycling and neuronal signaling.
DNAJC6 is one of the few genes where recessive loss-of-function mutations cause early-onset Parkinson's disease, highlighting the importance of endocytic trafficking in dopaminergic neuron survival.
DNAJC6 encodes auxilin-1, a neuronal co-chaperone specifically involved in clathrin-mediated endocytosis. The protein performs several critical functions:
In presynaptic terminals, auxilin is essential for:
| Partner | Interaction Type | Function |
|---|---|---|
| Clathrin | Direct binding | Clathrin coat component |
| Hsc70 | J-domain mediated | Chaperone for disassembly |
| Cyclin G-associated kinase (GAK) | Synergistic | Auxilin-like function in non-neuronal cells |
| Dynamin | Functional | Membrane fission during endocytosis |
| Aspect | Details |
|---|---|
| Inheritance | Autosomal recessive |
| Onset | Early-onset (typically before age 40) |
| Phenotype | Progressive parkinsonism with good levodopa response |
| Mechanism | Loss of auxilin function → impaired endocytosis → synaptic vesicle recycling deficits → dopaminergic neuron degeneration |
| Pathology | Loss of dopaminergic neurons in substantia nigra pars compacta |
DNAJC6 mutations lead to synaptic vesicle recycling deficits and dopaminergic neuron degeneration. Patients typically present with:
Studies in:
DNAJC6 is expressed almost exclusively in the brain, with highest expression in:
It is localized to presynaptic terminals where clathrin-mediated endocytosis is highly active. Expression is neuron-specific.