Q9Z1R2 (BAG6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Bag6
Synonyms:	Bat3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1154 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Cytoplasm › cytosol. 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 process	Apoptosis Differentiation Immunity Spermatogenesis Transport
Cellular component	Cytoplasm Nucleus
Domain	Repeat
Molecular function	Chaperone Chromatin regulator
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen 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_component	BAT3 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_function	Hsp70 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
Camk2a	P11798-2	3	EBI-644645,EBI-400402
Tnfrsf11a	O35305	4	EBI-644645,EBI-647362

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1154	1154	Large proline-rich protein BAG6		PRO_0000114898
Regions
	Domain	17 – 92	76	Ubiquitin-like
	Repeat	237 – 271	35	1
	Repeat	416 – 444	29	2
	Repeat	597 – 624	28	3
	Repeat	630 – 658	29	4
	Region	237 – 658	422	4 X 29 AA approximate repeats
	Compositional bias	196 – 274	79	Pro-rich
	Compositional bias	395 – 720	326	Pro-rich
	Compositional bias	564 – 610	47	Ala-rich
Sites
	Site	1023 – 1024	2	Cleavage; by caspase-3 By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	986	1	Phosphoserine By similarity
	Modified residue	995	1	Phosphoserine Ref.6
	Modified residue	1103	1	Phosphoserine By similarity
	Modified residue	1139	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	528	1	Missing in AAH26647. Ref.3
	Sequence conflict	1012	1	P → S in AAH26647. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9Z1R2 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 7F3FD14DF5AC1211	FASTA	1,154	121,037
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
RefSeq	NP_476512.1. NM_057171.2.
UniGene	Mm.203962.
3D structure databases
ProteinModelPortal	Q9Z1R2.
SMR	Q9Z1R2. Positions 13-87.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	230309. 3 interactions.
IntAct	Q9Z1R2. 6 interactions.
MINT	MINT-1563095.
PTM databases
PhosphoSite	Q9Z1R2.
Proteomic databases
PaxDb	Q9Z1R2.
PRIDE	Q9Z1R2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000025250; ENSMUSP00000025250; ENSMUSG00000024392.
GeneID	224727.
KEGG	mmu:224727.
UCSC	uc008cgb.2. mouse.
Organism-specific databases
CTD	7917.
MGI	MGI:1919439. Bag6.
Phylogenomic databases
eggNOG	NOG297129.
GeneTree	ENSGT00390000016199.
HOVERGEN	HBG002193.
InParanoid	Q9Z1R2.
OMA	QEPTPGN.
PhylomeDB	Q9Z1R2.
TreeFam	TF328437.
Gene expression databases
ArrayExpress	Q9Z1R2.
Bgee	Q9Z1R2.
CleanEx	MM_BAT3.
Genevestigator	Q9Z1R2.
Family and domain databases
InterPro	IPR021925. DUF3538. IPR000626. Ubiquitin-like. IPR019954. Ubiquitin_CS. [Graphical view]
Pfam	PF12057. DUF3538. 1 hit. PF00240. ubiquitin. 1 hit. [Graphical view]
SMART	SM00213. UBQ. 1 hit. [Graphical view]
PROSITE	PS00299. UBIQUITIN_1. 1 hit. PS50053. UBIQUITIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	377324.
PRO	Q9Z1R2.
SOURCE	Search...

Entry information

Entry name

BAG6_MOUSE

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program