UniProtKB - Q9Z1R2 (BAG6_MOUSE)
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Protein
Large proline-rich protein BAG6
Gene
Bag6
Organism
Mus musculus (Mouse)
Status
Functioni
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 to 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 to 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 similarity3 Publications
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).By similarity
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).By similarity
May mediate ricin-induced apoptosis.By similarity
GO - Molecular functioni
- Hsp70 protein binding Source: UniProtKB
- identical protein binding Source: MGI
- misfolded protein binding Source: MGI
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- proteasome binding Source: UniProtKB
- receptor binding Source: MGI
- ribosome binding Source: UniProtKB
- ubiquitin protein ligase binding Source: MGI
- ubiquitin-specific protease binding Source: MGI
GO - Biological processi
- antigen processing and presentation of peptide antigen via MHC class I Source: UniProtKB
- apoptotic process Source: UniProtKB
- brain development Source: UniProtKB
- cell differentiation Source: UniProtKB-KW
- chromatin organization Source: UniProtKB-KW
- embryo development Source: UniProtKB
- endoplasmic reticulum stress-induced pre-emptive quality control Source: UniProtKB
- ER-associated misfolded protein catabolic process Source: UniProtKB
- immune response-activating cell surface receptor signaling pathway Source: MGI
- internal peptidyl-lysine acetylation Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
- kidney development Source: UniProtKB
- lung development Source: UniProtKB
- maintenance of unfolded protein involved in ERAD pathway Source: MGI
- natural killer cell activation Source: MGI
- negative regulation of apoptotic process Source: MGI
- negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
- negative regulation of proteolysis Source: UniProtKB
- positive regulation of ERAD pathway Source: MGI
- proteasomal protein catabolic process Source: UniProtKB
- protein stabilization Source: UniProtKB
- regulation of apoptotic process Source: UniProtKB
- regulation of cell proliferation Source: Ensembl
- spermatogenesis Source: UniProtKB
- synaptonemal complex assembly Source: UniProtKB
- tail-anchored membrane protein insertion into ER membrane Source: UniProtKB
- ubiquitin-dependent ERAD pathway Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: UniProtKB
Keywordsi
Molecular function | Chaperone, Chromatin regulator |
Biological process | Apoptosis, Differentiation, Immunity, Spermatogenesis, Transport |
Names & Taxonomyi
Protein namesi | Recommended name: Large proline-rich protein BAG6CuratedAlternative name(s): BAG family molecular chaperone regulator 6 BCL2-associated athanogene 6Imported Short name: BAG-61 Publication HLA-B-associated transcript 31 Publication Protein Scythe1 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1919439 Bag6 |
Pathology & Biotechi
Disruption phenotypei
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.2 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000114898 | 1 – 1154 | Large proline-rich protein BAG6Add BLAST | 1154 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Modified residuei | 96 | PhosphoserineBy similarity | 1 | |
Modified residuei | 117 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 986 | PhosphoserineBy similarity | 1 | |
Modified residuei | 995 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1075 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1103 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1139 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Ricin can induce a cleavage by the caspase CASP3. The released C-terminal peptide induces apoptosis.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 1023 – 1024 | Cleavage; by CASP3By similarity | 2 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q9Z1R2 |
MaxQBi | Q9Z1R2 |
PaxDbi | Q9Z1R2 |
PRIDEi | Q9Z1R2 |
PTM databases
iPTMneti | Q9Z1R2 |
PhosphoSitePlusi | Q9Z1R2 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000024392 |
CleanExi | MM_BAT3 |
ExpressionAtlasi | Q9Z1R2 baseline and differential |
Genevisiblei | Q9Z1R2 MM |
Interactioni
Subunit structurei
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 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).By similarity2 Publications
Binary interactionsi
GO - Molecular functioni
- Hsp70 protein binding Source: UniProtKB
- identical protein binding Source: MGI
- misfolded protein binding Source: MGI
- polyubiquitin modification-dependent protein binding Source: UniProtKB
- receptor binding Source: MGI
- ubiquitin protein ligase binding Source: MGI
- ubiquitin-specific protease binding Source: MGI
Protein-protein interaction databases
BioGridi | 2303097 interactors. |
DIPi | DIP-49391N |
IntActi | Q9Z1R2 8 interactors. |
MINTi | Q9Z1R2 |
STRINGi | 10090.ENSMUSP00000025250 |
Structurei
3D structure databases
ProteinModelPortali | Q9Z1R2 |
SMRi | Q9Z1R2 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 17 – 92 | Ubiquitin-likePROSITE-ProRule annotationAdd BLAST | 76 | |
Repeati | 237 – 271 | 1By similarityAdd BLAST | 35 | |
Repeati | 416 – 444 | 2By similarityAdd BLAST | 29 | |
Repeati | 597 – 624 | 3By similarityAdd BLAST | 28 | |
Repeati | 630 – 658 | 4By similarityAdd BLAST | 29 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 237 – 658 | 4 X 29 AA approximate repeatsBy similarityAdd BLAST | 422 | |
Regioni | 1044 – 1154 | Mediates interaction with UBL4A and GET4 and is sufficient for the delivery of client proteins to the endoplasmic reticulumBy similarityAdd BLAST | 111 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 196 – 274 | Pro-richPROSITE-ProRule annotationAdd BLAST | 79 | |
Compositional biasi | 395 – 720 | Pro-richPROSITE-ProRule annotationAdd BLAST | 326 | |
Compositional biasi | 564 – 610 | Ala-richAdd BLAST | 47 |
Domaini
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.By similarity
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG4248 Eukaryota ENOG410XS9P LUCA |
GeneTreei | ENSGT00390000016199 |
HOVERGENi | HBG002193 |
InParanoidi | Q9Z1R2 |
OMAi | PMVAPNA |
OrthoDBi | EOG091G0XSR |
PhylomeDBi | Q9Z1R2 |
TreeFami | TF328437 |
Family and domain databases
InterProi | View protein in InterPro IPR021925 BAG6 IPR029071 Ubiquitin-like_domsf IPR019954 Ubiquitin_CS IPR000626 Ubiquitin_dom |
Pfami | View protein in Pfam PF12057 DUF3538, 1 hit PF00240 ubiquitin, 1 hit |
SMARTi | View protein in SMART SM00213 UBQ, 1 hit |
SUPFAMi | SSF54236 SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS00299 UBIQUITIN_1, 1 hit PS50053 UBIQUITIN_2, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9Z1R2-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEPSDSASTA MEEPDSLEVL VKTLDSQTRT FIVGAQMNVK EFKEHIAASV
60 70 80 90 100
SIPSEKQRLI YQGRVLQDDK KLQEYNVGGK VIHLVERAPP QTQLPSGASS
110 120 130 140 150
GTGSASATHG GAPLPGTRGP GASVHDRNAN SYVMVGTFNL PSDGSAVDVH
160 170 180 190 200
INMEQAPIQS EPRVRLVMAQ HMIRDIQTLL SRMECRGGTQ AQASQPPPQT
210 220 230 240 250
PQTVASETVA LNSQTSEPVE SEAPPREPME SEEMEERPPT QTPELAPSGP
260 270 280 290 300
APAGPAPAGP APAPETNAPN HPSPAEHVEV LQELQRLQRR LQPFLQRYCE
310 320 330 340 350
VLGAAATTDY NNNHEGREED QRLINLVGES LRLLGNTFVA LSDLRCNLAC
360 370 380 390 400
APPRHLHVVR PMSHYTTPMV LQQAAIPIQI NVGTTVTMTG NGARPPPAPG
410 420 430 440 450
AEAATPGSAQ ATSLPPSSTT VDSSTEGAPP PGPAPPPASS HPRVIRISHQ
460 470 480 490 500
SVEPVVMMHM NIQDSGAQPG GVPSAPTGPL GPPGHGQTLG QQVPGFPTAP
510 520 530 540 550
TRVVIARPTP PQARPSHPGG PPVSGALQGA GLGTNTSLAQ MVSGLVGQLL
560 570 580 590 600
MQPVLVAQGT PGMAQAQAQA QAQAQAQAQA PAPAPAPAPA PATASASAGT
610 620 630 640 650
TNTATTAGPA PGGPAQPPPP QPSAADLQFS QLLGNLLGPA GPGAGGPGMA
660 670 680 690 700
SPTITVAMPG VPAFLQGMTD FLQASQTAPP PPPPPPPPPP APEQQSTPPP
710 720 730 740 750
GSPSGGTASP GGLGPESLPP EFFTSVVQGV LSSLLGSLGA RAGSSESIAA
760 770 780 790 800
FIQRLSGSSN IFEPGADGAL GFFGALLSLL CQNFSMVDVV MLLHGHFQPL
810 820 830 840 850
QRLQPQLRSF FHQHYLGGQE PTPSNIRMAT HTLITGLEEY VRESFSLVQV
860 870 880 890 900
QPGVDIIRTN LEFLQEQFNS IAAHVLHCTD SGFGARLLEL CNQGLFECLA
910 920 930 940 950
LNLHCLGGQQ MELAAVINGR IRRMSRGVNP SLVSWLTTMM GLRLQVVLEH
960 970 980 990 1000
MPVGPDAILR YVRRVGDPPQ TLPEEPMEVQ GAERTSPEPQ RENASPAPGT
1010 1020 1030 1040 1050
TAEEAMSRGP PPAPEGGSRD EQDGASADAE PWAAAVPPEW VPIIQQDIQS
1060 1070 1080 1090 1100
QRKVKPQPPL SDAYLSGMPA KRRKTMQGEG PQLLLSEAVS RAAKAAGARP
1110 1120 1130 1140 1150
LTSPESLSRD LEAPEVQESY RQQLRSDIQK RLQEDPNYSP QRFPNAHRAF
ADDP
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 528 | Missing in AAH26647 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 1012 | P → S in AAH26647 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF109719 Genomic DNA Translation: AAC82479.1 CR974444 Genomic DNA No translation available. BC026647 mRNA Translation: AAH26647.1 |
CCDSi | CCDS28688.1 |
RefSeqi | NP_476512.1, NM_057171.2 |
UniGenei | Mm.203962 |
Genome annotation databases
Ensembli | ENSMUST00000025250; ENSMUSP00000025250; ENSMUSG00000024392 |
GeneIDi | 224727 |
KEGGi | mmu:224727 |
UCSCi | uc008cgb.2 mouse |
Similar proteinsi
Entry informationi
Entry namei | BAG6_MOUSE | |
Accessioni | Q9Z1R2Primary (citable) accession number: Q9Z1R2 Secondary accession number(s): Q8SNA3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 27, 2005 |
Last sequence update: | May 1, 1999 | |
Last modified: | April 25, 2018 | |
This is version 136 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |