BAG3

BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. 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. [provided by RefSeq, Jul 2008]

Full Name

BCL2 Associated Athanogene 3

Function

Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70 (PubMed:9873016, PubMed:27474739).
Has anti-apoptotic activity (PubMed:10597216).
Plays a role in the HSF1 nucleocytoplasmic transport (PubMed:26159920).

Biological Process

Aggresome assembly Source: ARUK-UCL
Autophagosome assembly Source: Ensembl
Brain development Source: Ensembl
Cellular response to heat Source: UniProtKB
Cellular response to mechanical stimulus Source: Ensembl
Cellular response to unfolded protein Source: ARUK-UCL
Chaperone-mediated autophagy Source: Ensembl
Chaperone-mediated protein transport Source: ARUK-UCL
Extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
Extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
Muscle cell cellular homeostasis Source: ARUK-UCL
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of protein targeting to mitochondrion Source: Ensembl
Negative regulation of striated muscle cell apoptotic process Source: ARUK-UCL
Negative regulation of transcription from RNA polymerase II promoter in response to stress Source: UniProtKB
Positive regulation of aggrephagy Source: ARUK-UCL
Positive regulation of protein export from nucleus Source: UniProtKB
Positive regulation of protein import into nucleus Source: UniProtKB
Protein folding Source: UniProtKB
Protein stabilization Source: ARUK-UCL
Protein transport along microtubule Source: ARUK-UCL
Regulation of cellular response to heat Source: Reactome
Spinal cord development Source: Ensembl

Cellular Location

Cytoplasm; Nucleus. Colocalizes with HSF1 to the nucleus upon heat stress (PubMed:26159920).

Involvement in disease

Myopathy, myofibrillar, 6 (MFM6): A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM6 is characterized by early-onset of severe, progressive, diffuse muscle weakness associated with cardiomyopathy, severe respiratory insufficiency during adolescence, and a rigid spine in some patients.
Cardiomyopathy, dilated 1HH (CMD1HH): A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.