BAG6

Description

The BAG6 (BAG cochaperone 6) is a protein-coding gene located on chromosome 6.

BAG6 is an ATP-independent molecular chaperone that prevents the aggregation of misfolded and hydrophobic proteins. It functions as part of the cytosolic BAG6/BAT3 protein quality control complex, which maintains these proteins in a soluble state and delivers them to the endoplasmic reticulum (ER) or targets them for degradation by the proteasome. The complex is involved in post-translational delivery of tail-anchored/type II transmembrane proteins to the ER membrane. BAG6 interacts with the transmembrane region of newly synthesized tail-anchored proteins and, together with SGTA and ASNA1, mediates their delivery to the ER. Proteins that cannot be properly delivered to the ER are ubiquitinated by RNF126 and sorted to the proteasome. SGTA prevents RNF126 recruitment to BAG6, negatively regulating ubiquitination and proteasomal degradation. The BAG6/BAT3 complex also functions as a sorting platform for mislocalized secretory pathway proteins, delivering them to the proteasome or ER. It plays a role in ER-associated degradation (ERAD) by maintaining retrotranslocated proteins in an unfolded yet soluble state in the cytosol, ensuring their proper delivery to the proteasome. BAG6 is required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome, potentially contributing to antigen presentation in immune response. It is involved in ER stress-induced pre-emptive quality control, selectively attenuating protein translocation into the ER and rerouting them to the cytosol for proteasomal degradation. BAG6 may protect the ER from protein overload upon stress. By inhibiting HSPA2 polyubiquitination and proteasomal degradation, it may play a role in synaptonemal complex assembly during spermatogenesis. It positively regulates apoptosis by stabilizing the proapoptotic factor AIFM1. By controlling IGF1R expression, it indirectly regulates insulin-like growth factor receptor signaling. Following DNA damage, BAG6 accumulates in the nucleus, forming a complex with p300/EP300, enhancing p53 acetylation and transcriptional activity. BAG6 may also act as a component of chromatin regulator complexes that regulate histone 3 'Lys-4' dimethylation. It is released extracellularly via exosomes, acting as a ligand for the NK cell receptor NCR3, stimulating NK cell cytotoxicity and triggering cytotoxicity against tumor cells and immature myeloid dendritic cells. It mediates ricin-induced apoptosis.

BAG6 is also known as BAG-6, BAT3, D6S52E, G3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing