Full text data of BAG1
BAG1
(HAP)
[Confidence: low (only semi-automatic identification from reviews)]
BAG family molecular chaperone regulator 1; BAG-1 (Bcl-2-associated athanogene 1)
BAG family molecular chaperone regulator 1; BAG-1 (Bcl-2-associated athanogene 1)
UniProt
Q99933
ID BAG1_HUMAN Reviewed; 345 AA.
AC Q99933; O75315; Q14414; Q53H32; Q5VZE8; Q5VZE9; Q5VZF0; Q96TG2;
read moreAC Q9Y2V4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=BAG family molecular chaperone regulator 1;
DE Short=BAG-1;
DE AltName: Full=Bcl-2-associated athanogene 1;
GN Name=BAG1; Synonyms=HAP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8524784; DOI=10.1073/pnas.92.25.11465;
RA Zeiner M., Gehring U.;
RT "A protein that interacts with members of the nuclear hormone receptor
RT family: identification and cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11465-11469(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=8812483; DOI=10.1006/geno.1996.0389;
RA Takayama S., Kochel K., Irie S., Inazawa J., Abe T., Sato T.,
RA Druck T., Huebner K., Reed J.C.;
RT "Cloning of cDNAs encoding the human BAG1 protein and localization of
RT the human BAG1 gene to chromosome 9p12.";
RL Genomics 35:494-498(1996).
RN [3]
RP SEQUENCE REVISION TO N-TERMINUS; 79; 84; 90; 245 AND 293.
RA Takayama S.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ANTI-APOPTOTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH STK19.
RC TISSUE=T-cell;
RX PubMed=15986447; DOI=10.1002/ijc.21259;
RA Wadle A., Mischo A., Henrich P.P., Stenner-Lieven F., Scherer C.,
RA Imig J., Petersen G., Pfreundschuh M., Renner C.;
RT "Characterization of Hap/BAG-1 variants as RP1 binding proteins with
RT antiapoptotic activity.";
RL Int. J. Cancer 117:896-904(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Dermoid cancer;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix, and Lung;
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 [9]
RP IDENTIFICATION OF ISOFORMS 1 AND 4, AND ALTERNATIVE INITIATION.
RX PubMed=9396724;
RA Packham G., Brimmell M., Cleveland J.L.;
RT "Mammalian cells express two differently localized Bag-1 isoforms
RT generated by alternative translation initiation.";
RL Biochem. J. 328:807-813(1997).
RN [10]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH BCL2; HSP70 AND HSPA8.
RX PubMed=9305631; DOI=10.1093/emboj/16.16.4887;
RA Takayama S., Bimston D.N., Matsuzawa S.-I., Freeman B.C.,
RA Aime-Sempe C., Xie Z., Morimoto R.I., Reed J.C.;
RT "BAG-1 modulates the chaperone activity of Hsp70/Hsc70.";
RL EMBO J. 16:4887-4896(1997).
RN [11]
RP IDENTIFICATION OF ISOFORMS 1; 3 AND 4, ALTERNATIVE INITIATION,
RP SUBCELLULAR LOCATION, INTERACTION WITH HSPA8, INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9679980;
RA Takayama S., Krajewski S., Krajewska M., Kitada S., Zapata J.M.,
RA Kochel K., Knee D., Scudiero D., Tudor G., Miller G.J., Miyashita T.,
RA Yamada M., Reed J.C.;
RT "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein
RT BAG-1 and its variants in normal tissues and tumor cell lines.";
RL Cancer Res. 58:3116-3131(1998).
RN [12]
RP INTERACTION WITH SIAH1.
RX PubMed=9582267; DOI=10.1093/emboj/17.10.2736;
RA Matsuzawa S., Takayama S., Froesch B.A., Zapata J.M., Reed J.C.;
RT "p53-inducible human homologue of Drosophila seven in absentia (Siah)
RT inhibits cell growth: suppression by BAG-1.";
RL EMBO J. 17:2736-2747(1998).
RN [13]
RP FUNCTION.
RX PubMed=9873016; DOI=10.1074/jbc.274.2.781;
RA Takayama S., Xie Z., Reed J.C.;
RT "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone
RT regulators.";
RL J. Biol. Chem. 274:781-786(1999).
RN [14]
RP INTERACTION WITH NR3C1.
RX PubMed=10477749; DOI=10.1083/jcb.146.5.929;
RA Schneikert J., Huebner S., Martin E., Cato A.B.C.;
RT "A nuclear action of the eukaryotic cochaperone RAP46 in
RT downregulation of glucocorticoid receptor activity.";
RL J. Cell Biol. 146:929-940(1999).
RN [15]
RP INTERACTION WITH PPP1R15A, AND FUNCTION.
RX PubMed=12724406; DOI=10.1128/MCB.23.10.3477-3486.2003;
RA Hung W.J., Roberson R.S., Taft J., Wu D.Y.;
RT "Human BAG-1 proteins bind to the cellular stress response protein
RT GADD34 and interfere with GADD34 functions.";
RL Mol. Cell. Biol. 23:3477-3486(2003).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 222-334 IN COMPLEX WITH
RP HSC70.
RX PubMed=11222862; DOI=10.1126/science.1057268;
RA Sondermann H., Scheufler C., Schneider C., Hohfeld J., Hartl F.U.,
RA Moarefi I.;
RT "Structure of a Bag/Hsc70 complex: convergent functional evolution of
RT Hsp70 nucleotide exchange factors.";
RL Science 291:1553-1557(2001).
RN [19]
RP STRUCTURE BY NMR OF 143-223.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the ubiquitin domain of Bcl-2 binding
RT athanogene-1.";
RL Submitted (AUG-2005) to the PDB data bank.
CC -!- FUNCTION: Inhibits the chaperone activity of HSP70/HSC70 by
CC promoting substrate release. Inhibits the pro-apoptotic function
CC of PPP1R15A, and has anti-apoptotic activity. Markedly increases
CC the anti-cell death function of BCL2 induced by various stimuli.
CC -!- SUBUNIT: Homodimer. Forms a heteromeric complex with HSP70/HSC70.
CC Binds to the ATPase domain of HSP/HSC70 chaperones. Isoform 1,
CC isoform 3 and isoform 4 but not isoform 2 interact with
CC HSPA8/HSC70. Interacts with NR3C1. Interacts with the N-terminal
CC region of STK19. Interacts with PPP1R15A. Interacts with BCL2 in
CC an ATP-dependent manner. Isoform 2 does not interact with BCL2.
CC -!- INTERACTION:
CC P11142:HSPA8; NbExp=10; IntAct=EBI-1030678, EBI-351896;
CC -!- SUBCELLULAR LOCATION: Isoform 1: Nucleus. Cytoplasm. Note=Isoform
CC 1 localizes predominantly to the nucleus.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Nucleus. Note=Isoform
CC 2 localizes to the cytoplasm and shuttles into the nucleus in
CC response to heat shock.
CC -!- SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. Nucleus. Note=Isoform
CC 4 localizes predominantly to the cytoplasm. The cellular
CC background in which it is expressed can influence whether it
CC resides primarily in the cytoplasm or is also found in the
CC nucleus. In the presence of BCL2, localizes to intracellular
CC membranes (what appears to be the nuclear envelope and perinuclear
CC membranes) as well as punctate cytosolic structures suggestive of
CC mitochondria.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=1; Synonyms=BAG-1L, p50;
CC IsoId=Q99933-1; Sequence=Displayed;
CC Name=2; Synonyms=BAG1V, HAPV;
CC IsoId=Q99933-2; Sequence=VSP_000453;
CC Note=Produced by alternative splicing;
CC Name=3; Synonyms=BAG-1M, RAP46;
CC IsoId=Q99933-3; Sequence=VSP_038395;
CC Note=Produced by alternative initiation at Met-72 of isoform 1;
CC Name=4; Synonyms=BAG-1, p32;
CC IsoId=Q99933-4; Sequence=VSP_038394;
CC Note=Produced by alternative initiation at Met-116 of isoform 1;
CC -!- TISSUE SPECIFICITY: Isoform 4 is the most abundantly expressed
CC isoform. It is ubiquitously expressed throughout most tissues,
CC except the liver, colon, breast and uterine myometrium. Isoform 1
CC is expressed in the ovary and testis. Isoform 4 is expressed in
CC several types of tumor cell lines, and at consistently high levels
CC in leukemia and lymphoma cell lines. Isoform 1 is expressed in the
CC prostate, breast and leukemia cell lines. Isoform 3 is the least
CC abundant isoform in tumor cell lines (at protein level).
CC -!- INDUCTION: Up-regulated during differentiation of bladder
CC epithelial cells and down-regulated during differentiation of
CC prostate epithelium.
CC -!- PTM: Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its
CC subsequent proteasomal degradation (Probable).
CC -!- SIMILARITY: Contains 1 BAG domain.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD11467.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAD25045.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAD96469.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon;
CC Sequence=CAA84624.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH72516.1; Type=Erroneous gene model prediction;
CC Sequence=CAH72518.1; Type=Erroneous gene model prediction;
CC Sequence=CAH72741.1; Type=Erroneous gene model prediction;
CC Sequence=CAH72742.1; Type=Erroneous gene model prediction;
CC Sequence=EAW58515.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org//Genes/BAG1ID742ch9p13.html";
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DR EMBL; Z35491; CAA84624.1; ALT_INIT; mRNA.
DR EMBL; U46917; AAD11467.1; ALT_INIT; mRNA.
DR EMBL; AF022224; AAC34258.1; -; mRNA.
DR EMBL; AF116273; AAD25045.1; ALT_INIT; mRNA.
DR EMBL; AK222749; BAD96469.1; ALT_INIT; mRNA.
DR EMBL; AL161445; CAH72516.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL356472; CAH72516.1; JOINED; Genomic_DNA.
DR EMBL; AL161445; CAH72517.1; -; Genomic_DNA.
DR EMBL; AL356472; CAH72517.1; JOINED; Genomic_DNA.
DR EMBL; AL161445; CAH72518.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL356472; CAH72518.1; JOINED; Genomic_DNA.
DR EMBL; AL356472; CAH72741.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL161445; CAH72741.1; JOINED; Genomic_DNA.
DR EMBL; AL356472; CAH72742.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL161445; CAH72742.1; JOINED; Genomic_DNA.
DR EMBL; AL356472; CAH72743.1; -; Genomic_DNA.
DR EMBL; AL161445; CAH72743.1; JOINED; Genomic_DNA.
DR EMBL; CH471071; EAW58514.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58515.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC001936; AAH01936.2; -; mRNA.
DR EMBL; BC014774; AAH14774.2; -; mRNA.
DR RefSeq; NP_001165886.1; NM_001172415.1.
DR RefSeq; NP_004314.5; NM_004323.5.
DR RefSeq; XP_005251578.1; XM_005251521.1.
DR UniGene; Hs.377484; -.
DR PDB; 1HX1; X-ray; 1.90 A; B=222-334.
DR PDB; 1WXV; NMR; -; A=143-223.
DR PDB; 3FZF; X-ray; 2.20 A; B=222-334.
DR PDB; 3FZH; X-ray; 2.00 A; B=222-334.
DR PDB; 3FZK; X-ray; 2.10 A; B=222-334.
DR PDB; 3FZL; X-ray; 2.20 A; B=222-334.
DR PDB; 3FZM; X-ray; 2.30 A; B=222-334.
DR PDB; 3LDQ; X-ray; 1.90 A; B=222-334.
DR PDB; 3M3Z; X-ray; 2.10 A; B=222-334.
DR PDBsum; 1HX1; -.
DR PDBsum; 1WXV; -.
DR PDBsum; 3FZF; -.
DR PDBsum; 3FZH; -.
DR PDBsum; 3FZK; -.
DR PDBsum; 3FZL; -.
DR PDBsum; 3FZM; -.
DR PDBsum; 3LDQ; -.
DR PDBsum; 3M3Z; -.
DR ProteinModelPortal; Q99933; -.
DR SMR; Q99933; 140-331.
DR DIP; DIP-3341N; -.
DR IntAct; Q99933; 12.
DR MINT; MINT-189058; -.
DR PhosphoSite; Q99933; -.
DR DMDM; 296439462; -.
DR PaxDb; Q99933; -.
DR PRIDE; Q99933; -.
DR DNASU; 573; -.
DR Ensembl; ENST00000379704; ENSP00000369026; ENSG00000107262.
