Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Cell Mol Life Sci
2014 May 01;7110:1829-37. doi: 10.1007/s00018-013-1522-y.
Show Gene links
Show Anatomy links
BAG-6, a jack of all trades in health and disease.
Binici J
,
Koch J
.
???displayArticle.abstract??? BCL2-associated athanogene 6 (BAG-6) (also Bat-3/Scythe) was discovered as a gene product of the major histocompatibility complex class III locus. The Xenopus ortholog Scythe was first identified to act as an anti-apoptotic protein. Subsequent studies unraveled that the large BAG-6 protein contributes to a number of cellular processes, including apoptosis, gene regulation, protein synthesis, protein quality control, and protein degradation. In this context, BAG-6 acts as a multifunctional chaperone, which interacts with its target proteins for shuttling to distinct destinations. Nonetheless, as anticipated from its genomic localization, BAG-6 is involved in a variety of immunological pathways such as macrophage function and TH1 response. Most recently, BAG-6 was identified on the plasma membrane of dendritic cells and malignantly transformed cells where it serves as cellular ligand for the activating natural killer (NK) cell receptor NKp30 triggering NK cell cytotoxicity. Moreover, target cells were found to secrete soluble variants of BAG-6 and release BAG-6 on the surface of exosomes, which inhibit or activate NK cell cytotoxicity, respectively. These data suggest that the BAG-6 antigen is an important target to shape a directed immune response or to overcome tumor-immune escape strategies established by soluble BAG-6. This review summarizes the currently known functions of BAG-6, a fascinating multicompetent protein, in health and disease.
Ashiru,
Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes.
2010, Pubmed
Ashiru,
Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes.
2010,
Pubmed
Banerji,
A gene pair from the human major histocompatibility complex encodes large proline-rich proteins with multiple repeated motifs and a single ubiquitin-like domain.
1990,
Pubmed
Binici,
A soluble fragment of the tumor antigen BCL2-associated athanogene 6 (BAG-6) is essential and sufficient for inhibition of NKp30 receptor-dependent cytotoxicity of natural killer cells.
2013,
Pubmed
Chang,
Crystal structure of Get4-Get5 complex and its interactions with Sgt2, Get3, and Ydj1.
2010,
Pubmed
Claessen,
BAT3 guides misfolded glycoproteins out of the endoplasmic reticulum.
2011,
Pubmed
Corduan,
Sequential interplay between BAG6 and HSP70 upon heat shock.
2009,
Pubmed
Degli-Esposti,
Ancestral haplotypes reveal the role of the central MHC in the immunogenetics of IDDM.
1992,
Pubmed
Derrick,
The ESAT6 protein of Mycobacterium tuberculosis induces apoptosis of macrophages by activating caspase expression.
2007,
Pubmed
Desmots,
Scythe regulates apoptosis-inducing factor stability during endoplasmic reticulum stress-induced apoptosis.
2008,
Pubmed
Desmots,
The reaper-binding protein scythe modulates apoptosis and proliferation during mammalian development.
2005,
Pubmed
,
Xenbase
Doong,
What's in the 'BAG'?--A functional domain analysis of the BAG-family proteins.
2002,
Pubmed
Ensminger,
E3 ubiquitin ligase activity and targeting of BAT3 by multiple Legionella pneumophila translocated substrates.
2010,
Pubmed
Fadok,
Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts.
2001,
Pubmed
Ferlazzo,
The interaction between NK cells and dendritic cells in bacterial infections results in rapid induction of NK cell activation and in the lysis of uninfected dendritic cells.
2003,
Pubmed
Fernández-Messina,
Differential mechanisms of shedding of the glycosylphosphatidylinositol (GPI)-anchored NKG2D ligands.
2010,
Pubmed
Groth,
Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance.
2011,
Pubmed
Grover,
BAT3 regulates Mycobacterium tuberculosis protein ESAT-6-mediated apoptosis of macrophages.
2012,
Pubmed
Hamza,
Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.
2010,
Pubmed
Harney,
Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis.
2008,
Pubmed
Hessa,
Protein targeting and degradation are coupled for elimination of mislocalized proteins.
2011,
Pubmed
Hirsch,
The ubiquitylation machinery of the endoplasmic reticulum.
2009,
Pubmed
Hsieh,
Human lymphocyte antigen B-associated transcript 2, 3, and 5 polymorphisms and haplotypes are associated with susceptibility of Kawasaki disease and coronary artery aneurysm.
2010,
Pubmed
Ivanov,
Identifying candidate colon cancer tumor suppressor genes using inhibition of nonsense-mediated mRNA decay in colon cancer cells.
2007,
Pubmed
Kagan,
A role for oxidative stress in apoptosis: oxidation and externalization of phosphatidylserine is required for macrophage clearance of cells undergoing Fas-mediated apoptosis.
2002,
Pubmed
Khan,
Cutting edge: neosynthesis is required for the presentation of a T cell epitope from a long-lived viral protein.
2001,
Pubmed
Kikukawa,
Unique proteasome subunit Xrpn10c is a specific receptor for the antiapoptotic ubiquitin-like protein Scythe.
2005,
Pubmed
,
Xenbase
Koch,
The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation.
2006,
Pubmed
Koch,
Activating natural cytotoxicity receptors of natural killer cells in cancer and infection.
