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Protein

Large proline-rich protein BAG6

Gene

BAG6

Organism
Ornithorhynchus anatinus (Duckbill platypus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

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 6By similarity
HLA-B-associated transcript 3By similarity
Gene namesi
Name:BAG6By similarity
Synonyms:BAT3By similarity
OrganismiOrnithorhynchus anatinus (Duckbill platypus)
Taxonomic identifieri9258 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaMonotremataOrnithorhynchidaeOrnithorhynchus
Proteomesi
  • UP000002279 Componenti: Unplaced

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

Keywords - Cellular componenti

Cytoplasm, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004037501 – 1088Large proline-rich protein BAG6Add BLAST1088

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei103PhosphoserineBy similarity1
Modified residuei354PhosphothreonineBy similarity1
Modified residuei976PhosphoserineBy similarity1
Modified residuei1073PhosphoserineBy similarity1

Post-translational modificationi

Ricin can induce the cleavage by the caspase CASP3.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1005 – 1006Cleavage; by CASP3By similarity2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PRIDEiA7X5R6.

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

Structurei

3D structure databases

ProteinModelPortaliA7X5R6.
SMRiA7X5R6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 99Ubiquitin-likePROSITE-ProRule annotationAdd BLAST76
Repeati243 – 2741By similarityAdd BLAST32
Repeati415 – 4422By similarityAdd BLAST28
Repeati571 – 5993By similarityAdd BLAST29
Repeati607 – 6404By similarityAdd BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni243 – 6404 X 29 AA approximate repeatsBy similarityAdd BLAST398
Regioni1027 – 1088Mediates interaction with UBL4A and GET4 and is sufficient for the delivery of client proteins to the endoplasmic reticulumBy similarityAdd BLAST62

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi197 – 277Pro-richPROSITE-ProRule annotationAdd BLAST81
Compositional biasi398 – 685Pro-richPROSITE-ProRule annotationAdd BLAST288

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

HOVERGENiHBG002193.
InParanoidiA7X5R6.

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.

Sequencei

Sequence statusi: Complete.

A7X5R6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPGGGGGGG GPGPGPDMEE PADLEVSVKT LDSQTRTFTV GAEMTVKEFK
60 70 80 90 100
EHIAAAVSIP PDKQRLIYQG RVLQDDKKLQ EYNVGGKVIH LVERAPPQTQ
110 120 130 140 150
GPSSGGASRA GSPSAPHAGA PPAGPRGPGA PVHDRNANSY VMVGTFNLPS
160 170 180 190 200
DGSAVDVHIN MEQAPIQSEP RVRLVMAQHM LRDIQALLAR LEPQPGQQGQ
210 220 230 240 250
QGQQQGQALL AESGPPRPGP PGQTDGETSP REPTETREPT ETREPEDGVA
260 270 280 290 300
ARGTGPAPGP APAPAPEGNA APNHPSPAEY AEVLQELQRV ESRLQPFLQR
310 320 330 340 350
YRAILGAAAT TDYNNNTEGR EEDQRVINLV GESLRLLGNT FVALSDLRCN
360 370 380 390 400
LSATAPRHLH VVRPMSHYTA PMVLQQAAIP IQINVGTTVT MTGSGARPGP
410 420 430 440 450
TDTTPTSGQT SSPTPSPTSG EPGPDGAPSG PAPPQAAGPP RLIRISHQSV
460 470 480 490 500
EPVVMMHMNI PDSGSQTGGT SSASTASTGL PGQGLGQQVS GFPAAPTRVV
510 520 530 540 550
IARPTPPQAR PPHPGGPPPA PGATIPVPGS NASLAQMVSG LVGQLLMQPV
560 570 580 590 600
LVAQGASGLG APQAPATASA SAGTTNTATT AGPAPGGPAQ PPPPPPPGPP
610 620 630 640 650
QAEVQFSQLL GSLLGPGVPG GPGTAGGATS VGSPTITVAM PGVPAFLQGM
660 670 680 690 700
TDFLQATQTA PPPPPPPPPP PAPEQAPAAA PPGSPPAGPG GAGGGPEALP
710 720 730 740 750
PEFFTSVVQG VLSSLLGSLG ARAGSGESIA GFIQRLSGSS NIFEPGADGA
760 770 780 790 800
LGFFGALLSV ICQNLSMVDV VMLLHGHSQP LQRLQPQLRG FFHQHYLGGR
810 820 830 840 850
EPTGPAIRRA THTLITGLEE YVRDSFASVQ VQPGVDITRT NLDFLQEQFN
860 870 880 890 900
GIAAHVLHCT DSSFGVRLLE LCNQGLFECL ALNLHCLGGQ QSALTNVING
910 920 930 940 950
RIRRLSGGVN PSLVSWLTTM MGLRLQVVLE HMPVGPDQVL RYVRRLGEPP
960 970 980 990 1000
QPPPEEPMDV QGAERAPPEP ERENASPAPG TTAEEAMSRG PPPAPEGPPP
1010 1020 1030 1040 1050
LEEQDGAAAA ESEPWAAAVP PEWVPIIRQD LQTQRKVKPQ PPLSDAYLSG
1060 1070 1080
MPAKRRKLRS DLQQRLRADP NYSPQHFPNA QRAFMDEP
Length:1,088
Mass (Da):112,586
Last modified:October 23, 2007 - v1
Checksum:i59144DCD0731671B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU030444 Genomic DNA. Translation: ABU86908.1.
RefSeqiNP_001229675.1. NM_001242746.1.

Genome annotation databases

GeneIDi100529065.
KEGGioaa:100529065.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU030444 Genomic DNA. Translation: ABU86908.1.
RefSeqiNP_001229675.1. NM_001242746.1.

3D structure databases

ProteinModelPortaliA7X5R6.
SMRiA7X5R6.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiA7X5R6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100529065.
KEGGioaa:100529065.

Organism-specific databases

CTDi7917.

Phylogenomic databases

HOVERGENiHBG002193.
InParanoidiA7X5R6.

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.
ProtoNetiSearch...

Entry informationi

Entry nameiBAG6_ORNAN
AccessioniPrimary (citable) accession number: A7X5R6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2011
Last sequence update: October 23, 2007
Last modified: June 7, 2017
This is version 49 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

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.