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Q9Z1R2 (BAG6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Large proline-rich protein BAG6
Alternative name(s):
BAG family molecular chaperone regulator 6
BCL2-associated athanogene 6
Short name=BAG-6
Short name=BAG6
HLA-B-associated transcript 3
Protein Scythe
Gene names
Name:Bag6
Synonyms:Bat3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1154 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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. 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 By similarity. 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. Ref.7 Ref.8 Ref.9

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). Ref.7 Ref.8 Ref.9

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 By similarity. Ref.7 Ref.8 Ref.9

Subunit structure

Component of the BAT3 complex, at least composed of BAG6/BAT3, UBL4A and GET3/TRC35. Interacts with CTCFL and p300/EP300. Interacts with ricin A chain By similarity. Interacts with AIFM1 and HSPA2. Ref.7 Ref.8

Subcellular location

Cytoplasmcytosol. Nucleus By similarity. Note: The C-terminal fragment generated by caspase-3 is cytoplasmic. Also found in extracellular vesicular exosomes in some tumor cells By similarity. Ref.7

Post-translational modification

Cleavage by caspase-3 releases a C-terminal peptide that plays a role in ricin-induced apoptosis By similarity.

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. Ref.4 Ref.5

Sequence similarities

Contains 1 ubiquitin-like domain.

Ontologies

Keywords
   Biological processApoptosis
Differentiation
Immunity
Spermatogenesis
Transport
   Cellular componentCytoplasm
Nucleus
   DomainRepeat
   Molecular functionChaperone
Chromatin regulator
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processantigen processing and presentation of peptide antigen via MHC class I

Traceable author statement Ref.9. Source: UniProtKB

brain development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

embryo development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

internal peptidyl-lysine acetylation

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from mutant phenotype Ref.7. Source: UniProtKB

kidney development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

lung development

Inferred from mutant phenotype Ref.4. Source: UniProtKB

negative regulation of apoptotic process

Inferred from genetic interaction PubMed 21460186. Source: MGI

negative regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.8. Source: UniProtKB

negative regulation of proteolysis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

protein stabilization

Inferred from mutant phenotype Ref.7Ref.8. Source: UniProtKB

regulation of apoptotic process

Inferred from mutant phenotype Ref.4. Source: UniProtKB

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

synaptonemal complex assembly

Inferred from mutant phenotype Ref.8. Source: UniProtKB

tail-anchored membrane protein insertion into ER membrane

Inferred from sequence or structural similarity. Source: UniProtKB

transport

Inferred from electronic annotation. Source: UniProtKB-KW

ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.9. Source: UniProtKB

   Cellular_componentBAT3 complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity PubMed 10390159. Source: MGI

cytosol

Inferred from direct assay Ref.7. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionHsp70 protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

polyubiquitin binding

Inferred from direct assay Ref.9. Source: UniProtKB

proteasome binding

Inferred from direct assay Ref.9. Source: UniProtKB

ribosome binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Camk2aP11798-23EBI-644645,EBI-400402
Tnfrsf11aO353054EBI-644645,EBI-647362

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11541154Large proline-rich protein BAG6
PRO_0000114898

Regions

Domain17 – 9276Ubiquitin-like
Repeat237 – 271351
Repeat416 – 444292
Repeat597 – 624283
Repeat630 – 658294
Region237 – 6584224 X 29 AA approximate repeats
Compositional bias196 – 27479Pro-rich
Compositional bias395 – 720326Pro-rich
Compositional bias564 – 61047Ala-rich

Sites

Site1023 – 10242Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue9861Phosphoserine By similarity
Modified residue9951Phosphoserine Ref.6
Modified residue11031Phosphoserine By similarity
Modified residue11391Phosphoserine By similarity

Experimental info

Sequence conflict5281Missing in AAH26647. Ref.3
Sequence conflict10121P → S in AAH26647. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9Z1R2 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 7F3FD14DF5AC1211

FASTA1,154121,037
        10         20         30         40         50         60 
MEPSDSASTA MEEPDSLEVL VKTLDSQTRT FIVGAQMNVK EFKEHIAASV SIPSEKQRLI 

        70         80         90        100        110        120 
YQGRVLQDDK KLQEYNVGGK VIHLVERAPP QTQLPSGASS GTGSASATHG GAPLPGTRGP 

       130        140        150        160        170        180 
GASVHDRNAN SYVMVGTFNL PSDGSAVDVH INMEQAPIQS EPRVRLVMAQ HMIRDIQTLL 

       190        200        210        220        230        240 
SRMECRGGTQ AQASQPPPQT PQTVASETVA LNSQTSEPVE SEAPPREPME SEEMEERPPT 

       250        260        270        280        290        300 
QTPELAPSGP APAGPAPAGP APAPETNAPN HPSPAEHVEV LQELQRLQRR LQPFLQRYCE 

       310        320        330        340        350        360 
VLGAAATTDY NNNHEGREED QRLINLVGES LRLLGNTFVA LSDLRCNLAC APPRHLHVVR 

       370        380        390        400        410        420 
PMSHYTTPMV LQQAAIPIQI NVGTTVTMTG NGARPPPAPG AEAATPGSAQ ATSLPPSSTT 

       430        440        450        460        470        480 
VDSSTEGAPP PGPAPPPASS HPRVIRISHQ SVEPVVMMHM NIQDSGAQPG GVPSAPTGPL 

