BAG3

BAG family molecular chaperone regulator 3 is a is_associated_with::protein that in humans is encoded by the BAG3 is_associated_with::gene. BAG3 is involved in is_associated_with::chaperone-assisted selective autophagy (CASA).

Function
BAG proteins compete with is_associated_with::Hip-1 for binding to the is_associated_with::Hsc70/is_associated_with::Hsp70 is_associated_with::ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid is_associated_with::BAG domain near the is_associated_with::C terminus but differ markedly in their is_associated_with::N-terminal regions. The protein encoded by this gene contains a is_associated_with::WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of is_associated_with::BAG1, is_associated_with::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.

Clinical significance
BAG gene has been implicated in age related neurodegenerative diseases such as is_associated_with::Alzheimer's. It has been demonstrated that BAG1 and BAG 3 regulate the proteasomal and lysosomal protein elimination pathways, respectively. It has also been shown to be the cause of familial dilated cardiomyopathy. That BAG3 mutations are responsible for familial dilated cardiomyopathy is confirmed by another study describing 6 new molecular variants (2 missense and 4 premature Stops ). Moreover, the same publication reported that BAG3 polymorphisms are also associated with sporadic forms of the disease together with HSPB7 locus.

In muscle cells, BAG3 cooperates with the molecular chaperones Hsc70 and HspB8 to induce the degradation of mechanically damaged cytoskeleton components in lysosomes. This process is called is_associated_with::chaperone-assisted selective autophagy (CASA) and is essential for maintaining muscle activity in flies, mice and men.

BAG3 is able to stimulate the expression of is_associated_with::cytoskeleton proteins in response to mechanical tension by activating the transcription regulators is_associated_with::YAP1 and is_associated_with::WWTR1. BAG3 balances protein synthesis and protein degradation under mechanical stress.

Interactions
BAG3 has been shown to interact with:
 * is_associated_with::AMOTL1
 * is_associated_with::Dynein,
 * is_associated_with::HSPA1A,
 * is_associated_with::HSPA8,
 * is_associated_with::LATS1,
 * is_associated_with::PLCG1, and
 * is_associated_with::SYNPO2.