Bcl2 Associated Athanogene 2 (BAG2)

BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. The predicted BAG2 protein contains 211 amino acids. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner.These authors stated that the functional antagonisms displayed between BAG family proteins and Hip suggest that a proper balance of these 2 types of protein is required for achieving optimal cycles of substrate binding and release required for inducting conformational changes in proteins, with Hip promoting peptide substrate binding by Hsc70/Hsp70 and BAG family proteins promoting dissociation.