2013,
Pubmed
Krenciute,
Nuclear BAG6-UBL4A-GET4 complex mediates DNA damage signaling and cell death.
2013,
Pubmed
Kwak,
BAT3 interacts with transforming growth factor-beta (TGF-beta) receptors and enhances TGF-beta1-induced type I collagen expression in mesangial cells.
2008,
Pubmed
Kämper,
A novel BAT3 sequence generated by alternative RNA splicing of exon 11B displays cell type-specific expression and impacts on subcellular localization.
2012,
Pubmed
Kämper,
γ-Interferon-regulated chaperone governs human lymphocyte antigen class II expression.
2012,
Pubmed
Leznicki,
Bat3 promotes the membrane integration of tail-anchored proteins.
2010,
Pubmed
Liao,
The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines.
2001,
Pubmed
Manchen,
Human Scythe contains a functional nuclear localization sequence and remains in the nucleus during staurosporine-induced apoptosis.
2001,
Pubmed
Mariappan,
The mechanism of membrane-associated steps in tail-anchored protein insertion.
2011,
Pubmed
Mariappan,
A ribosome-associating factor chaperones tail-anchored membrane proteins.
2010,
Pubmed
Metzger,
Degradation of a cytosolic protein requires endoplasmic reticulum-associated degradation machinery.
2008,
Pubmed
Minami,
Scythe regulates apoptosis through modulating ubiquitin-mediated proteolysis of the Xenopus elongation factor XEF1AO.
2007,
Pubmed
,
Xenbase
Minami,
BAG-6 is essential for selective elimination of defective proteasomal substrates.
2010,
Pubmed
Naishiro,
BAG-1 accelerates cell motility of human gastric cancer cells.
1999,
Pubmed
Nguyen,
BAT3 and SET1A form a complex with CTCFL/BORIS to modulate H3K4 histone dimethylation and gene expression.
2008,
Pubmed
Pai,
Regulation of class II MHC expression in APCs: roles of types I, III, and IV class II transactivator.
2002,
Pubmed
Pogge von Strandmann,
Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells.
2007,
Pubmed
Preta,
Scythe cleavage during Fas (APO-1)-and staurosporine-mediated apoptosis.
2012,
Pubmed
Preta,
AIF and Scythe (Bat3) regulate phosphatidylserine exposure and macrophage clearance of cells undergoing Fas (APO-1)-mediated apoptosis.
2012,
Pubmed
Rabu,
Biogenesis of tail-anchored proteins: the beginning for the end?
2009,
Pubmed
Rangachari,
Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion.
2012,
Pubmed
Reiners,
Soluble ligands for NK cell receptors promote evasion of chronic lymphocytic leukemia cells from NK cell anti-tumor activity.
2013,
Pubmed
Reiners,
Rescue of impaired NK cell activity in hodgkin lymphoma with bispecific antibodies in vitro and in patients.
2013,
Pubmed
Reits,
The major substrates for TAP in vivo are derived from newly synthesized proteins.
2000,
Pubmed
Rosati,
BAG3: a multifaceted protein that regulates major cell pathways.
2011,
Pubmed
Sasaki,
Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis.
2008,
Pubmed
Sasaki,
HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53.
2007,
Pubmed
Schuldiner,
The GET complex mediates insertion of tail-anchored proteins into the ER membrane.
2008,
Pubmed
Simhadri,
Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function.
2008,
Pubmed
Stefanovic,
Identification of a targeting factor for posttranslational membrane protein insertion into the ER.
2007,
Pubmed
Takayama,
Molecular chaperone targeting and regulation by BAG family proteins.
2001,
Pubmed
Tang,
Expression of BAG-1 in invasive breast carcinomas.
1999,
Pubmed
Thress,
Reaper-induced dissociation of a Scythe-sequestered cytochrome c-releasing activity.
1999,
Pubmed
,
Xenbase
Thress,
Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper.
2001,
Pubmed
,
Xenbase
Thress,
Scythe: a novel reaper-binding apoptotic regulator.
1998,
Pubmed
,
Xenbase
Trajkovic,
Ceramide triggers budding of exosome vesicles into multivesicular endosomes.
2008,
Pubmed
Ullrich,
New prospects on the NKG2D/NKG2DL system for oncology.
2013,
Pubmed
Vandiedonck,
Pleiotropic effects of the 8.1 HLA haplotype in patients with autoimmune myasthenia gravis and thymus hyperplasia.
2004,
Pubmed
Wakeman,
Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases.
2012,
Pubmed
Wang,
A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation.
2011,
Pubmed
Wang,
Common 5p15.33 and 6p21.33 variants influence lung cancer risk.
2008,
Pubmed
Winnefeld,
Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest.
2006,
Pubmed
Wu,
Regulation of apoptosis by Bat3-enhanced YWK-II/APLP2 protein stability.
2012,
Pubmed
Wu,
Ricin triggers apoptotic morphological changes through caspase-3 cleavage of BAT3.
2004,
Pubmed
Xu,
SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation.
2012,
Pubmed
Xu,
A ubiquitin-like domain recruits an oligomeric chaperone to a retrotranslocation complex in endoplasmic reticulum-associated degradation.
2013,
Pubmed
Zhu,
The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity.
2005,
Pubmed