DR GeneID; 573; -.
DR KEGG; hsa:573; -.
DR UCSC; uc003zsi.3; human.
DR CTD; 573; -.
DR GeneCards; GC09M033245; -.
DR HGNC; HGNC:937; BAG1.
DR HPA; CAB002486; -.
DR HPA; HPA018121; -.
DR MIM; 601497; gene.
DR neXtProt; NX_Q99933; -.
DR PharmGKB; PA25237; -.
DR eggNOG; NOG72809; -.
DR HOVERGEN; HBG000236; -.
DR InParanoid; Q99933; -.
DR KO; K09555; -.
DR ChiTaRS; BAG1; human.
DR EvolutionaryTrace; Q99933; -.
DR GeneWiki; BAG1; -.
DR GenomeRNAi; 573; -.
DR NextBio; 2337; -.
DR PRO; PR:Q99933; -.
DR ArrayExpress; Q99933; -.
DR Bgee; Q99933; -.
DR CleanEx; HS_BAG1; -.
DR Genevestigator; Q99933; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005057; F:receptor signaling protein activity; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0070389; P:chaperone cofactor-dependent protein refolding; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR InterPro; IPR003103; BAG_domain.
DR InterPro; IPR017093; Molecular_chp_reg_BAG_1.
DR InterPro; IPR000626; Ubiquitin_dom.
DR Pfam; PF02179; BAG; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR PIRSF; PIRSF037029; BAG_1; 1.
DR SMART; SM00264; BAG; 1.
DR SMART; SM00213; UBQ; 1.
DR PROSITE; PS51035; BAG; 1.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing; Apoptosis;
KW Chaperone; Complete proteome; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 345 BAG family molecular chaperone regulator
FT 1.
FT /FTId=PRO_0000088865.
FT REPEAT 96 101 1.
FT REPEAT 102 107 2.
FT REPEAT 108 113 3.
FT REPEAT 114 119 4.
FT REPEAT 120 125 5.
FT REPEAT 126 131 6.
FT REPEAT 132 137 7.
FT DOMAIN 144 224 Ubiquitin-like.
FT DOMAIN 246 326 BAG.
FT REGION 96 137 7 X 6 AA tandem repeat of E-E-X(4).
FT REGION 172 219 Interaction with HSPA8.
FT REGION 216 345 Interaction with PPP1R15A.
FT COMPBIAS 4 82 Arg-rich.
FT MOD_RES 223 223 Phosphoserine.
FT VAR_SEQ 1 115 Missing (in isoform 4).
FT /FTId=VSP_038394.
FT VAR_SEQ 1 71 Missing (in isoform 3).
FT /FTId=VSP_038395.
FT VAR_SEQ 302 345 KDSRLKRKGLVKKVQAFLAECDTVEQNICQETERLQSTNFA
FT LAE -> PTLTLVLNEK (in isoform 2).
FT /FTId=VSP_000453.
FT CONFLICT 45 45 G -> R (in Ref. 2; AAC34258, 5; BAD96469
FT and 8; AAH01936/AAH14774).
FT CONFLICT 79 79 R -> F (in Ref. 2; AAD11467).
FT CONFLICT 84 84 E -> K (in Ref. 2; AAD11467).
FT CONFLICT 90 90 E -> K (in Ref. 2; AAD11467).
FT CONFLICT 245 245 D -> N (in Ref. 2; AAD11467).
FT CONFLICT 293 293 D -> H (in Ref. 2; AAD11467).
FT STRAND 144 149
FT STRAND 151 159
FT STRAND 163 167
FT HELIX 170 180
FT TURN 185 187
FT STRAND 189 192
FT STRAND 195 197
FT STRAND 200 203
FT HELIX 204 207
FT STRAND 211 219
FT HELIX 224 259
FT HELIX 264 272
FT HELIX 275 292
FT HELIX 302 326
SQ SEQUENCE 345 AA; 38779 MW; 8B40EF078C66335F CRC64;
MAQRGGARRP RGDRERLGSR LRALRPGREP RQSEPPAQRG PPPSGRPPAR STASGHDRPT
RGAAAGARRP RMKKKTRRRS TRSEELTRSE ELTLSEEATW SEEATQSEEA TQGEEMNRSQ
EVTRDEESTR SEEVTREEMA AAGLTVTVTH SNEKHDLHVT SQQGSSEPVV QDLAQVVEEV
IGVPQSFQKL IFKGKSLKEM ETPLSALGIQ DGCRVMLIGK KNSPQEEVEL KKLKHLEKSV
EKIADQLEEL NKELTGIQQG FLPKDLQAEA LCKLDRRVKA TIEQFMKILE EIDTLILPEN
FKDSRLKRKG LVKKVQAFLA ECDTVEQNIC QETERLQSTN FALAE
//
ID BAG1_HUMAN Reviewed; 345 AA.
AC Q99933; O75315; Q14414; Q53H32; Q5VZE8; Q5VZE9; Q5VZF0; Q96TG2;
read moreAC Q9Y2V4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 4.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=BAG family molecular chaperone regulator 1;
DE Short=BAG-1;
DE AltName: Full=Bcl-2-associated athanogene 1;
GN Name=BAG1; Synonyms=HAP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8524784; DOI=10.1073/pnas.92.25.11465;
RA Zeiner M., Gehring U.;
RT "A protein that interacts with members of the nuclear hormone receptor
RT family: identification and cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11465-11469(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=8812483; DOI=10.1006/geno.1996.0389;
RA Takayama S., Kochel K., Irie S., Inazawa J., Abe T., Sato T.,
RA Druck T., Huebner K., Reed J.C.;
RT "Cloning of cDNAs encoding the human BAG1 protein and localization of
RT the human BAG1 gene to chromosome 9p12.";
RL Genomics 35:494-498(1996).
RN [3]
RP SEQUENCE REVISION TO N-TERMINUS; 79; 84; 90; 245 AND 293.
RA Takayama S.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ANTI-APOPTOTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH STK19.
RC TISSUE=T-cell;
RX PubMed=15986447; DOI=10.1002/ijc.21259;
RA Wadle A., Mischo A., Henrich P.P., Stenner-Lieven F., Scherer C.,
RA Imig J., Petersen G., Pfreundschuh M., Renner C.;
RT "Characterization of Hap/BAG-1 variants as RP1 binding proteins with
RT antiapoptotic activity.";
RL Int. J. Cancer 117:896-904(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Dermoid cancer;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix, and Lung;
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 [9]
RP IDENTIFICATION OF ISOFORMS 1 AND 4, AND ALTERNATIVE INITIATION.
RX PubMed=9396724;
RA Packham G., Brimmell M., Cleveland J.L.;
RT "Mammalian cells express two differently localized Bag-1 isoforms
RT generated by alternative translation initiation.";
RL Biochem. J. 328:807-813(1997).
RN [10]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH BCL2; HSP70 AND HSPA8.
RX PubMed=9305631; DOI=10.1093/emboj/16.16.4887;
RA Takayama S., Bimston D.N., Matsuzawa S.-I., Freeman B.C.,
RA Aime-Sempe C., Xie Z., Morimoto R.I., Reed J.C.;
RT "BAG-1 modulates the chaperone activity of Hsp70/Hsc70.";
RL EMBO J. 16:4887-4896(1997).
RN [11]
RP IDENTIFICATION OF ISOFORMS 1; 3 AND 4, ALTERNATIVE INITIATION,
RP SUBCELLULAR LOCATION, INTERACTION WITH HSPA8, INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9679980;
RA Takayama S., Krajewski S., Krajewska M., Kitada S., Zapata J.M.,
RA Kochel K., Knee D., Scudiero D., Tudor G., Miller G.J., Miyashita T.,
RA Yamada M., Reed J.C.;
RT "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein
RT BAG-1 and its variants in normal tissues and tumor cell lines.";
RL Cancer Res. 58:3116-3131(1998).
RN [12]
RP INTERACTION WITH SIAH1.
RX PubMed=9582267; DOI=10.1093/emboj/17.10.2736;
RA Matsuzawa S., Takayama S., Froesch B.A., Zapata J.M., Reed J.C.;
RT "p53-inducible human homologue of Drosophila seven in absentia (Siah)
RT inhibits cell growth: suppression by BAG-1.";
RL EMBO J. 17:2736-2747(1998).
RN [13]
RP FUNCTION.
RX PubMed=9873016; DOI=10.1074/jbc.274.2.781;
RA Takayama S., Xie Z., Reed J.C.;
RT "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone
RT regulators.";
RL J. Biol. Chem. 274:781-786(1999).
RN [14]
RP INTERACTION WITH NR3C1.
RX PubMed=10477749; DOI=10.1083/jcb.146.5.929;
RA Schneikert J., Huebner S., Martin E., Cato A.B.C.;
RT "A nuclear action of the eukaryotic cochaperone RAP46 in
RT downregulation of glucocorticoid receptor activity.";
RL J. Cell Biol. 146:929-940(1999).
RN [15]
RP INTERACTION WITH PPP1R15A, AND FUNCTION.
RX PubMed=12724406; DOI=10.1128/MCB.23.10.3477-3486.2003;
RA Hung W.J., Roberson R.S., Taft J., Wu D.Y.;
RT "Human BAG-1 proteins bind to the cellular stress response protein
RT GADD34 and interfere with GADD34 functions.";
RL Mol. Cell. Biol. 23:3477-3486(2003).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 222-334 IN COMPLEX WITH
RP HSC70.
RX PubMed=11222862; DOI=10.1126/science.1057268;
RA Sondermann H., Scheufler C., Schneider C., Hohfeld J., Hartl F.U.,
RA Moarefi I.;
RT "Structure of a Bag/Hsc70 complex: convergent functional evolution of
RT Hsp70 nucleotide exchange factors.";
RL Science 291:1553-1557(2001).
RN [19]
RP STRUCTURE BY NMR OF 143-223.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the ubiquitin domain of Bcl-2 binding
RT athanogene-1.";
RL Submitted (AUG-2005) to the PDB data bank.
CC -!- FUNCTION: Inhibits the chaperone activity of HSP70/HSC70 by
CC promoting substrate release. Inhibits the pro-apoptotic function
CC of PPP1R15A, and has anti-apoptotic activity. Markedly increases
CC the anti-cell death function of BCL2 induced by various stimuli.
CC -!- SUBUNIT: Homodimer. Forms a heteromeric complex with HSP70/HSC70.
CC Binds to the ATPase domain of HSP/HSC70 chaperones. Isoform 1,
CC isoform 3 and isoform 4 but not isoform 2 interact with
CC HSPA8/HSC70. Interacts with NR3C1. Interacts with the N-terminal
CC region of STK19. Interacts with PPP1R15A. Interacts with BCL2 in
CC an ATP-dependent manner. Isoform 2 does not interact with BCL2.
CC -!- INTERACTION:
CC P11142:HSPA8; NbExp=10; IntAct=EBI-1030678, EBI-351896;
CC -!- SUBCELLULAR LOCATION: Isoform 1: Nucleus. Cytoplasm. Note=Isoform
CC 1 localizes predominantly to the nucleus.
CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Nucleus. Note=Isoform
CC 2 localizes to the cytoplasm and shuttles into the nucleus in
CC response to heat shock.
CC -!- SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. Nucleus. Note=Isoform
CC 4 localizes predominantly to the cytoplasm. The cellular
CC background in which it is expressed can influence whether it
CC resides primarily in the cytoplasm or is also found in the
CC nucleus. In the presence of BCL2, localizes to intracellular
CC membranes (what appears to be the nuclear envelope and perinuclear
CC membranes) as well as punctate cytosolic structures suggestive of
CC mitochondria.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=1; Synonyms=BAG-1L, p50;
CC IsoId=Q99933-1; Sequence=Displayed;
CC Name=2; Synonyms=BAG1V, HAPV;
CC IsoId=Q99933-2; Sequence=VSP_000453;
CC Note=Produced by alternative splicing;
CC Name=3; Synonyms=BAG-1M, RAP46;
CC IsoId=Q99933-3; Sequence=VSP_038395;
CC Note=Produced by alternative initiation at Met-72 of isoform 1;
CC Name=4; Synonyms=BAG-1, p32;
CC IsoId=Q99933-4; Sequence=VSP_038394;
CC Note=Produced by alternative initiation at Met-116 of isoform 1;
CC -!- TISSUE SPECIFICITY: Isoform 4 is the most abundantly expressed
CC isoform. It is ubiquitously expressed throughout most tissues,
CC except the liver, colon, breast and uterine myometrium. Isoform 1
CC is expressed in the ovary and testis. Isoform 4 is expressed in
CC several types of tumor cell lines, and at consistently high levels
CC in leukemia and lymphoma cell lines. Isoform 1 is expressed in the
CC prostate, breast and leukemia cell lines. Isoform 3 is the least
CC abundant isoform in tumor cell lines (at protein level).
CC -!- INDUCTION: Up-regulated during differentiation of bladder
CC epithelial cells and down-regulated during differentiation of
CC prostate epithelium.
CC -!- PTM: Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its
CC subsequent proteasomal degradation (Probable).
CC -!- SIMILARITY: Contains 1 BAG domain.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD11467.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAD25045.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAD96469.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon;
CC Sequence=CAA84624.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH72516.1; Type=Erroneous gene model prediction;
CC Sequence=CAH72518.1; Type=Erroneous gene model prediction;
CC Sequence=CAH72741.1; Type=Erroneous gene model prediction;
CC Sequence=CAH72742.1; Type=Erroneous gene model prediction;
CC Sequence=EAW58515.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org//Genes/BAG1ID742ch9p13.html";
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DR EMBL; Z35491; CAA84624.1; ALT_INIT; mRNA.
DR EMBL; U46917; AAD11467.1; ALT_INIT; mRNA.
DR EMBL; AF022224; AAC34258.1; -; mRNA.
DR EMBL; AF116273; AAD25045.1; ALT_INIT; mRNA.
DR EMBL; AK222749; BAD96469.1; ALT_INIT; mRNA.
DR EMBL; AL161445; CAH72516.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL356472; CAH72516.1; JOINED; Genomic_DNA.
DR EMBL; AL161445; CAH72517.1; -; Genomic_DNA.
DR EMBL; AL356472; CAH72517.1; JOINED; Genomic_DNA.
DR EMBL; AL161445; CAH72518.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL356472; CAH72518.1; JOINED; Genomic_DNA.
DR EMBL; AL356472; CAH72741.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL161445; CAH72741.1; JOINED; Genomic_DNA.
DR EMBL; AL356472; CAH72742.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL161445; CAH72742.1; JOINED; Genomic_DNA.
DR EMBL; AL356472; CAH72743.1; -; Genomic_DNA.
DR EMBL; AL161445; CAH72743.1; JOINED; Genomic_DNA.
DR EMBL; CH471071; EAW58514.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58515.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC001936; AAH01936.2; -; mRNA.
DR EMBL; BC014774; AAH14774.2; -; mRNA.
DR RefSeq; NP_001165886.1; NM_001172415.1.
DR RefSeq; NP_004314.5; NM_004323.5.
DR RefSeq; XP_005251578.1; XM_005251521.1.
DR UniGene; Hs.377484; -.
DR PDB; 1HX1; X-ray; 1.90 A; B=222-334.
DR PDB; 1WXV; NMR; -; A=143-223.
DR PDB; 3FZF; X-ray; 2.20 A; B=222-334.
DR PDB; 3FZH; X-ray; 2.00 A; B=222-334.
DR PDB; 3FZK; X-ray; 2.10 A; B=222-334.
DR PDB; 3FZL; X-ray; 2.20 A; B=222-334.
DR PDB; 3FZM; X-ray; 2.30 A; B=222-334.
DR PDB; 3LDQ; X-ray; 1.90 A; B=222-334.
DR PDB; 3M3Z; X-ray; 2.10 A; B=222-334.
DR PDBsum; 1HX1; -.
DR PDBsum; 1WXV; -.
DR PDBsum; 3FZF; -.
DR PDBsum; 3FZH; -.
DR PDBsum; 3FZK; -.
DR PDBsum; 3FZL; -.
DR PDBsum; 3FZM; -.
DR PDBsum; 3LDQ; -.
DR PDBsum; 3M3Z; -.
DR ProteinModelPortal; Q99933; -.
DR SMR; Q99933; 140-331.
DR DIP; DIP-3341N; -.
DR IntAct; Q99933; 12.
