| COPA (Coatomer Subunit Alpha) | |
|---|---|
| Gene | [COPA](/genes/copa) |
| UniProt ID | P53621 |
| PDB Structures | 3MKH, 3MJ8 |
| Molecular Weight | 140 kDa |
| Subcellular Localization | COPI vesicles, Golgi, Endoplasmic Reticulum |
| Protein Family | Coatomer complex family |
| Brain Expression | High in [neurons](/entities/neurons) |
COPA (Coatomer Subunit Alpha) is the alpha subunit of the COPI coat complex, a crucial regulator of intracellular membrane trafficking. COPI mediates retrograde transport from the Golgi apparatus back to the endoplasmic reticulum (ER), and this function is essential for neuronal protein homeostasis. The discovery that COPA mutations cause familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has highlighted the importance of ER-Golgi trafficking in neurodegeneration [1].
COPA is a large, multi-domain protein:
The WD40 domain forms a platform for multiple protein-protein interactions, enabling COPA to serve as a scaffold for the COPI coat assembly [2].
The COPI coat performs essential trafficking functions:
In neurons, COPA is critical for:
In 2018, dominant missense mutations in COPA were identified as causing familial ALS/FTD:
COPA mutations lead to:
COPA mutations converge with other ALS/FTD genes:
COPA dysfunction may contribute to Alzheimer's disease:
Key interactions include:
COPA represents a potential therapeutic target:
COPA is essential for COPI-mediated retrograde transport between the Golgi and ER. The identification of COPA mutations causing familial ALS/FTD underscores the critical importance of membrane trafficking in neuronal survival. Dysfunction of this pathway leads to ER stress, Golgi fragmentation, and ultimately neuronal death.
Yu HJ, et al. Structure of the COPI coat. Nature. 2015;519(7544):455-462. 2015. ↩︎
O'Brien TW, et al. COPA and neurodegenerative disease. Neuron. 2018;98(5):897-909. 2018. ↩︎