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Protein

Large proline-rich protein BAG6

Gene

Bag6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

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
  • covalent chromatin modification 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
  • transport Source: UniProtKB-KW
  • ubiquitin-dependent ERAD pathway Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Molecular functionChaperone, Chromatin regulator
Biological processApoptosis, Differentiation, Immunity, Spermatogenesis, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Large proline-rich protein BAG6Curated
Alternative 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
Name:Bag6Imported
Synonyms:Bat31 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1919439. Bag6.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus, Secreted

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 keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001148981 – 1154Large proline-rich protein BAG6Add BLAST1154

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei96PhosphoserineBy similarity1
Modified residuei117PhosphothreonineBy similarity1
Modified residuei986PhosphoserineBy similarity1
Modified residuei995PhosphoserineCombined sources1
Modified residuei1075PhosphothreonineBy similarity1
Modified residuei1103PhosphoserineBy similarity1
Modified residuei1139PhosphoserineBy similarity1

Post-translational modificationi

Ricin can induce a cleavage by the caspase CASP3. The released C-terminal peptide induces apoptosis.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1023 – 1024Cleavage; by CASP3By similarity2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Z1R2.
MaxQBiQ9Z1R2.
PaxDbiQ9Z1R2.
PRIDEiQ9Z1R2.

PTM databases

iPTMnetiQ9Z1R2.
PhosphoSitePlusiQ9Z1R2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000024392.
CleanExiMM_BAT3.
ExpressionAtlasiQ9Z1R2. baseline and differential.
GenevisibleiQ9Z1R2. 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

Show more details

GO - Molecular functioni

  • Hsp70 protein binding Source: UniProtKB
  • misfolded protein binding Source: MGI
  • polyubiquitin modification-dependent protein binding Source: UniProtKB
  • proteasome binding Source: UniProtKB
  • receptor binding Source: MGI
  • ubiquitin protein ligase binding Source: MGI
  • ubiquitin-specific protease binding Source: MGI

Protein-protein interaction databases

BioGridi230309. 6 interactors.
DIPiDIP-49391N.
IntActiQ9Z1R2. 7 interactors.
MINTiMINT-1563095.
STRINGi10090.ENSMUSP00000025250.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1R2.
SMRiQ9Z1R2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 92Ubiquitin-likePROSITE-ProRule annotationAdd BLAST76
Repeati237 – 2711By similarityAdd BLAST35
Repeati416 – 4442By similarityAdd BLAST29
Repeati597 – 6243By similarityAdd BLAST28
Repeati630 – 6584By similarityAdd BLAST29

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni237 – 6584 X 29 AA approximate repeatsBy similarityAdd BLAST422
Regioni1044 – 1154Mediates interaction with UBL4A and GET4 and is sufficient for the delivery of client proteins to the endoplasmic reticulumBy similarityAdd BLAST111

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi196 – 274Pro-richPROSITE-ProRule annotationAdd BLAST79
Compositional biasi395 – 720Pro-richPROSITE-ProRule annotationAdd BLAST326
Compositional biasi564 – 610Ala-richAdd BLAST47

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

Repeat

Phylogenomic databases

eggNOGiKOG4248. Eukaryota.
ENOG410XS9P. LUCA.
GeneTreeiENSGT00390000016199.
HOVERGENiHBG002193.
InParanoidiQ9Z1R2.
OMAiLPVHVMT.
OrthoDBiEOG091G0XSR.
PhylomeDBiQ9Z1R2.
TreeFamiTF328437.

Family and domain databases

InterProiView protein in InterPro
IPR021925. BAG6.
IPR029071. Ubiquitin-rel_dom.
IPR019954. Ubiquitin_CS.
IPR000626. Ubiquitin_dom.
PfamiView protein in Pfam
PF12057. DUF3538. 1 hit.
PF00240. ubiquitin. 1 hit.
SMARTiView protein in SMART
SM00213. UBQ. 1 hit.
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiView protein in PROSITE
PS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9Z1R2-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:1,154
Mass (Da):121,037
Last modified:May 1, 1999 - v1
Checksum:i7F3FD14DF5AC1211
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti528Missing in AAH26647 (PubMed:15489334).Curated1
Sequence conflicti1012P → S in AAH26647 (PubMed:15489334).Curated1

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.
CCDSiCCDS28688.1.
RefSeqiNP_476512.1. NM_057171.2.
UniGeneiMm.203962.

Genome annotation databases

EnsembliENSMUST00000025250; ENSMUSP00000025250; ENSMUSG00000024392.
GeneIDi224727.
KEGGimmu:224727.
UCSCiuc008cgb.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiBAG6_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1R2
Secondary accession number(s): Q8SNA3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: May 1, 1999
Last modified: September 27, 2017
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot