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Q9Z1R2

- BAG6_MOUSE

UniProt

Q9Z1R2 - BAG6_MOUSE

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Protein

Large proline-rich protein BAG6

Gene
Bag6, Bat3
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.3 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).3 Publications
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.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei1023 – 10242Cleavage; by caspase-3 By similarity

GO - Molecular functioni

  1. Hsp70 protein binding Source: UniProtKB
  2. polyubiquitin binding Source: UniProtKB
  3. proteasome binding Source: UniProtKB
  4. protein binding Source: UniProtKB
  5. ribosome binding Source: UniProtKB

GO - Biological processi

  1. antigen processing and presentation of peptide antigen via MHC class I Source: UniProtKB
  2. brain development Source: UniProtKB
  3. cell differentiation Source: UniProtKB-KW
  4. chromatin modification Source: UniProtKB-KW
  5. embryo development Source: UniProtKB
  6. internal peptidyl-lysine acetylation Source: UniProtKB
  7. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
  8. intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
  9. kidney development Source: UniProtKB
  10. lung development Source: UniProtKB
  11. negative regulation of apoptotic process Source: MGI
  12. negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  13. negative regulation of proteolysis Source: UniProtKB
  14. protein stabilization Source: UniProtKB
  15. regulation of apoptotic process Source: UniProtKB
  16. regulation of cell proliferation Source: Ensembl
  17. spermatogenesis Source: UniProtKB
  18. synaptonemal complex assembly Source: UniProtKB
  19. tail-anchored membrane protein insertion into ER membrane Source: UniProtKB
  20. transport Source: UniProtKB-KW
  21. ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Chromatin regulator

Keywords - Biological processi

Apoptosis, Differentiation, Immunity, Spermatogenesis, Transport

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Bag6
Synonyms:Bat3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 17

Organism-specific databases

MGIiMGI:1919439. Bag6.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. BAT3 complex Source: UniProtKB
  2. cytoplasm Source: MGI
  3. cytosol Source: UniProtKB
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11541154Large proline-rich protein BAG6PRO_0000114898Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine By similarity
Modified residuei986 – 9861Phosphoserine By similarity
Modified residuei995 – 9951Phosphoserine1 Publication
Modified residuei1103 – 11031Phosphoserine By similarity
Modified residuei1139 – 11391Phosphoserine By similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ9Z1R2.
PaxDbiQ9Z1R2.
PRIDEiQ9Z1R2.

PTM databases

PhosphoSiteiQ9Z1R2.

Expressioni

Gene expression databases

ArrayExpressiQ9Z1R2.
BgeeiQ9Z1R2.
CleanExiMM_BAT3.
GenevestigatoriQ9Z1R2.

Interactioni

Subunit structurei

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 HSPA2.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Camk2aP11798-23EBI-644645,EBI-400402
Tnfrsf11aO353054EBI-644645,EBI-647362

Protein-protein interaction databases

BioGridi230309. 4 interactions.
IntActiQ9Z1R2. 6 interactions.
MINTiMINT-1563095.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1R2.
SMRiQ9Z1R2. Positions 13-87.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini17 – 9276Ubiquitin-likeAdd
BLAST
Repeati237 – 271351Add
BLAST
Repeati416 – 444292Add
BLAST
Repeati597 – 624283Add
BLAST
Repeati630 – 658294Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni237 – 6584224 X 29 AA approximate repeatsAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi196 – 27479Pro-richAdd
BLAST
Compositional biasi395 – 720326Pro-richAdd
BLAST
Compositional biasi564 – 61047Ala-richAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG297129.
GeneTreeiENSGT00390000016199.
HOVERGENiHBG002193.
InParanoidiQ9Z1R2.
OMAiQEPTPGN.
PhylomeDBiQ9Z1R2.
TreeFamiTF328437.

Family and domain databases

InterProiIPR021925. DUF3538.
IPR000626. Ubiquitin-like.
IPR029071. Ubiquitin-rel_dom.
IPR019954. Ubiquitin_CS.
[Graphical view]
PfamiPF12057. DUF3538. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view]
SMARTiSM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z1R2-1 [UniParc]FASTAAdd to Basket

