ID:BAG6_HUMAN DESCRIPTION: RecName: Full=Large proline-rich protein BAG6; AltName: Full=BAG family molecular chaperone regulator 6; AltName: Full=BCL2-associated athanogene 6; Short=BAG-6; Short=BAG6; AltName: Full=HLA-B-associated transcript 3; AltName: Full=Protein G3; AltName: Full=Protein Scythe; FUNCTION: Chaperone that plays a key role in various processes such as apoptosis, insertion of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane and regulation of chromatin. Acts in part by regulating stability of proteins and their degradation by the proteasome. Participates in endoplasmic reticulum stress-induced apoptosis via its interaction with AIFM1/AIF by regulating AIFM1/AIF stability and preventing its degradation. Also required during spermatogenesis for synaptonemal complex assembly via its interaction with HSPA2, by inhibiting polyubiquitination and subsequent proteasomal degradation of HSPA2. Required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, may play a role in immuno-proteasomes to generate antigenic peptides via targeted degradation, thereby playing a role in antigen presentation in immune response. Key component of the BAG6/BAT3 complex, a cytosolic multiprotein complex involved in the post-translational delivery of tail-anchored (TA) membrane proteins to the endoplasmic reticulum membrane. TA membrane proteins, also named type II transmembrane proteins, contain a single C-terminal transmembrane region. BAG6/BAT3 acts by facilitating TA membrane proteins capture by ASNA1/TRC40: it is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane region of newly released TA proteins and transfers them to ASNA1/TRC40 for targeting to the endoplasmic reticulum membrane. FUNCTION: 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. When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2). FUNCTION: Can be released from tumor and dendritic cells in membrane vesicles or exosomes, and engage NCR3 thereby promoting natural killer cell (NK) activation and cytotoxicity. SUBUNIT: Component of the BAT3 complex, at least composed of BAG6/BAT3, UBL4A and GET3/TRC35. Interacts with AIFM1, CTCFL, HSPA2 and p300/EP300. Interacts with ricin A chain. Interacts with L.pneumophila proteins Lpg2160 and LegU1. Interacts with NCR3. INTERACTION: Q7Z434:MAVS; NbExp=2; IntAct=EBI-347552, EBI-995373; SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus. Note=The C- terminal fragment generated by caspase-3 is cytoplasmic. Also found in extracellular vesicular exosomes in some tumor cells. PTM: Cleavage by caspase-3 releases a C-terminal peptide that plays a role in ricin-induced apoptosis. PTM: In case of infection by L.pneumophila, ubiquitinated by the SCF(LegU1) complex. SIMILARITY: Contains 1 ubiquitin-like domain. SEQUENCE CAUTION: Sequence=AAD18085.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAB63390.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAI18318.2; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P46379
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001822 kidney development GO:0002376 immune system process GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0006325 chromatin organization GO:0006511 ubiquitin-dependent protein catabolic process GO:0006915 apoptotic process GO:0007130 synaptonemal complex assembly GO:0007283 spermatogenesis GO:0007420 brain development GO:0009790 embryo development GO:0010498 proteasomal protein catabolic process GO:0018393 internal peptidyl-lysine acetylation GO:0030101 natural killer cell activation GO:0030154 cell differentiation GO:0030324 lung development GO:0030433 ER-associated ubiquitin-dependent protein catabolic process GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0042127 regulation of cell proliferation GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0042981 regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0045861 negative regulation of proteolysis GO:0050821 protein stabilization GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0071712 ER-associated misfolded protein catabolic process GO:0071816 tail-anchored membrane protein insertion into ER membrane GO:1904294 positive regulation of ERAD pathway GO:1904378 maintenance of unfolded protein involved in ERAD pathway GO:1904379 protein localization to cytosolic proteasome complex involved in ERAD pathway
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
