Entry euk:BAG6_RAT

ID   BAG6_RAT                Reviewed;        1146 AA.
AC   Q6MG49; Q498N5; Q9WTN8;
DT   27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 2.
DT   10-MAY-2017, entry version 104.
DE   RecName: Full=Large proline-rich protein BAG6 {ECO:0000305};
DE   AltName: Full=BCL2-associated athanogene 6 {ECO:0000312|RGD:71064};
DE   AltName: Full=HLA-B-associated transcript 3 {ECO:0000303|PubMed:10390159};
GN   Name=Bag6 {ECO:0000312|RGD:71064};
GN   Synonyms=Bat3 {ECO:0000303|PubMed:10390159};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX   PubMed=10390159; DOI=10.1089/104454999315222;
RA   Ozaki T., Hanaoka E., Naka M., Nakagawara A., Sakiyama S.;
RT   "Cloning and characterization of rat BAT3 cDNA.";
RL   DNA Cell Biol. 18:503-512(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15060004; DOI=10.1101/gr.1987704;
RA   Hurt P., Walter L., Sudbrak R., Klages S., Mueller I., Shiina T.,
RA   Inoko H., Lehrach H., Guenther E., Reinhardt R., Himmelbauer H.;
RT   "The genomic sequence and comparative analysis of the rat major
RT   histocompatibility complex.";
RL   Genome Res. 14:631-639(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-987 AND SER-1095, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
RA   Lundby C., Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14
RT   different rat organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: ATP-independent molecular chaperone preventing the
CC       aggregation of misfolded and hydrophobic patches-containing
CC       proteins. Functions as part of a cytosolic protein quality control
CC       complex, the BAG6/BAT3 complex, which maintains these client
CC       proteins in a soluble state and participates to their proper
CC       delivery to the endoplasmic reticulum or alternatively can promote
CC       their sorting to the proteasome where they undergo degradation.
CC       The BAG6/BAT3 complex is involved in the post-translational
CC       delivery of tail-anchored/type II transmembrane proteins to the
CC       endoplasmic reticulum membrane. Recruited to ribosomes, it
CC       interacts with the transmembrane region of newly synthesized tail-
CC       anchored proteins and together with SGTA and ASNA1 mediates their
CC       delivery to the endoplasmic reticulum. Client proteins that cannot
CC       be properly delivered to the endoplasmic reticulum are
CC       ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated
CC       with BAG6 and are sorted to the proteasome. SGTA which prevents
CC       the recruitment of RNF126 to BAG6 may negatively regulate the
CC       ubiquitination and the proteasomal degradation of client proteins.
CC       Similarly, the BAG6/BAT3 complex also functions as a sorting
CC       platform for proteins of the secretory pathway that are
CC       mislocalized to the cytosol either delivering them to the
CC       proteasome for degradation or to the endoplasmic reticulum. The
CC       BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-
CC       associated degradation (ERAD), a quality control mechanism that
CC       eliminates unwanted proteins of the endoplasmic reticulum through
CC       their retrotranslocation to the cytosol and their targeting to the
CC       proteasome. It maintains these retrotranslocated proteins in an
CC       unfolded yet soluble state condition in the cytosol to ensure
CC       their proper delivery to the proteasome. BAG6 is also required for
CC       selective ubiquitin-mediated degradation of defective nascent
CC       chain polypeptides by the proteasome. In this context, it may
CC       participate to the production of antigenic peptides and play a
CC       role in antigen presentation in immune response. BAG6 is also
CC       involved in endoplasmic reticulum stress-induced pre-emptive
CC       quality control, a mechanism that selectively attenuates the
CC       translocation of newly synthesized proteins into the endoplasmic
CC       reticulum and reroutes them to the cytosol for proteasomal
CC       degradation. BAG6 may ensure the proper degradation of these
CC       proteins and thereby protects the endoplasmic reticulum from
CC       protein overload upon stress. By inhibiting the polyubiquitination
CC       and subsequent proteasomal degradation of HSPA2 it may also play a
CC       role in the assembly of the synaptonemal complex during
CC       spermatogenesis. Also positively regulates apoptosis by
CC       interacting with and stabilizing the proapoptotic factor AIFM1.
CC       {ECO:0000250|UniProtKB:P46379}.
CC   -!- FUNCTION: Involved in DNA damage-induced apoptosis: following DNA
CC       damage, accumulates in the nucleus and forms a complex with
CC       p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation
CC       leading to increase p53/TP53 transcriptional activity. When
CC       nuclear, may also act as a component of some chromatin regulator
CC       complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2).
CC       {ECO:0000250|UniProtKB:P46379}.
CC   -!- FUNCTION: Released extracellularly via exosomes, it is a ligand of
CC       the natural killer/NK cells receptor NCR3 and stimulates NK cells
CC       cytotoxicity. It may thereby trigger NK cells cytotoxicity against
CC       neighboring tumor cells and immature myeloid dendritic cells (DC).
CC       {ECO:0000250|UniProtKB:P46379}.
CC   -!- FUNCTION: May mediate ricin-induced apoptosis.
CC       {ECO:0000250|UniProtKB:P46379}.
CC   -!- SUBUNIT: Component of the BAG6/BAT3 complex, also named BAT3
CC       complex, at least composed of BAG6, UBL4A and GET4/TRC35.
CC       Interacts with GET4; the interaction is direct and localizes BAG6
CC       in the cytosol (By similarity). Interacts with AIFM1. Interacts
CC       with HSPA2 (By similarity). Interacts with CTCFL. Interacts with
CC       p300/EP300. Interacts (via ubiquitin-like domain) with RNF126;
CC       required for BAG6-dependent ubiquitination of proteins
CC       mislocalized to the cytosol. Interacts (via ubiquitin-like domain)
CC       with SGTA; SGTA competes with RNF126 by binding the same region of
CC       BAG6, thereby promoting deubiquitination of BAG6-target proteins
CC       and rescuing them from degradation. Interacts with ricin A chain.
CC       Interacts with VCP and AMFR; both form the VCP/p97-AMFR/gp78
CC       complex. Interacts with SYVN1. Interacts with USP13; the
CC       interaction is direct and may mediate UBL4A deubiquitination (By
CC       similarity). {ECO:0000250|UniProtKB:P46379,
CC       ECO:0000250|UniProtKB:Q9Z1R2}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P46379}. Nucleus
CC       {ECO:0000250|UniProtKB:P46379}. Secreted, exosome
CC       {ECO:0000250|UniProtKB:P46379}. Note=Normally localized in cytosol
CC       and nucleus, it can also be released extracellularly, in exosomes,
CC       by tumor and myeloid dendritic cells.
CC       {ECO:0000250|UniProtKB:P46379}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6MG49-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6MG49-2; Sequence=VSP_040420, VSP_040421;
CC   -!- DOMAIN: The ubiquitin-like domain mediates interaction with the E3
CC       ubiquitin-protein ligase RNF126 which is responsible for the BAG6-
CC       dependent ubiquitination of client proteins. SGTA also binds this
CC       domain and competes with RNF126 to antagonize client protein
CC       ubiquitination and degradation. The ubiquitin-like domain also
CC       mediates the interaction with USP13.
CC       {ECO:0000250|UniProtKB:P46379}.
CC   -!- PTM: Ricin can induce a cleavage by the caspase CASP3. The
CC       released C-terminal peptide induces apoptosis.
CC       {ECO:0000250|UniProtKB:P46379}.
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DR   EMBL; AB018791; BAA76607.1; -; mRNA.
DR   EMBL; BX883045; CAE83997.1; -; Genomic_DNA.
DR   EMBL; CH474121; EDL83534.1; -; Genomic_DNA.
DR   EMBL; BC100141; AAI00142.1; -; mRNA.
DR   RefSeq; NP_001029140.1; NM_001033968.1. [Q6MG49-1]
DR   RefSeq; NP_446061.2; NM_053609.2. [Q6MG49-2]
DR   UniGene; Rn.203343; -.
DR   ProteinModelPortal; Q6MG49; -.
DR   SMR; Q6MG49; -.
DR   BioGrid; 250197; 1.
DR   IntAct; Q6MG49; 2.
DR   MINT; MINT-4566953; -.
DR   STRING; 10116.ENSRNOP00000057557; -.
DR   iPTMnet; Q6MG49; -.
DR   PhosphoSitePlus; Q6MG49; -.
DR   PaxDb; Q6MG49; -.
DR   PRIDE; Q6MG49; -.
DR   Ensembl; ENSRNOT00000001129; ENSRNOP00000001129; ENSRNOG00000000851. [Q6MG49-2]
DR   Ensembl; ENSRNOT00000060832; ENSRNOP00000057557; ENSRNOG00000000851. [Q6MG49-1]
DR   GeneID; 94342; -.
DR   KEGG; rno:94342; -.
DR   UCSC; RGD:71064; rat. [Q6MG49-1]
DR   CTD; 7917; -.
DR   RGD; 71064; Bag6.
DR   eggNOG; KOG4248; Eukaryota.
DR   eggNOG; ENOG410XS9P; LUCA.
DR   GeneTree; ENSGT00390000016199; -.
DR   HOGENOM; HOG000095177; -.
DR   HOVERGEN; HBG002193; -.
DR   InParanoid; Q6MG49; -.
DR   OMA; PMWSSRR; -.
DR   OrthoDB; EOG091G0XSR; -.
DR   PhylomeDB; Q6MG49; -.
DR   TreeFam; TF328437; -.
DR   PRO; PR:Q6MG49; -.
DR   Proteomes; UP000002494; Chromosome 20.
DR   Bgee; ENSRNOG00000000851; -.
DR   ExpressionAtlas; Q6MG49; baseline and differential.
DR   Genevisible; Q6MG49; RN.
DR   GO; GO:0071818; C:BAT3 complex; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0030544; F:Hsp70 protein binding; IEA:Ensembl.
DR   GO; GO:0051787; F:misfolded protein binding; IEA:Ensembl.
DR   GO; GO:0031593; F:polyubiquitin binding; ISS:UniProtKB.
DR   GO; GO:0070628; F:proteasome binding; ISS:UniProtKB.
DR   GO; GO:0005102; F:receptor binding; IEA:Ensembl.
DR   GO; GO:0043022; F:ribosome binding; ISS:UniProtKB.
DR   GO; GO:0015643; F:toxic substance binding; IEA:Ensembl.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR   GO; GO:1990381; F:ubiquitin-specific protease binding; IEA:Ensembl.
DR   GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR   GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0016569; P:covalent chromatin modification; IEA:UniProtKB-KW.
DR   GO; GO:0009790; P:embryo development; ISS:UniProtKB.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR   GO; GO:0071712; P:ER-associated misfolded protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0002429; P:immune response-activating cell surface receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0018393; P:internal peptidyl-lysine acetylation; ISS:UniProtKB.
DR   GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
DR   GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR   GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR   GO; GO:0030324; P:lung development; ISS:UniProtKB.
DR   GO; GO:1904378; P:maintenance of unfolded protein involved in ERAD pathway; IEA:Ensembl.
DR   GO; GO:0030101; P:natural killer cell activation; IEA:Ensembl.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0045861; P:negative regulation of proteolysis; ISS:UniProtKB.
DR   GO; GO:1904294; P:positive regulation of ERAD pathway; IEA:Ensembl.
DR   GO; GO:0010498; P:proteasomal protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR   GO; GO:0042127; P:regulation of cell proliferation; IEP:RGD.
DR   GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR   GO; GO:0007130; P:synaptonemal complex assembly; ISS:UniProtKB.
DR   GO; GO:0071816; P:tail-anchored membrane protein insertion into ER membrane; ISS:UniProtKB.
DR   GO; GO:0006810; P:transport; IEA:UniProtKB-KW.
DR   GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR   InterPro; IPR021925; DUF3538.
DR   InterPro; IPR029071; Ubiquitin-rel_dom.
DR   InterPro; IPR019954; Ubiquitin_CS.
DR   InterPro; IPR000626; Ubiquitin_dom.
DR   Pfam; PF12057; DUF3538; 1.
DR   Pfam; PF00240; ubiquitin; 1.
DR   SMART; SM00213; UBQ; 1.
DR   SUPFAM; SSF54236; SSF54236; 1.
DR   PROSITE; PS00299; UBIQUITIN_1; 1.
DR   PROSITE; PS50053; UBIQUITIN_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Apoptosis; Chaperone;
KW   Chromatin regulator; Complete proteome; Cytoplasm; Differentiation;
KW   Immunity; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW   Secreted; Spermatogenesis; Transport.
FT   CHAIN         1   1146       Large proline-rich protein BAG6.
FT                                /FTId=PRO_0000114899.
FT   DOMAIN       17     92       Ubiquitin-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00214}.
FT   REPEAT      236    265       1. {ECO:0000250|UniProtKB:P46379}.
FT   REPEAT      410    438       2. {ECO:0000250|UniProtKB:P46379}.
FT   REPEAT      589    616       3. {ECO:0000250|UniProtKB:P46379}.
FT   REPEAT      622    650       4. {ECO:0000250|UniProtKB:P46379}.
FT   REGION      236    650       4 X 29 AA approximate repeats.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   REGION     1036   1146       Mediates interaction with UBL4A and GET4
FT                                and is sufficient for the delivery of
FT                                client proteins to the endoplasmic
FT                                reticulum.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   COMPBIAS    196    268       Pro-rich. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00015}.
FT   COMPBIAS    389    711       Pro-rich. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00015}.
FT   SITE       1015   1016       Cleavage; by CASP3.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   MOD_RES       1      1       N-acetylmethionine.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   MOD_RES      96     96       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   MOD_RES     117    117       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   MOD_RES     978    978       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   MOD_RES     987    987       Phosphoserine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   MOD_RES    1067   1067       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   MOD_RES    1095   1095       Phosphoserine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   MOD_RES    1131   1131       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P46379}.
FT   VAR_SEQ     522    522       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:10390159}.
FT                                /FTId=VSP_040420.
FT   VAR_SEQ    1067   1115       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:10390159}.
FT                                /FTId=VSP_040421.
FT   CONFLICT      4      4       S -> N (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT     11     11       M -> V (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT     47     47       A -> R (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT     74     74       D -> E (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT     93     93       Q -> H (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT    114    114       L -> C (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT    189    189       T -> N (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT    264    265       NH -> TQ (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
FT   CONFLICT    567    567       T -> TAQ (in Ref. 1; BAA76607).
FT                                {ECO:0000305}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT        19     87       ipfam:ubiquitin [T]
FT   MYHIT       272    385       ipfam:DUF3538 [T]
FT   MYHIT        43     68       ipat:UBIQUITIN_1 [T]
FT   MYHIT        17     87       ismart:UBQ [T]
FT   MYHIT        17     77       iprf:UBIQUITIN_2 [T]
SQ   SEQUENCE   1146 AA;  120012 MW;  9CAA4CD9C04F3C29 CRC64;
     MEPSDSTSTA MEEPDSLEVL VKTLDSQTRT FIVGAQMNVK EFKEHIAASV SIPSEKQRLI
     YQGRVLQDDK KLQDYNVGGK VIHLVERAPP QTQLPSGASS GTGSASATHG GGPLPGTRGP
     GASGHDRNAN SYVMVGTFNL PSDGSAVDVH INMEQAPIQS EPRVRLVMAQ HMIRDIQTLL
     SRMECRGGTQ AQASQPPPQT PTVASETVAL NSQTSEPVES EAPPREPMES EEMEERPPTQ
     TPELPPSGPA PAGPAPAPET NAPNHPSPAE HVEVLQELQR LQRRLQPFLQ RYCEVLGAAA
     TTDYNNNHEG REEDQRLINL VGESLRLLGN TFVALSDLRC NLACAPPRHL HVVRPMSHYT
     TPMVLQQAAI PIQINVGTTV TMTGNGARPP PAPGAEAASP GSGQASSLPP SSATVDSSTE
     GAPPPGPAPP PATSHPRVIR ISHQSVEPVV MMHMNIQDSG AQPGGVPSAP TGPLGPPGHG
     QSLGQQVPGF PTAPTRVVIA RPTPPQARPS HPGGPPVSGA LQGAGLGTNT SLAQMVSGLV
     GQLLMQPVLV AQGTPGMAPA SASAPATAQA QAPAPAPAPA PAPATASASA GTTNTATTAG
     PAPGGPAQPP PPQPSAADLQ FSQLLGNLLG PAGPGAGGPS LASPTITVAV PGVPAFLQGM
     TEFLQASQAA PPPPPPPPPP PPAPEQQTTP PPGSPSGGTA SPGGLGPESL PPEFFTSVVQ
     GVLSSLLGSL GARAGSSESI AAFIQRLSGS SNIFEPGADG ALGFFGALLS LLCQNFSMVD
     VVMLLHGHFQ PLQRLQPQLR SFFHQHYLGG QEPTSSNIRM ATHTLITGLE EYVRESFSLV
     QVQPGVDIIR TNLEFLQEQF NSIAAHVLHC TDSGFGARLL ELCNQGLFEC LALNLHCLGG
     QQMELAAVIN GRIRRMSRGV NPSLVSWLTT MMGLRLQVVL EHMPVGPDAI LRYVRRIGDP
     PQALPEEPME VQGAERTSPE PQREDASPAP GTTAEEAMSR GPPPAPEGGS RDEQDGASAD
     AEPWAAAVPP EWVPIIQQDI QSQRKVKPQP PLSDAYLSGM PAKRRKTMQG EGPQLLLSEA
     VSRAAKAAGA RPLTSPESLS RDLEAPEVQE SYRQQLRSDI QKRLQEDPNY SPQRFPNAHR
     AFADDP
//