« Hide

MEPSDSASTA MEEPDSLEVL VKTLDSQTRT FIVGAQMNVK EFKEHIAASV     50
SIPSEKQRLI YQGRVLQDDK KLQEYNVGGK VIHLVERAPP QTQLPSGASS 100
GTGSASATHG GAPLPGTRGP GASVHDRNAN SYVMVGTFNL PSDGSAVDVH 150
INMEQAPIQS EPRVRLVMAQ HMIRDIQTLL SRMECRGGTQ AQASQPPPQT 200
PQTVASETVA LNSQTSEPVE SEAPPREPME SEEMEERPPT QTPELAPSGP 250
APAGPAPAGP APAPETNAPN HPSPAEHVEV LQELQRLQRR LQPFLQRYCE 300
VLGAAATTDY NNNHEGREED QRLINLVGES LRLLGNTFVA LSDLRCNLAC 350
APPRHLHVVR PMSHYTTPMV LQQAAIPIQI NVGTTVTMTG NGARPPPAPG 400
AEAATPGSAQ ATSLPPSSTT VDSSTEGAPP PGPAPPPASS HPRVIRISHQ 450
SVEPVVMMHM NIQDSGAQPG GVPSAPTGPL GPPGHGQTLG QQVPGFPTAP 500
TRVVIARPTP PQARPSHPGG PPVSGALQGA GLGTNTSLAQ MVSGLVGQLL 550
MQPVLVAQGT PGMAQAQAQA QAQAQAQAQA PAPAPAPAPA PATASASAGT 600
TNTATTAGPA PGGPAQPPPP QPSAADLQFS QLLGNLLGPA GPGAGGPGMA 650
SPTITVAMPG VPAFLQGMTD FLQASQTAPP PPPPPPPPPP APEQQSTPPP 700
GSPSGGTASP GGLGPESLPP EFFTSVVQGV LSSLLGSLGA RAGSSESIAA 750
FIQRLSGSSN IFEPGADGAL GFFGALLSLL CQNFSMVDVV MLLHGHFQPL 800
QRLQPQLRSF FHQHYLGGQE PTPSNIRMAT HTLITGLEEY VRESFSLVQV 850
QPGVDIIRTN LEFLQEQFNS IAAHVLHCTD SGFGARLLEL CNQGLFECLA 900
LNLHCLGGQQ MELAAVINGR IRRMSRGVNP SLVSWLTTMM GLRLQVVLEH 950
MPVGPDAILR YVRRVGDPPQ TLPEEPMEVQ GAERTSPEPQ RENASPAPGT 1000
TAEEAMSRGP PPAPEGGSRD EQDGASADAE PWAAAVPPEW VPIIQQDIQS 1050
QRKVKPQPPL SDAYLSGMPA KRRKTMQGEG PQLLLSEAVS RAAKAAGARP 1100
LTSPESLSRD LEAPEVQESY RQQLRSDIQK RLQEDPNYSP QRFPNAHRAF 1150
ADDP 1154
Length:1,154
Mass (Da):121,037
Last modified:May 1, 1999 - v1
Checksum:i7F3FD14DF5AC1211
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti528 – 5281Missing in AAH26647. 1 Publication
Sequence conflicti1012 – 10121P → S in AAH26647. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

3D structure databases

ProteinModelPortali Q9Z1R2.
SMRi Q9Z1R2. Positions 13-87.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 230309. 4 interactions.
IntActi Q9Z1R2. 6 interactions.
MINTi MINT-1563095.

PTM databases

PhosphoSitei Q9Z1R2.

Proteomic databases

MaxQBi Q9Z1R2.
PaxDbi Q9Z1R2.
PRIDEi Q9Z1R2.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000025250 ; ENSMUSP00000025250 ; ENSMUSG00000024392 .
GeneIDi 224727.
KEGGi mmu:224727.
UCSCi uc008cgb.2. mouse.

Organism-specific databases

CTDi 7917.
MGIi MGI:1919439. Bag6.

Phylogenomic databases

eggNOGi NOG297129.
GeneTreei ENSGT00390000016199.
HOVERGENi HBG002193.
InParanoidi Q9Z1R2.
OMAi QEPTPGN.
PhylomeDBi Q9Z1R2.
TreeFami TF328437.

Miscellaneous databases

NextBioi 377324.
PROi Q9Z1R2.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9Z1R2.
Bgeei Q9Z1R2.
CleanExi MM_BAT3.
Genevestigatori Q9Z1R2.

Family and domain databases

InterProi IPR021925. DUF3538.
IPR000626. Ubiquitin-like.
IPR029071. Ubiquitin-rel_dom.
IPR019954. Ubiquitin_CS.
[Graphical view ]
Pfami PF12057. DUF3538. 1 hit.
PF00240. ubiquitin. 1 hit.
[Graphical view ]
SMARTi SM00213. UBQ. 1 hit.
[Graphical view ]
SUPFAMi SSF54236. SSF54236. 1 hit.
PROSITEi PS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiBAG6_MOUSE
AccessioniPrimary (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: July 9, 2014
This is version 101 of the entry and version 1 of the sequence. [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
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi