| Protein Disulfide Isomerase Family A Member 6 | |
|---|---|
| Gene Symbol | PDIA6 |
| Full Name | Protein Disulfide Isomerase Family A Member 6 |
| Chromosome | 2p25.1 |
| NCBI Gene ID | 10127 |
| OMIM | 612157 |
| Ensembl ID | ENSG00000143870 |
| UniProt ID | Q15020 |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Diabetes |
PDIA6 (Protein Disulfide Isomerase Family A Member 6), also known as ERP29 or P5, is a unique member of the protein disulfide isomerase family that lacks the canonical thioredoxin active site motifs found in other PDI family members.[1] Despite this structural difference, PDIA6 functions as an ER-resident molecular chaperone that assists in protein folding and plays important roles in the unfolded protein response (UPR).[2] PDIA6 is widely expressed across tissues with particularly high levels in brain, lung, and pancreas, where it participates in the maturation of secreted proteins and maintains ER homeostasis.[3] In the context of neurodegenerative diseases, PDIA6 has been implicated in Alzheimer's disease (AD) and Parkinson's disease (PD) through its involvement in ER stress response and protein quality control mechanisms.[4]
PDIA6 functions as a chaperone and assists in protein folding in the endoplasmic reticulum. Unlike classical PDIs, PDIA6 lacks the thioredoxin active site motifs and has distinct client protein specificity. It is involved in the folding of secreted proteins and plays a role in the unfolded protein response (UPR). It can form complexes with other ER chaperones and has anti-apoptotic properties. PDIA6 is phosphorylated in response to stress and can translocate to the nucleus under certain conditions.
PDIA6 is implicated in neurodegenerative diseases through its role in ER homeostasis and protein quality control. In Alzheimer's disease, PDIA6 expression is altered in response to amyloid pathology and may contribute to handling of misfolded proteins. In Parkinson's disease, PDIA6 may help manage ER stress in dopaminergic neurons. Studies have shown that PDIA6 can interact with alpha-synuclein and may be involved in its clearance. Reduced PDIA6 function may contribute to ER stress-mediated neuronal death.
PDIA6 is expressed in most tissues with high expression in brain, lung, and pancreas. In the brain, it is expressed in neurons and glial cells. Expression is upregulated under ER stress conditions and in various disease states.