BAG6_PIG
ID BAG6_PIG Reviewed; 1128 AA.
AC A5D9M6; A5D9M5; A5D9M7; B9TSQ3;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Large proline-rich protein BAG6 {ECO:0000305};
DE AltName: Full=BCL2-associated athanogene 6 {ECO:0000250|UniProtKB:P46379};
DE AltName: Full=HLA-B-associated transcript 3 {ECO:0000312|EMBL:ABX82810.1};
GN Name=BAG6 {ECO:0000250|UniProtKB:P46379};
GN Synonyms=BAT3 {ECO:0000312|EMBL:ABX82810.1};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kim J.H., Jeon J.T.;
RT "Identification of single-nucleotide polymorphisms in coding sequences of
RT genes in the SLA class III region by direct sequencing.";
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=17625002; DOI=10.1186/gb-2007-8-7-r139;
RA Humphray S.J., Scott C.E., Clark R., Marron B., Bender C., Camm N.,
RA Davis J., Jenks A., Noon A., Patel M., Sehra H., Yang F., Rogatcheva M.B.,
RA Milan D., Chardon P., Rohrer G., Nonneman D., de Jong P., Meyers S.N.,
RA Archibald A., Beever J.E., Schook L.B., Rogers J.;
RT "A high utility integrated map of the pig genome.";
RL Genome Biol. 8:R139.1-R139.34(2007).
CC -!- FUNCTION: ATP-independent molecular chaperone preventing the
CC aggregation of misfolded and hydrophobic patches-containing proteins.
CC Functions as part of a cytosolic protein quality control complex, the
CC BAG6/BAT3 complex, which maintains these client proteins in a soluble
CC state and participates in their proper delivery to the endoplasmic
CC reticulum or alternatively can promote their sorting to the proteasome
CC where they undergo degradation. The BAG6/BAT3 complex is involved in
CC the post-translational delivery of tail-anchored/type II transmembrane
CC proteins to the endoplasmic reticulum membrane. Recruited to ribosomes,
CC it 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 be
CC properly delivered to the endoplasmic reticulum are ubiquitinated by
CC RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are
CC sorted to the proteasome. SGTA which prevents the recruitment of RNF126
CC to BAG6 may negatively regulate the ubiquitination and the proteasomal
CC degradation of client proteins. Similarly, the BAG6/BAT3 complex also
CC functions as a sorting platform for proteins of the secretory pathway
CC that are 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 their
CC 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 their
CC proper delivery to the proteasome. BAG6 is also required for selective
CC ubiquitin-mediated degradation of defective nascent chain polypeptides
CC by the proteasome. In this context, it may participate in the
CC production of antigenic peptides and play a role in antigen
CC presentation in immune response. BAG6 is also involved in endoplasmic
CC reticulum stress-induced pre-emptive quality control, a mechanism that
CC selectively attenuates the translocation of newly synthesized proteins
CC into the endoplasmic reticulum and reroutes them to the cytosol for
CC proteasomal degradation. BAG6 may ensure the proper degradation of
CC these proteins and thereby protects the endoplasmic reticulum from
CC protein overload upon stress. By inhibiting the polyubiquitination and
CC subsequent proteasomal degradation of HSPA2 it may also play a role in
CC the assembly of the synaptonemal complex during spermatogenesis. Also
CC positively regulates apoptosis by interacting with and stabilizing the
CC proapoptotic factor AIFM1. By controlling the steady-state expression
CC of the IGF1R receptor, indirectly regulates the insulin-like growth
CC factor receptor signaling pathway. {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 p300/EP300,
CC enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase
CC p53/TP53 transcriptional activity. When nuclear, may also act as a
CC component of some chromatin regulator complex that regulates histone 3
CC 'Lys-4' dimethylation (H3K4me2). {ECO:0000250|UniProtKB:P46379}.
CC -!- FUNCTION: Released extracellularly via exosomes, it is a ligand of the
CC 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 complex,
CC at least composed of BAG6, UBL4A and GET4/TRC35. Interacts with GET4;
CC the interaction is direct and localizes BAG6 in the cytosol. Interacts
CC with UBL4A; the interaction is direct and required for UBL4A protein
CC stability. Interacts with AIFM1. Interacts with HSPA2. Interacts with
CC CTCFL. Interacts with p300/EP300. Interacts (via ubiquitin-like domain)
CC with RNF126; required for BAG6-dependent ubiquitination of proteins
CC mislocalized to the cytosol. Interacts (via ubiquitin-like domain) with
CC SGTA; SGTA competes with RNF126 by binding the same region of BAG6,
CC thereby promoting deubiquitination of BAG6-target proteins and rescuing
CC them from degradation. Interacts with ricin A chain. Interacts with VCP
CC and AMFR; both form the VCP/p97-AMFR/gp78 complex. Interacts with
CC SYVN1. Interacts with USP13; the interaction is direct and may mediate
CC UBL4A deubiquitination. Interacts with ZFAND2B. Interacts with KPNA2.
CC Interacts with UBQLN4 (By similarity). {ECO:0000250|UniProtKB:P46379,
CC ECO:0000250|UniProtKB:Q9Z1R2}.
CC -!- INTERACTION:
CC A5D9M6; PRO_0000036687 [Q04561]: rep; Xeno; NbExp=2; IntAct=EBI-11702016, EBI-11701979;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P46379}. Nucleus {ECO:0000250|UniProtKB:P46379}.
CC Secreted, extracellular exosome {ECO:0000250|UniProtKB:P46379}.
CC Note=Normally localized in cytosol and nucleus, it can also be released
CC extracellularly, in exosomes, 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=A5D9M6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A5D9M6-2; Sequence=VSP_040437, VSP_040438;
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 mediates
CC the interaction with USP13. {ECO:0000250|UniProtKB:P46379}.
CC -!- PTM: Ricin can induce a cleavage by the caspase CASP3. The released C-
CC terminal peptide induces apoptosis. {ECO:0000250|UniProtKB:P46379}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAN59677.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; EU282341; ABX82810.1; -; mRNA.
DR EMBL; BX548169; CAN59675.1; -; Genomic_DNA.
DR EMBL; BX548169; CAN59676.1; -; Genomic_DNA.
DR EMBL; BX548169; CAN59677.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_001138854.1; NM_001145382.1. [A5D9M6-1]
DR RefSeq; XP_005665832.1; XM_005665775.2.
DR AlphaFoldDB; A5D9M6; -.
DR SMR; A5D9M6; -.
DR IntAct; A5D9M6; 1.
DR STRING; 9823.ENSSSCP00000001500; -.
DR PaxDb; A5D9M6; -.
DR PeptideAtlas; A5D9M6; -.
DR PRIDE; A5D9M6; -.
DR Ensembl; ENSSSCT00005055896; ENSSSCP00005034429; ENSSSCG00005033087. [A5D9M6-1]
DR Ensembl; ENSSSCT00025108140; ENSSSCP00025048949; ENSSSCG00025077573. [A5D9M6-1]
DR Ensembl; ENSSSCT00025108155; ENSSSCP00025048953; ENSSSCG00025077573. [A5D9M6-1]
DR Ensembl; ENSSSCT00030090218; ENSSSCP00030041572; ENSSSCG00030062793. [A5D9M6-1]
DR Ensembl; ENSSSCT00030090318; ENSSSCP00030041615; ENSSSCG00030062793. [A5D9M6-1]
DR Ensembl; ENSSSCT00040092025; ENSSSCP00040040602; ENSSSCG00040061565. [A5D9M6-1]
DR Ensembl; ENSSSCT00040092992; ENSSSCP00040041083; ENSSSCG00040061565. [A5D9M6-1]
DR Ensembl; ENSSSCT00045063617; ENSSSCP00045044891; ENSSSCG00045032435. [A5D9M6-1]
DR Ensembl; ENSSSCT00045063926; ENSSSCP00045045125; ENSSSCG00045032435. [A5D9M6-1]
DR Ensembl; ENSSSCT00050010383; ENSSSCP00050004452; ENSSSCG00050006825. [A5D9M6-1]
DR Ensembl; ENSSSCT00050010432; ENSSSCP00050004473; ENSSSCG00050006825. [A5D9M6-1]
DR Ensembl; ENSSSCT00055055086; ENSSSCP00055043953; ENSSSCG00055025612. [A5D9M6-1]
DR Ensembl; ENSSSCT00055055423; ENSSSCP00055044239; ENSSSCG00055025612. [A5D9M6-1]
DR Ensembl; ENSSSCT00065050051; ENSSSCP00065021657; ENSSSCG00065036083. [A5D9M6-1]
DR Ensembl; ENSSSCT00065050074; ENSSSCP00065021668; ENSSSCG00065036083. [A5D9M6-1]
DR GeneID; 100153950; -.
DR KEGG; ssc:100153950; -.
DR CTD; 7917; -.
DR eggNOG; KOG4248; Eukaryota.
DR HOGENOM; CLU_012159_0_0_1; -.
DR InParanoid; A5D9M6; -.
DR OrthoDB; 1233552at2759; -.
DR TreeFam; TF328437; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR Genevisible; A5D9M6; SS.
DR GO; GO:0071818; C:BAT3 complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0070628; F:proteasome binding; ISS:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; ISS:UniProtKB.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0061857; P:endoplasmic reticulum stress-induced pre-emptive quality control; ISS:UniProtKB.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; 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: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:0010498; P:proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045995; P:regulation of embryonic development; ISS:UniProtKB.
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:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR InterPro; IPR021925; BAG6.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR019954; Ubiquitin_CS.
DR Pfam; PF12057; BAG6; 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; Cytoplasm; Differentiation; Immunity; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Secreted; Spermatogenesis;
KW Transport.
FT CHAIN 1..1128
FT /note="Large proline-rich protein BAG6"
FT /id="PRO_0000403751"
FT DOMAIN 17..92
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT REPEAT 236..265
FT /note="1"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT REPEAT 410..438
FT /note="2"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT REPEAT 569..596
FT /note="3"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT REPEAT 602..630
FT /note="4"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT REGION 87..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 236..630
FT /note="4 X 29 AA approximate repeats"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT REGION 380..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 456..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 648..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 939..1128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1006..1036
FT /note="Required for interaction with GET4"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT REGION 1018..1128
FT /note="Sufficient for the delivery of client proteins to
FT the endoplasmic reticulum"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT REGION 1054..1111
FT /note="BAG-similar domain, required and sufficient for
FT interaction with UBL4A"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOTIF 1008..1050
FT /note="Nuclear localization site"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT COMPBIAS 92..107
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..220
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..263
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..405
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 406..420
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 566..581
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..680
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 957..971
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 997..998
FT /note="Cleavage; by CASP3"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 117
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 960
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 969
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 1049
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 1077
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT MOD_RES 1113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46379"
FT VAR_SEQ 522
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040437"
FT VAR_SEQ 1049..1097
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040438"
FT CONFLICT 725
FT /note="F -> S (in Ref. 1; ABX82810)"
FT /evidence="ECO:0000305"
FT CONFLICT 996
FT /note="Q -> L (in Ref. 1; ABX82810)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1128 AA; 118627 MW; AE1E659921C292B8 CRC64;
MEPNDSTSTT MEEPESLEVL VKTLDSQTRT FIVGAQMNVK EFKEHIAASV SIPSEKQRLI
YQGRVLQDDK KLQEYNVGGK VIHLVERAPP QTQLPSGASS GTGSASATHG GGPPPGTRGP
GASVHDRNAN SYVMVGTFNL PSDGSAVDVH INMEQAPIQS EPRVRLVMAQ HMIRDIQTLL
SRMECRGGSQ AQHSQPPSQM PTVAPEPVAL SSQTSESVES EVPPREPMAA EEVEERASAQ
SPGLSPSGPA PAGPTPAPET NAPNHPSPAE YVEVLQELQR LESRLQPFLQ RYYEVLGAAA
TTDYNNNQEG REEDQRLINL VGESLRLLGN TFVALSDLRC NLACAPPRHL HVVRPMSHYT
TPMVLQQAAI PIQINVGTTV TMTGNGTRPP PTPNAEAPPP GPGQASSLAP SSTTVESSTE
GAPPPGPAPP PAASHPRVIR ISHQSVEPVV MMHMNIQDSG TQPGGVPSAP TGPLGPTGHG
QTLGQQVPGF PTAPTRVVIA RPTPPQSRPS HPGGPPVSGA LPGAGLGTNA SLAQMVSGLV
GQLLMQPVLV AQGTPGMAPP PAPATASASA GTTNTATTAG PAPGGPAQPP PPQPSASDLQ
FSQLLGNLLG PAGPGAGGPG MTSPTITVAM PGVPAFLQGM TDFLQATQTA APPAPPPPPP
PPPPAPEQQT APPPGSPPGG AGSPGGLGPE SLPLEFFTSV VQGVLSSLLG SLGARAGSSE
SIAAFIQRLS GSSNIFEPGA DGALGFFGAL LSLLCQNFSM VDVVMLLHGH FQPLQRLQPQ
LRSFFHQHYL GGQEPTPGNI RTATHTLITG LEEYVRESFS LVQVQPGVDI IRTNLEFLQE
QFNSIAAHVM HCTDSGFGAR LLELCNQGLF ECLALNLHCL GGQQMELAAV INGRIRRMSR
GVNPSLVSWL TTMMGLRLQV VLEHMPVGPD AILRYVRRVG DPPQPLPEEP MEVQGSERTS
PEPQRENASP APGTTAEEAM SRGPPPAPEG GSRDEQDGAA AETEPWAAAV PPEWVPIIQQ
DIQSQRKVKP QPPLSDAYLS GMPAKRRKTM QGEGPQLLLS EAVSRAAKAA GARPLTSPES
LSRDLEAPEV QESYRQQLRA DIQKRLQEDP NYSPQRFPNA HRAFAEDP
