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Protein

Large proline-rich protein BAG6

Gene

Bag6

Organism
Rattus norvegicus (Rat)
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. 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. 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. 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. 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 inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis. Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1.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).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

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):
BCL2-associated athanogene 6Imported
HLA-B-associated transcript 31 Publication
Gene namesi
Name:Bag6Imported
Synonyms:Bat31 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi71064. Bag6.

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Nucleus By similarity
  • Secretedexosome By similarity

  • Note: Normally localized in cytosol and nucleus, it can also be released extracellularly, in exosomes, by tumor and myeloid dendritic cells.By similarity

GO - Cellular componenti

  • BAT3 complex Source: UniProtKB
  • cytoplasm Source: RGD
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB-SubCell
  • membrane Source: Ensembl
  • nucleoplasm Source: Ensembl
  • nucleus Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001148991 – 1146Large proline-rich protein BAG6Add BLAST1146

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei96PhosphoserineBy similarity1
Modified residuei117PhosphothreonineBy similarity1
Modified residuei978PhosphoserineBy similarity1
Modified residuei987PhosphoserineCombined sources1
Modified residuei1067PhosphothreonineBy similarity1
Modified residuei1095PhosphoserineCombined sources1
Modified residuei1131PhosphoserineBy 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
Sitei1015 – 1016Cleavage; by CASP3By similarity2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ6MG49.
PRIDEiQ6MG49.

PTM databases

iPTMnetiQ6MG49.
PhosphoSitePlusiQ6MG49.

Expressioni

Gene expression databases

BgeeiENSRNOG00000000851.
ExpressionAtlasiQ6MG49. baseline and differential.
GenevisibleiQ6MG49. RN.

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. Interacts with HSPA2 (By similarity). 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 similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi250197. 2 interactors.
IntActiQ6MG49. 2 interactors.
MINTiMINT-4566953.
STRINGi10116.ENSRNOP00000057557.

Structurei

3D structure databases

ProteinModelPortaliQ6MG49.
SMRiQ6MG49.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 92Ubiquitin-likePROSITE-ProRule annotationAdd BLAST76
Repeati236 – 2651By similarityAdd BLAST30
Repeati410 – 4382By similarityAdd BLAST29
Repeati589 – 6163By similarityAdd BLAST28
Repeati622 – 6504By similarityAdd BLAST29

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni236 – 6504 X 29 AA approximate repeatsBy similarityAdd BLAST415
Regioni1036 – 1146Mediates 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 – 268Pro-richPROSITE-ProRule annotationAdd BLAST73
Compositional biasi389 – 711Pro-richPROSITE-ProRule annotationAdd BLAST323

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.
HOGENOMiHOG000095177.
HOVERGENiHBG002193.
InParanoidiQ6MG49.
OMAiLPVHVMT.
OrthoDBiEOG091G0XSR.
PhylomeDBiQ6MG49.
TreeFamiTF328437.