       490        500        510        520        530        540 
GPPGHGQTLG QQVPGFPTAP TRVVIARPTP PQARPSHPGG PPVSGALQGA GLGTNTSLAQ 

       550        560        570        580        590        600 
MVSGLVGQLL MQPVLVAQGT PGMAQAQAQA QAQAQAQAQA PAPAPAPAPA PATASASAGT 

       610        620        630        640        650        660 
TNTATTAGPA PGGPAQPPPP QPSAADLQFS QLLGNLLGPA GPGAGGPGMA SPTITVAMPG 

       670        680        690        700        710        720 
VPAFLQGMTD FLQASQTAPP PPPPPPPPPP APEQQSTPPP GSPSGGTASP GGLGPESLPP 

       730        740        750        760        770        780 
EFFTSVVQGV LSSLLGSLGA RAGSSESIAA FIQRLSGSSN IFEPGADGAL GFFGALLSLL 

       790        800        810        820        830        840 
CQNFSMVDVV MLLHGHFQPL QRLQPQLRSF FHQHYLGGQE PTPSNIRMAT HTLITGLEEY 

       850        860        870        880        890        900 
VRESFSLVQV QPGVDIIRTN LEFLQEQFNS IAAHVLHCTD SGFGARLLEL CNQGLFECLA 

       910        920        930        940        950        960 
LNLHCLGGQQ MELAAVINGR IRRMSRGVNP SLVSWLTTMM GLRLQVVLEH MPVGPDAILR 

       970        980        990       1000       1010       1020 
YVRRVGDPPQ TLPEEPMEVQ GAERTSPEPQ RENASPAPGT TAEEAMSRGP PPAPEGGSRD 

      1030       1040       1050       1060       1070       1080 
EQDGASADAE PWAAAVPPEW VPIIQQDIQS QRKVKPQPPL SDAYLSGMPA KRRKTMQGEG 

      1090       1100       1110       1120       1130       1140 
PQLLLSEAVS RAAKAAGARP LTSPESLSRD LEAPEVQESY RQQLRSDIQK RLQEDPNYSP 

      1150 
QRFPNAHRAF ADDP 

« Hide

References

« Hide 'large scale' references
[1]"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse."
Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.
Genome Res. 13:2621-2636(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: 129.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 318-1154.
Strain: FVB/N.
Tissue: Colon.
[4]"The reaper-binding protein scythe modulates apoptosis and proliferation during mammalian development."
Desmots F., Russell H.R., Lee Y., Boyd K., McKinnon P.J.
Mol. Cell. Biol. 25:10329-10337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53."
Sasaki T., Gan E.C., Wakeham A., Kornbluth S., Mak T.W., Okada H.
Genes Dev. 21:848-861(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-995, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Scythe regulates apoptosis-inducing factor stability during endoplasmic reticulum stress-induced apoptosis."
Desmots F., Russell H.R., Michel D., McKinnon P.J.
J. Biol. Chem. 283:3264-3271(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AIFM1, SUBCELLULAR LOCATION.
[8]"Bat3 deficiency accelerates the degradation of Hsp70-2/HspA2 during spermatogenesis."
Sasaki T., Marcon E., McQuire T., Arai Y., Moens P.B., Okada H.
J. Cell Biol. 182:449-458(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HSPA2.
[9]"BAG-6 is essential for selective elimination of defective proteasomal substrates."
Minami R., Hayakawa A., Kagawa H., Yanagi Y., Yokosawa H., Kawahara H.
J. Cell Biol. 190:637-650(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF109719 Genomic DNA. Translation: AAC82479.1.
CR974444 Genomic DNA. No translation available.
BC026647 mRNA. Translation: AAH26647.1.
RefSeqNP_476512.1. NM_057171.2.
UniGeneMm.203962.

3D structure databases

ProteinModelPortalQ9Z1R2.
SMRQ9Z1R2. Positions 13-87.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid230309. 3 interactions.
IntActQ9Z1R2. 6 interactions.
MINTMINT-1563095.

PTM databases

PhosphoSiteQ9Z1R2.

Proteomic databases

PaxDbQ9Z1R2.
PRIDEQ9Z1R2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025250; ENSMUSP00000025250; ENSMUSG00000024392.
GeneID224727.
KEGGmmu:224727.
UCSCuc008cgb.2. mouse.

Organism-specific databases

CTD7917.
MGIMGI:1919439. Bag6.

Phylogenomic databases

eggNOGNOG297129.
GeneTreeENSGT00390000016199.
HOVERGENHBG002193.
InParanoidQ9Z1R2.
OMAQEPTPGN.
PhylomeDBQ9Z1R2.
TreeFamTF328437.

Gene expression databases

ArrayExpressQ9Z1R2.
BgeeQ9Z1R2.
CleanExMM_BAT3.
GenevestigatorQ9Z1R2.

Family and domain databases

InterProIPR021925. DUF3538.
IPR000626. Ubiquitin-like.
IPR019954. Ubiquitin_CS.
[Graphical view]
PfamPF12057. DUF3538. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]
SMARTSM00213. UBQ. 1 hit.
[Graphical view]
PROSITEPS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio377324.
PROQ9Z1R2.
SOURCESearch...

Entry information

Entry nameBAG6_MOUSE
AccessionPrimary (citable) accession number: Q9Z1R2
Secondary accession number(s): Q8SNA3
Entry history
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

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