BAG6: A Protein Involved in Intracellular Signaling Cascades and Cell-cell Adhesion

Target Name: BAG6

NCBI ID: G7917

BAG6: A Protein Involved in Intracellular Signaling Cascades and Cell-cell Adhesion

BAG6 (G3) is a protein that is expressed in various tissues of the body, including the brain, heart, and kidneys. It is a member of the superfamily of transmembrane protein (SMP) family, which includes proteins involved in various cellular processes, including intracellular signaling cascades and cell-cell adhesion.

BAG6 is known for its role in intracellular signaling cascades, particularly in the regulation of theNotch signaling pathway. TheNotch signaling pathway is a critical pathway involved in the regulation of stem cell proliferation and differentiation, and is implicated in various diseases, including cancer, neurodegenerative diseases , and autoimmune diseases.

BAG6 has been shown to play a key role in the regulation of Notch signaling by negatively regulating the activity of the transcription factor SPOP. SPOP is a key regulator of theNotch signaling pathway, and its activity is required for the survival and proliferation of Notch-regulated cells . BAG6 has been shown to physically interact with SPOP and to inhibit its activity by a process called post-translational modification (PTM).

In addition to its role in the regulation of Notch signaling, BAG6 is also involved in the regulation of cell-cell adhesion and in the development of cancer. Studies have shown that BAG6 is a negative regulator of the cadherin gene, which encodes the protein cadherin. Cadherins are important for cell-cell adhesion and are involved in various physiological processes, including tissue repair and regeneration.

BAG6 has also been shown to be involved in the regulation of cell apoptosis, which is the process by which cells die in response to various stimuli, including those that are harmful to the cell. by negatively regulating the activity of the protein BAD. BAD is a negative regulator of the Bcl-2 gene, which encodes the protein Bcl-2. Bcl-2 is a protein that has been shown to play a key role in the regulation of cell apoptosis.

In conclusion, BAG6 is a protein that is involved in various cellular processes and is implicated in the regulation of intracellular signaling cascades, cell-cell adhesion, and cell apoptosis. Its role in these processes makes it a potential drug target and a biomarker for a variety of diseases. Further research is needed to fully understand the mechanisms of BAG6's role in these processes and to develop effective treatments for these diseases.

Protein Name: BAG Cochaperone 6

Functions: ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:21636303). Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20516149, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20516149, PubMed:20676083, PubMed:28104892, PubMed:25535373). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are sorted to the proteasome (PubMed:24981174, PubMed:28104892, PubMed:27193484). SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins (PubMed:23129660, PubMed:25179605, PubMed:27193484). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303). BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response (By similarity). BAG6 is also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. BAG6 may ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress (PubMed:26565908). By inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis (By similarity). Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (By similarity). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333)

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