======= BAG6 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: BAG6
  * **<color #00a2e8>Official Name</color>**: BAG cochaperone 6
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7917|7917]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P46379|P46379]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=BAG6&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20BAG6|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/142590|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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). 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). {ECO:0000250|UniProtKB:Q9Z1R2, ECO:0000269|PubMed:20516149, ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:24981174, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}. 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). {ECO:0000269|PubMed:18055229, ECO:0000269|PubMed:18852879}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|ubiquitin|
|DUF3538|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|protein localization to cytosolic proteasome complex involved in ERAD pathway|
|protein localization to cytosolic proteasome complex|
|endoplasmic reticulum stress-induced pre-emptive quality control|
|maintenance of unfolded protein|
|maintenance of unfolded protein involved in ERAD pathway|
|BAT3 complex|
|tail-anchored membrane protein insertion into ER membrane|
|protein insertion into ER membrane|
|ER-associated misfolded protein catabolic process|
|positive regulation of ERAD pathway|
|proteasome binding|
|ubiquitin-specific protease binding|
|synaptonemal complex assembly|
|synaptonemal complex organization|
|cellular response to misfolded protein|
|misfolded protein binding|
|response to misfolded protein|
|protein quality control for misfolded or incompletely synthesized proteins|
|polyubiquitin modification-dependent protein binding|
|regulation of ERAD pathway|
|intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator|
|intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress|
|negative regulation of proteasomal ubiquitin-dependent protein catabolic process|
|positive regulation of response to endoplasmic reticulum stress|
|protein insertion into membrane|
|Hsp70 protein binding|
|synapsis|
|negative regulation of ubiquitin-dependent protein catabolic process|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|endoplasmic reticulum organization|
|ribosome binding|
|natural killer cell activation|
|homologous chromosome segregation|
|negative regulation of proteasomal protein catabolic process|
|chromosome organization involved in meiotic cell cycle|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|ubiquitin-dependent ERAD pathway|
|negative regulation of proteolysis involved in cellular protein catabolic process|
|regulation of response to endoplasmic reticulum stress|
|negative regulation of cellular protein catabolic process|
|meiotic chromosome segregation|
|ERAD pathway|
|positive regulation of proteasomal protein catabolic process|
|meiosis I|
|meiosis I cell cycle process|
|internal peptidyl-lysine acetylation|
|signal transduction by p53 class mediator|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|peptidyl-lysine acetylation|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|internal protein amino acid acetylation|
|regulation of embryonic development|
|negative regulation of protein catabolic process|
|positive regulation of cellular protein catabolic process|
|protein acetylation|
|cellular response to topologically incorrect protein|
|intrinsic apoptotic signaling pathway|
|meiotic nuclear division|
|regulation of ubiquitin-dependent protein catabolic process|
|meiotic cell cycle process|
|lung development|
|respiratory tube development|
|protein stabilization|
|regulation of proteasomal protein catabolic process|
|response to topologically incorrect protein|
|protein acylation|
|respiratory system development|
|regulation of proteolysis involved in cellular protein catabolic process|
|positive regulation of protein catabolic process|
|nuclear chromosome segregation|
|meiotic cell cycle|
|regulation of cellular protein catabolic process|
|negative regulation of cellular catabolic process|
|response to endoplasmic reticulum stress|
|establishment of protein localization to membrane|
|kidney development|
|chromosome segregation|
|apoptotic signaling pathway|
|renal system development|
|nuclear division|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|negative regulation of catabolic process|
|organelle fission|
|peptidyl-lysine modification|
|urogenital system development|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|signaling receptor binding|
|proteasomal protein catabolic process|
|negative regulation of proteolysis|
|positive regulation of proteolysis|
|positive regulation of cellular catabolic process|
|lymphocyte activation|
|regulation of protein catabolic process|
|endomembrane system organization|
|positive regulation of catabolic process|
|immune response-activating cell surface receptor signaling pathway|
|protein localization to membrane|
|immune response-regulating cell surface receptor signaling pathway|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|spermatogenesis|
|immune response-activating signal transduction|
|male gamete generation|
|proteolysis involved in cellular protein catabolic process|
|immune response-regulating signaling pathway|
|cellular protein catabolic process|
|activation of immune response|
|protein catabolic process|
|intracellular membrane-bounded organelle|
|gamete generation|
|chromatin organization|
|regulation of proteolysis|
|regulation of cellular response to stress|
|protein localization to organelle|
|brain development|
|cellular response to DNA damage stimulus|
|head development|
|multicellular organismal reproductive process|
|sexual reproduction|
|regulation of cellular catabolic process|
|multicellular organism reproduction|
|tube development|
|membrane organization|
|positive regulation of immune response|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|cellular macromolecule catabolic process|
|negative regulation of programmed cell death|
|apoptotic process|
|leukocyte activation|
|central nervous system development|
|negative regulation of cell death|
|multi-organism reproductive process|
|regulation of catabolic process|
|cell cycle process|
|response to organonitrogen compound|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|programmed cell death|
|organonitrogen compound catabolic process|
|chromosome organization|
|cell activation|
|response to nitrogen compound|
|cell death|
|negative regulation of protein metabolic process|
|regulation of immune response|
|positive regulation of immune system process|
|proteolysis|
|cell cycle|
|reproductive process|
|reproduction|
|regulation of response to stress|
|regulation of apoptotic process|
|regulation of programmed cell death|
|cellular protein localization|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|organic substance catabolic process|
|cellular catabolic process|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp354|Diepoxybutane 3μM R07 exp354]]|-2.16|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|-1.81|
|[[:results:exp60|Vinblastine 0.002μM R01 exp60]]|1.87|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|2.44|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.586|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1054
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.05 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='BAG6 Expression in NALM6 Cells: 8.05'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>