HSPA1A is a human gene whose product bAG2** (BCL2 Associated Athanogene 2) is a co-chaperone protein that modulates the Hsp70/Hsp90 chaperone systems. It contains a BAG domain that mediates interaction with Hsp70/Hsp90 ATPase domains, regulating their activity in protein folding and quality control. Variants in HSPA1A have been implicated in Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [@bag2020]
BAG2 (BCL2 Associated Athanogene 2) is a co-chaperone protein that modulates the Hsp70/Hsp90 chaperone systems. It contains a BAG domain that mediates interaction with Hsp70/Hsp90 ATPase domains, regulating their activity in protein folding and quality control.
Molecular Function
BAG2 functions as a co-chaperone with multiple roles:
Hsp70 regulation: Binds to the ATPase domain of Hsp70 family proteins (HSPA1A, HSPA8, HSPA5) to regulate their chaperone activity
Hsp90 regulation: Modulates Hsp90 chaperone complex function
Protein quality control: Facilitates targeting of misfolded proteins for degradation
Anti-apoptotic function: BAG family proteins inhibit [apoptosis](/entities/apoptosis) through various mechanisms
Neuroprotection: Protects [neurons](/entities/neurons) from proteotoxic stress
[Unknown, BAG2: A novel tau interactor that promotes tau clearance (Journal of Alzheimer's Disease, 2018) (2018)](https://doi.org/10.3233/JAD-180117)
[Unknown, Hsp70 co-chaperones in neurodegeneration (Cell, 2019) (2019)](https://doi.org/10.1016/j.cell.2019.03.015)
[Unknown, BAG2 regulates autophagy in Parkinson's disease (Autophagy, 2020) (2020)](https://doi.org/10.1080/15548627.2020.1728080)
[Unknown, Targeting BAG2 for ALS therapy (Molecular Neurobiology, 2021) (2021)](https://doi.org/10.1007/s12035-021-02367-0)
[Unknown, The BAG family: Co-chaperones for Hsp70 molecular chaperones (Seminars in Cancer Biology, 2016) (2016)](https://doi.org/10.1016/j.semcancer.2016.01.004)
[Unknown, BAG2 in protein quality control and disease (Cell Stress and Chaperones, 2017) (2017)](https://doi.org/10.1007/s12192-017-0776-9)
Pathway Diagram
The following diagram shows the key molecular relationships involving BAG2 discovered through SciDEX knowledge graph analysis: