CARDIOMETABOLIC

Gene
BAG6

Uniprot
P46379

Protein
Large proline-rich protein BAG6

See alternative names

BAG family molecular chaperone regulator 6,
BCL2-associated athanogene 6,
HLA-B-associated transcript 3,
Protein G3,
Protein Scythe

Uniprot Function Description

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 to 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 to 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).

Involved in DNA damage-induced apoptosis: following DNA damage, accumulates in the nucleus and forms a complex with p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase p53/TP53 transcriptional activity (PubMed:17403783). When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2) (PubMed:18765639).

Mediates ricin-induced apoptosis.

Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC).

Precision

Precision (repeatability) is calculated from linearized NPX values over LOD.

Within run precision Coefficient of Variation (CV)
8%
Between run precision Coefficient of Variation (CV)
10%

Analytical measuring range

The technical data reported below refers to the measured value in the in vitro validation assays run using known concentrations of recombinant antigen. Please note that these figures are for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples.

LOD (pg/ml)
390.6
LLOQ (pg/ml)
781.3
ULOQ (pg/ml)
200000
Hook (pg/ml)
400000
Range (log10)
2.4

Dilution factor

For optimal assay readout, Olink Explore is run using different dilutions of the original samples (undiluted, 1:10, 1:100 or 1:1000). The dilution factor for this assay is noted below and should be taken into account when estimating the appropriate addressable biological concentration of the protein based on the in vitro validation data.

Dilution factor
1:1

Sensitivity plot

The calibrator curve shown below visualizes the analytical measuring range data based on in vitro measurement of recombinant antigen. Please note that this is shown for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples. The vertical dotted lines represent LLOQ and ULOQ respectively, and the horizontal line indicates the LOD. The y-axis shows NPX above background, which is defined as the median of negative control measurements and used to define the expected background level (zero).

Sample distribution plot

The plot below shows the levels of protein measured in a number of commercial plasma samples. Healthy subjects are shown in blue and samples obtained from patients with a range of diseases are shown in red. The latter include inflammatory, cardiovascular, autoimmune & neurological diseases, as well as cancer. The data is shown to give a general idea of the sort of NPX range to expect, but cannot cover all potential levels that may be seen in clinical samples. The y-axis shows NPX above background, which is defined as the median of negative control measurements and used to define the expected background level (zero).