BAG3
Description
The BAG3 (BAG cochaperone 3) is a protein-coding gene located on chromosome 10.
BAG3 is a protein involved in chaperone-assisted selective autophagy. BAG proteins, including BAG3, compete with Hip-1 for binding to the Hsc70/Hsp70 ATPase domain, promoting substrate release. BAG3 contains a WW domain in its N-terminal region and a BAG domain in its C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact with the Hsc70 ATPase domain, inhibiting its chaperone activity. BAG3 has been implicated in age-related neurodegenerative diseases such as Alzheimer's. It regulates both the proteasomal and lysosomal protein elimination pathways and has been linked to familial dilated cardiomyopathy.
BAG3 acts as a co-chaperone for the HSP70 and HSC70 chaperone proteins, facilitating the release of ADP from these proteins and promoting the release of client/substrate proteins. This process involves BAG3 binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 for nucleotide release and the substrate-binding domain (SBD) of HSPA8/HSC70 for substrate release. BAG3 also exhibits anti-apoptotic activity and plays a role in the nucleocytoplasmic transport of HSF1.
BAG3 is also known as BAG-3, BIS, CAIR-1, MFM6.