Tbio BAG6 Large proline-rich protein BAG6

Protein Summary

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). 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). Mediates ricin-induced apoptosis. This gene was first characterized as part of a cluster of genes located within the human major histocompatibility complex class III region. This gene encodes a nuclear protein that is cleaved by caspase 3 and is implicated in the control of apoptosis. In addition, the protein forms a complex with E1A binding protein p300 and is required for the acetylation of p53 in response to DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P46379
• A2ADJ7
• A3KQ42
• A3KQ44
• A6NGY6
• A6PWF7
• B0UX84
• B4DZ12
• B4E3V4
• E7EMZ4
• F8VXY4
• O95874
• Q5HYL9
• Q5SQ35
• Q5SQ36
• Q5SQ37
• Q5SQ41
• Q5SRP8
• Q5SRP9
• Q5STC1
• Q5STX1
• Q5STX3
• Q96SA6
• Q9BCN4

Gene Name

• BAG6

Ensembl ID

• ENST00000211379
• ENSP00000211379
• ENSG00000204463
• ENST00000361076
• ENSP00000354368
• ENSG00000096155
• ENST00000362049
• ENSP00000354875
• ENST00000375964
• ENSP00000365131
• ENST00000375976
• ENSP00000365143
• ENST00000383446
• ENSP00000372938
• ENST00000383448
• ENSP00000372940
• ENST00000417144
• ENSP00000412110
• ENSG00000229524
• ENST00000419847
• ENSP00000389121
• ENSG00000233348
• ENST00000439687
• ENSP00000402856
• ENST00000442479
• ENSP00000413698
• ENST00000443182
• ENSP00000410156
• ENST00000449450
• ENSP00000397894
• ENST00000451932
• ENSP00000390966
• ENST00000551350
• ENSP00000447546
• ENST00000552116
• ENSP00000447946
• ENST00000552605
• ENSP00000446525
• ENST00000613474
• ENSP00000478966
• ENSG00000227761
• ENST00000615143
• ENSP00000482413
• ENST00000615224
• ENSP00000477951
• ENSG00000228760
• ENST00000615725
• ENSP00000479238
• ENST00000617635
• ENSP00000484238
• ENST00000621056
• ENSP00000477867
• ENSG00000234651

Symbol

• BAT3
• G3
• G3
• BAT3
• BAG-6
• D6S52E

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
disease perturbation	0.97
trait	0.93
biological process	0.86
protein complex	0.83
hub protein	0.82

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Large Proline-rich Protein Bag6

DTO Classes

Protein / Enzyme Modulator / Large Proline-rich Protein Bag6

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 342.17   (req: < 5)

Gene RIFs: 65   (req: <= 3)

Antibodies: 272   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 342.17   (req: >= 5)

Gene RIFs: 65   (req: > 3)

Antibodies: 272   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 37

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0