Entry sw: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   18-JAN-2017, entry version 100.
DE   RecName: Full=Large proline-rich protein BAG6;
DE   AltName: Full=BCL2-associated athanogene 6;
DE   AltName: Full=HLA-B-associated transcript 3;
GN   Name=Bag6; Synonyms=Bat3;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
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: Chaperone that plays a key role in various processes
CC       such as apoptosis, insertion of tail-anchored (TA) membrane
CC       proteins to the endoplasmic reticulum membrane and regulation of
CC       chromatin. Key component of the BAG6/BAT3 complex, a cytosolic
CC       multiprotein complex involved in the post-translational delivery
CC       of tail-anchored (TA) membrane proteins to the endoplasmic
CC       reticulum membrane. TA membrane proteins, also named type II
CC       transmembrane proteins, contain a single C-terminal transmembrane
CC       region. BAG6/BAT3 acts by facilitating TA membrane proteins
CC       capture by ASNA1/TRC40: it is recruited to ribosomes synthesizing
CC       membrane proteins, interacts with the transmembrane region of
CC       newly released TA proteins and transfers them to ASNA1/TRC40 for
CC       targeting to the endoplasmic reticulum membrane. Moreover, it
CC       regulates the stability and the degradation of proteins by the
CC       proteasome. For instance, it is required for selective ubiquitin-
CC       mediated degradation of defective nascent chain polypeptides by
CC       the proteasome. In this context, may play a role in immuno-
CC       proteasomes to generate antigenic peptides via targeted
CC       degradation, thereby playing a role in antigen presentation in
CC       immune response. It is also involved in ubiquitin-mediated
CC       proteasomal degradation of proteins of the secretory pathway that
CC       are mislocalized to the cytosol. Binds the mislocalized proteins,
CC       preventing their aggregation in the cytosol, and promotes their
CC       ubiquitination. Participates in endoplasmic reticulum stress-
CC       induced apoptosis via its interaction with AIFM1/AIF by regulating
CC       AIFM1/AIF stability and preventing its degradation. Also required
CC       during spermatogenesis for synaptonemal complex assembly via its
CC       interaction with HSPA2, by inhibiting polyubiquitination and
CC       subsequent proteasomal degradation of HSPA2.
CC       {ECO:0000250|UniProtKB:P46379, ECO:0000250|UniProtKB:Q9Z1R2}.
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       (By similarity). {ECO:0000250|UniProtKB:P46379}.
CC   -!- FUNCTION: Can be released from tumor and dendritic cells in
CC       membrane vesicles or exosomes, and engage NCR3 thereby promoting
CC       natural killer cells (NK) activation and cytotoxicity.
CC       {ECO:0000250|UniProtKB:P46379}.
CC   -!- SUBUNIT: Component of the BAT3 complex, at least composed of
CC       BAG6/BAT3, UBL4A and GET4/TRC35. Interacts with AIFM1, CTCFL,
CC       HSPA2 and p300/EP300. Interacts with ricin A chain. Interacts with
CC       NCR3. Interacts (via ubiquitin-like domain) with RNF126; required
CC       for BAG6-dependent ubiquitination of proteins mislocalized to the
CC       cytosol. {ECO:0000250|UniProtKB:P46379,
CC       ECO:0000250|UniProtKB:Q9Z1R2}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Nucleus
CC       {ECO:0000250}. Note=The C-terminal fragment generated by caspase-3
CC       is cytoplasmic. Also found in extracellular vesicular exosomes in
CC       some tumor cells (By similarity). {ECO:0000250}.
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   -!- PTM: Cleavage by caspase-3 releases a C-terminal peptide that
CC       plays a role in ricin-induced apoptosis. {ECO:0000250}.
CC   -!- SIMILARITY: Contains 1 ubiquitin-like domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00214}.
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   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:0016020; C:membrane; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0031593; F:polyubiquitin binding; ISS:UniProtKB.
DR   GO; GO:0070628; F:proteasome binding; ISS:UniProtKB.
DR   GO; GO:0043022; F:ribosome binding; 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:0002376; P:immune system process; IEA:UniProtKB-KW.
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: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: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: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   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.
FT   REPEAT      410    438       2.
FT   REPEAT      589    616       3.
FT   REPEAT      622    650       4.
FT   REGION      237    650       4 X 29 AA approximate repeats.
FT   COMPBIAS    196    268       Pro-rich.
FT   COMPBIAS    389    711       Pro-rich.
FT   COMPBIAS    558    602       Ala-rich.
FT   SITE       1015   1016       Cleavage; by caspase-3. {ECO:0000250}.
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        17     77       iprf:UBIQUITIN_2 [T]
FT   MYHIT       272    385       ipfam:DUF3538 [T]
FT   MYHIT        43     68       ipat:UBIQUITIN_1 [T]
FT   MYHIT        17     87       ismart:UBQ [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
//