Family and domain databases

InterProiView protein in InterPro
IPR021925. DUF3538.
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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6MG49-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPSDSTSTA MEEPDSLEVL VKTLDSQTRT FIVGAQMNVK EFKEHIAASV
60 70 80 90 100
SIPSEKQRLI YQGRVLQDDK KLQDYNVGGK VIHLVERAPP QTQLPSGASS
110 120 130 140 150
GTGSASATHG GGPLPGTRGP GASGHDRNAN SYVMVGTFNL PSDGSAVDVH
160 170 180 190 200
INMEQAPIQS EPRVRLVMAQ HMIRDIQTLL SRMECRGGTQ AQASQPPPQT
210 220 230 240 250
PTVASETVAL NSQTSEPVES EAPPREPMES EEMEERPPTQ TPELPPSGPA
260 270 280 290 300
PAGPAPAPET NAPNHPSPAE HVEVLQELQR LQRRLQPFLQ RYCEVLGAAA
310 320 330 340 350
TTDYNNNHEG REEDQRLINL VGESLRLLGN TFVALSDLRC NLACAPPRHL
360 370 380 390 400
HVVRPMSHYT TPMVLQQAAI PIQINVGTTV TMTGNGARPP PAPGAEAASP
410 420 430 440 450
GSGQASSLPP SSATVDSSTE GAPPPGPAPP PATSHPRVIR ISHQSVEPVV
460 470 480 490 500
MMHMNIQDSG AQPGGVPSAP TGPLGPPGHG QSLGQQVPGF PTAPTRVVIA
510 520 530 540 550
RPTPPQARPS HPGGPPVSGA LQGAGLGTNT SLAQMVSGLV GQLLMQPVLV
560 570 580 590 600
AQGTPGMAPA SASAPATAQA QAPAPAPAPA PAPATASASA GTTNTATTAG
610 620 630 640 650
PAPGGPAQPP PPQPSAADLQ FSQLLGNLLG PAGPGAGGPS LASPTITVAV
660 670 680 690 700
PGVPAFLQGM TEFLQASQAA PPPPPPPPPP PPAPEQQTTP PPGSPSGGTA
710 720 730 740 750
SPGGLGPESL PPEFFTSVVQ GVLSSLLGSL GARAGSSESI AAFIQRLSGS
760 770 780 790 800
SNIFEPGADG ALGFFGALLS LLCQNFSMVD VVMLLHGHFQ PLQRLQPQLR
810 820 830 840 850
SFFHQHYLGG QEPTSSNIRM ATHTLITGLE EYVRESFSLV QVQPGVDIIR
860 870 880 890 900
TNLEFLQEQF NSIAAHVLHC TDSGFGARLL ELCNQGLFEC LALNLHCLGG
910 920 930 940 950
QQMELAAVIN GRIRRMSRGV NPSLVSWLTT MMGLRLQVVL EHMPVGPDAI
960 970 980 990 1000
LRYVRRIGDP PQALPEEPME VQGAERTSPE PQREDASPAP GTTAEEAMSR
1010 1020 1030 1040 1050
GPPPAPEGGS RDEQDGASAD AEPWAAAVPP EWVPIIQQDI QSQRKVKPQP
1060 1070 1080 1090 1100
PLSDAYLSGM PAKRRKTMQG EGPQLLLSEA VSRAAKAAGA RPLTSPESLS
1110 1120 1130 1140
RDLEAPEVQE SYRQQLRSDI QKRLQEDPNY SPQRFPNAHR AFADDP
Length:1,146
Mass (Da):120,012
Last modified:January 11, 2011 - v2
Checksum:i9CAA4CD9C04F3C29
GO
Isoform 2 (identifier: Q6MG49-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     522-522: Missing.
     1067-1115: Missing.

Show »
Length:1,096
Mass (Da):114,647
Checksum:iE372D70E024D8F15
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4S → N in BAA76607 (PubMed:10390159).Curated1
Sequence conflicti11M → V in BAA76607 (PubMed:10390159).Curated1
Sequence conflicti47A → R in BAA76607 (PubMed:10390159).Curated1
Sequence conflicti74D → E in BAA76607 (PubMed:10390159).Curated1
Sequence conflicti93Q → H in BAA76607 (PubMed:10390159).Curated1
Sequence conflicti114L → C in BAA76607 (PubMed:10390159).Curated1
Sequence conflicti189T → N in BAA76607 (PubMed:10390159).Curated1
Sequence conflicti264 – 265NH → TQ in BAA76607 (PubMed:10390159).Curated2
Sequence conflicti567T → TAQ in BAA76607 (PubMed:10390159).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_040420522Missing in isoform 2. 1 Publication1
Alternative sequenceiVSP_0404211067 – 1115Missing in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB018791 mRNA. Translation: BAA76607.1.
BX883045 Genomic DNA. Translation: CAE83997.1.
CH474121 Genomic DNA. Translation: EDL83534.1.
BC100141 mRNA. Translation: AAI00142.1.
RefSeqiNP_001029140.1. NM_001033968.1. [Q6MG49-1]
NP_446061.2. NM_053609.2. [Q6MG49-2]
UniGeneiRn.203343.

Genome annotation databases

EnsembliENSRNOT00000001129; ENSRNOP00000001129; ENSRNOG00000000851. [Q6MG49-2]
ENSRNOT00000060832; ENSRNOP00000057557; ENSRNOG00000000851. [Q6MG49-1]
GeneIDi94342.
KEGGirno:94342.
UCSCiRGD:71064. rat. [Q6MG49-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiBAG6_RAT
AccessioniPrimary (citable) accession number: Q6MG49
Secondary accession number(s): Q498N5, Q9WTN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: January 11, 2011
Last modified: June 7, 2017
This is version 105 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome