Q9Z1R2 · BAG6_MOUSE
- ProteinLarge proline-rich protein BAG6
- GeneBag6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1154 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:18056262, PubMed:18678708, PubMed:20713601).
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 in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20713601).
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. 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. SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins. 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. 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 (By similarity).
BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response (PubMed:20713601).
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 (By similarity).
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 (PubMed:18678708).
Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (PubMed:18056262).
By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (By similarity).
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 in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20713601).
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. 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. SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins. 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. 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 (By similarity).
BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response (PubMed:20713601).
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 (By similarity).
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 (PubMed:18678708).
Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (PubMed:18056262).
By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (By similarity).
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).
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).
May mediate ricin-induced apoptosis.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 1023-1024 | Cleavage; by CASP3 | ||||
Sequence: DG |
GO annotations
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameLarge proline-rich protein BAG6
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9Z1R2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Normally localized in cytosol and nucleus, it can also be released extracellularly, in exosomes, by tumor and myeloid dendritic cells.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Lethality associated with pronounced developmental defects in the lung, kidney and brain. Lethality is either embryonic consecutive to abnormal brain development or perinatal associated with pronounced developmental defects in the lung and kidney. These developmental defects were associated with widespread aberrant apoptosis and proliferation. Lethality can be partially rescued in an ICR genetic background: mice are slightly smaller in size than their wild-type counterparts and show impaired genotoxic stress responses.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 63 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000114898 | 1-1154 | Large proline-rich protein BAG6 | |||
Sequence: MEPSDSASTAMEEPDSLEVLVKTLDSQTRTFIVGAQMNVKEFKEHIAASVSIPSEKQRLIYQGRVLQDDKKLQEYNVGGKVIHLVERAPPQTQLPSGASSGTGSASATHGGAPLPGTRGPGASVHDRNANSYVMVGTFNLPSDGSAVDVHINMEQAPIQSEPRVRLVMAQHMIRDIQTLLSRMECRGGTQAQASQPPPQTPQTVASETVALNSQTSEPVESEAPPREPMESEEMEERPPTQTPELAPSGPAPAGPAPAGPAPAPETNAPNHPSPAEHVEVLQELQRLQRRLQPFLQRYCEVLGAAATTDYNNNHEGREEDQRLINLVGESLRLLGNTFVALSDLRCNLACAPPRHLHVVRPMSHYTTPMVLQQAAIPIQINVGTTVTMTGNGARPPPAPGAEAATPGSAQATSLPPSSTTVDSSTEGAPPPGPAPPPASSHPRVIRISHQSVEPVVMMHMNIQDSGAQPGGVPSAPTGPLGPPGHGQTLGQQVPGFPTAPTRVVIARPTPPQARPSHPGGPPVSGALQGAGLGTNTSLAQMVSGLVGQLLMQPVLVAQGTPGMAQAQAQAQAQAQAQAQAPAPAPAPAPAPATASASAGTTNTATTAGPAPGGPAQPPPPQPSAADLQFSQLLGNLLGPAGPGAGGPGMASPTITVAMPGVPAFLQGMTDFLQASQTAPPPPPPPPPPPPAPEQQSTPPPGSPSGGTASPGGLGPESLPPEFFTSVVQGVLSSLLGSLGARAGSSESIAAFIQRLSGSSNIFEPGADGALGFFGALLSLLCQNFSMVDVVMLLHGHFQPLQRLQPQLRSFFHQHYLGGQEPTPSNIRMATHTLITGLEEYVRESFSLVQVQPGVDIIRTNLEFLQEQFNSIAAHVLHCTDSGFGARLLELCNQGLFECLALNLHCLGGQQMELAAVINGRIRRMSRGVNPSLVSWLTTMMGLRLQVVLEHMPVGPDAILRYVRRVGDPPQTLPEEPMEVQGAERTSPEPQRENASPAPGTTAEEAMSRGPPPAPEGGSRDEQDGASADAEPWAAAVPPEWVPIIQQDIQSQRKVKPQPPLSDAYLSGMPAKRRKTMQGEGPQLLLSEAVSRAAKAAGARPLTSPESLSRDLEAPEVQESYRQQLRSDIQKRLQEDPNYSPQRFPNAHRAFADDP | ||||||
Modified residue | 96 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 117 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 986 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 995 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1075 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1103 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1139 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ricin can induce a cleavage by the caspase CASP3. The released C-terminal peptide induces apoptosis.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Component of the BAG6/BAT3 complex, also named BAT3 complex, at least composed of BAG6, UBL4A and GET4/TRC35. Interacts with GET4; the interaction is direct and localizes BAG6 in the cytosol (By similarity).
Interacts with UBL4A; the interaction is direct and required for UBL4A protein stability (By similarity).
Interacts with AIFM1 (PubMed:18056262).
Interacts with HSPA2 (PubMed:18678708).
Interacts with CTCFL. Interacts with p300/EP300. Interacts (via ubiquitin-like domain) with RNF126; required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol. Interacts (via ubiquitin-like domain) with SGTA; SGTA competes with RNF126 by binding the same region of BAG6, thereby promoting deubiquitination of BAG6-target proteins and rescuing them from degradation. Interacts with ricin A chain. Interacts with VCP and AMFR; both form the VCP/p97-AMFR/gp78 complex. Interacts with SYVN1. Interacts with USP13; the interaction is direct and may mediate UBL4A deubiquitination (By similarity).
Interacts with ZFAND2B (PubMed:24160817, PubMed:26337389, PubMed:26876100).
Interacts with KPNA2 (By similarity).
Interacts with UBQLN4 (By similarity).
Interacts with UBL4A; the interaction is direct and required for UBL4A protein stability (By similarity).
Interacts with AIFM1 (PubMed:18056262).
Interacts with HSPA2 (PubMed:18678708).
Interacts with CTCFL. Interacts with p300/EP300. Interacts (via ubiquitin-like domain) with RNF126; required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol. Interacts (via ubiquitin-like domain) with SGTA; SGTA competes with RNF126 by binding the same region of BAG6, thereby promoting deubiquitination of BAG6-target proteins and rescuing them from degradation. Interacts with ricin A chain. Interacts with VCP and AMFR; both form the VCP/p97-AMFR/gp78 complex. Interacts with SYVN1. Interacts with USP13; the interaction is direct and may mediate UBL4A deubiquitination (By similarity).
Interacts with ZFAND2B (PubMed:24160817, PubMed:26337389, PubMed:26876100).
Interacts with KPNA2 (By similarity).
Interacts with UBQLN4 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Z1R2 | Camk2a P11798-2 | 3 | EBI-644645, EBI-400402 | |
BINARY | Q9Z1R2 | Tnfrsf11a O35305 | 4 | EBI-644645, EBI-647362 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias, repeat, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 17-92 | Ubiquitin-like | ||||
Sequence: LEVLVKTLDSQTRTFIVGAQMNVKEFKEHIAASVSIPSEKQRLIYQGRVLQDDKKLQEYNVGGKVIHLVERAPPQT | ||||||
Region | 87-125 | Disordered | ||||
Sequence: RAPPQTQLPSGASSGTGSASATHGGAPLPGTRGPGASVH | ||||||
Compositional bias | 92-107 | Polar residues | ||||
Sequence: TQLPSGASSGTGSASA | ||||||
Compositional bias | 186-220 | Polar residues | ||||
Sequence: RGGTQAQASQPPPQTPQTVASETVALNSQTSEPVE | ||||||
Region | 186-274 | Disordered | ||||
Sequence: RGGTQAQASQPPPQTPQTVASETVALNSQTSEPVESEAPPREPMESEEMEERPPTQTPELAPSGPAPAGPAPAGPAPAPETNAPNHPSP | ||||||
Compositional bias | 223-239 | Basic and acidic residues | ||||
Sequence: APPREPMESEEMEERPP | ||||||
Repeat | 237-271 | 1 | ||||
Sequence: RPPTQTPELAPSGPAPAGPAPAGPAPAPETNAPNH | ||||||
Region | 237-658 | 4 X 29 AA approximate repeats | ||||
Sequence: RPPTQTPELAPSGPAPAGPAPAGPAPAPETNAPNHPSPAEHVEVLQELQRLQRRLQPFLQRYCEVLGAAATTDYNNNHEGREEDQRLINLVGESLRLLGNTFVALSDLRCNLACAPPRHLHVVRPMSHYTTPMVLQQAAIPIQINVGTTVTMTGNGARPPPAPGAEAATPGSAQATSLPPSSTTVDSSTEGAPPPGPAPPPASSHPRVIRISHQSVEPVVMMHMNIQDSGAQPGGVPSAPTGPLGPPGHGQTLGQQVPGFPTAPTRVVIARPTPPQARPSHPGGPPVSGALQGAGLGTNTSLAQMVSGLVGQLLMQPVLVAQGTPGMAQAQAQAQAQAQAQAQAPAPAPAPAPAPATASASAGTTNTATTAGPAPGGPAQPPPPQPSAADLQFSQLLGNLLGPAGPGAGGPGMASPTITVAM | ||||||
Compositional bias | 243-269 | Pro residues | ||||
Sequence: PELAPSGPAPAGPAPAGPAPAPETNAP | ||||||
Region | 387-442 | Disordered | ||||
Sequence: TMTGNGARPPPAPGAEAATPGSAQATSLPPSSTTVDSSTEGAPPPGPAPPPASSHP | ||||||
Compositional bias | 406-426 | Polar residues | ||||
Sequence: PGSAQATSLPPSSTTVDSSTE | ||||||
Repeat | 416-444 | 2 | ||||
Sequence: PSSTTVDSSTEGAPPPGPAPPPASSHPRV | ||||||
Region | 463-531 | Disordered | ||||
Sequence: QDSGAQPGGVPSAPTGPLGPPGHGQTLGQQVPGFPTAPTRVVIARPTPPQARPSHPGGPPVSGALQGAG | ||||||
Region | 568-626 | Disordered | ||||
Sequence: AQAQAQAQAQAQAPAPAPAPAPAPATASASAGTTNTATTAGPAPGGPAQPPPPQPSAAD | ||||||
Compositional bias | 594-609 | Polar residues | ||||
Sequence: ASASAGTTNTATTAGP | ||||||
Repeat | 597-624 | 3 | ||||
Sequence: SAGTTNTATTAGPAPGGPAQPPPPQPSA | ||||||
Repeat | 630-658 | 4 | ||||
Sequence: SQLLGNLLGPAGPGAGGPGMASPTITVAM | ||||||
Region | 673-719 | Disordered | ||||
Sequence: QASQTAPPPPPPPPPPPPAPEQQSTPPPGSPSGGTASPGGLGPESLP | ||||||
Compositional bias | 676-705 | Pro residues | ||||
Sequence: QTAPPPPPPPPPPPPAPEQQSTPPPGSPSG | ||||||
Region | 968-1154 | Disordered | ||||
Sequence: PPQTLPEEPMEVQGAERTSPEPQRENASPAPGTTAEEAMSRGPPPAPEGGSRDEQDGASADAEPWAAAVPPEWVPIIQQDIQSQRKVKPQPPLSDAYLSGMPAKRRKTMQGEGPQLLLSEAVSRAAKAAGARPLTSPESLSRDLEAPEVQESYRQQLRSDIQKRLQEDPNYSPQRFPNAHRAFADDP | ||||||
Region | 1032-1062 | Required for interaction with GET4 | ||||
Sequence: WAAAVPPEWVPIIQQDIQSQRKVKPQPPLSD | ||||||
Motif | 1034-1076 | Nuclear localization site | ||||
Sequence: AAVPPEWVPIIQQDIQSQRKVKPQPPLSDAYLSGMPAKRRKTM | ||||||
Region | 1044-1154 | Sufficient for the delivery of client proteins to the endoplasmic reticulum | ||||
Sequence: IQQDIQSQRKVKPQPPLSDAYLSGMPAKRRKTMQGEGPQLLLSEAVSRAAKAAGARPLTSPESLSRDLEAPEVQESYRQQLRSDIQKRLQEDPNYSPQRFPNAHRAFADDP | ||||||
Region | 1080-1137 | BAG-similar domain, required and sufficient for interaction with UBL4A | ||||
Sequence: GPQLLLSEAVSRAAKAAGARPLTSPESLSRDLEAPEVQESYRQQLRSDIQKRLQEDPN |
Domain
The ubiquitin-like domain mediates interaction with the E3 ubiquitin-protein ligase RNF126 which is responsible for the BAG6-dependent ubiquitination of client proteins. SGTA also binds this domain and competes with RNF126 to antagonize client protein ubiquitination and degradation. The ubiquitin-like domain also mediates the interaction with USP13.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,154
- Mass (Da)121,037
- Last updated1999-05-01 v1
- Checksum7F3FD14DF5AC1211
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 92-107 | Polar residues | ||||
Sequence: TQLPSGASSGTGSASA | ||||||
Compositional bias | 186-220 | Polar residues | ||||
Sequence: RGGTQAQASQPPPQTPQTVASETVALNSQTSEPVE | ||||||
Compositional bias | 223-239 | Basic and acidic residues | ||||
Sequence: APPREPMESEEMEERPP | ||||||
Compositional bias | 243-269 | Pro residues | ||||
Sequence: PELAPSGPAPAGPAPAGPAPAPETNAP | ||||||
Compositional bias | 406-426 | Polar residues | ||||
Sequence: PGSAQATSLPPSSTTVDSSTE | ||||||
Sequence conflict | 528 | in Ref. 3; AAH26647 | ||||
Sequence: Missing | ||||||
Compositional bias | 594-609 | Polar residues | ||||
Sequence: ASASAGTTNTATTAGP | ||||||
Compositional bias | 676-705 | Pro residues | ||||
Sequence: QTAPPPPPPPPPPPPAPEQQSTPPPGSPSG | ||||||
Sequence conflict | 1012 | in Ref. 3; AAH26647 | ||||
Sequence: P → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF109719 EMBL· GenBank· DDBJ | AAC82479.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CR974444 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC026647 EMBL· GenBank· DDBJ | AAH26647.1 EMBL· GenBank· DDBJ | mRNA |