DR MINT; MINT-189058; -.
DR PhosphoSite; Q99933; -.
DR DMDM; 296439462; -.
DR PaxDb; Q99933; -.
DR PRIDE; Q99933; -.
DR DNASU; 573; -.
DR Ensembl; ENST00000379704; ENSP00000369026; ENSG00000107262.
DR GeneID; 573; -.
DR KEGG; hsa:573; -.
DR UCSC; uc003zsi.3; human.
DR CTD; 573; -.
DR GeneCards; GC09M033245; -.
DR HGNC; HGNC:937; BAG1.
DR HPA; CAB002486; -.
DR HPA; HPA018121; -.
DR MIM; 601497; gene.
DR neXtProt; NX_Q99933; -.
DR PharmGKB; PA25237; -.
DR eggNOG; NOG72809; -.
DR HOVERGEN; HBG000236; -.
DR InParanoid; Q99933; -.
DR KO; K09555; -.
DR ChiTaRS; BAG1; human.
DR EvolutionaryTrace; Q99933; -.
DR GeneWiki; BAG1; -.
DR GenomeRNAi; 573; -.
DR NextBio; 2337; -.
DR PRO; PR:Q99933; -.
DR ArrayExpress; Q99933; -.
DR Bgee; Q99933; -.
DR CleanEx; HS_BAG1; -.
DR Genevestigator; Q99933; -.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005057; F:receptor signaling protein activity; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0070389; P:chaperone cofactor-dependent protein refolding; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR InterPro; IPR003103; BAG_domain.
DR InterPro; IPR017093; Molecular_chp_reg_BAG_1.
DR InterPro; IPR000626; Ubiquitin_dom.
DR Pfam; PF02179; BAG; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR PIRSF; PIRSF037029; BAG_1; 1.
DR SMART; SM00264; BAG; 1.
DR SMART; SM00213; UBQ; 1.
DR PROSITE; PS51035; BAG; 1.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing; Apoptosis;
KW Chaperone; Complete proteome; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 345 BAG family molecular chaperone regulator
FT 1.
FT /FTId=PRO_0000088865.
FT REPEAT 96 101 1.
FT REPEAT 102 107 2.
FT REPEAT 108 113 3.
FT REPEAT 114 119 4.
FT REPEAT 120 125 5.
FT REPEAT 126 131 6.
FT REPEAT 132 137 7.
FT DOMAIN 144 224 Ubiquitin-like.
FT DOMAIN 246 326 BAG.
FT REGION 96 137 7 X 6 AA tandem repeat of E-E-X(4).
FT REGION 172 219 Interaction with HSPA8.
FT REGION 216 345 Interaction with PPP1R15A.
FT COMPBIAS 4 82 Arg-rich.
FT MOD_RES 223 223 Phosphoserine.
FT VAR_SEQ 1 115 Missing (in isoform 4).
FT /FTId=VSP_038394.
FT VAR_SEQ 1 71 Missing (in isoform 3).
FT /FTId=VSP_038395.
FT VAR_SEQ 302 345 KDSRLKRKGLVKKVQAFLAECDTVEQNICQETERLQSTNFA
FT LAE -> PTLTLVLNEK (in isoform 2).
FT /FTId=VSP_000453.
FT CONFLICT 45 45 G -> R (in Ref. 2; AAC34258, 5; BAD96469
FT and 8; AAH01936/AAH14774).
FT CONFLICT 79 79 R -> F (in Ref. 2; AAD11467).
FT CONFLICT 84 84 E -> K (in Ref. 2; AAD11467).
FT CONFLICT 90 90 E -> K (in Ref. 2; AAD11467).
FT CONFLICT 245 245 D -> N (in Ref. 2; AAD11467).
FT CONFLICT 293 293 D -> H (in Ref. 2; AAD11467).
FT STRAND 144 149
FT STRAND 151 159
FT STRAND 163 167
FT HELIX 170 180
FT TURN 185 187
FT STRAND 189 192
FT STRAND 195 197
FT STRAND 200 203
FT HELIX 204 207
FT STRAND 211 219
FT HELIX 224 259
FT HELIX 264 272
FT HELIX 275 292
FT HELIX 302 326
SQ SEQUENCE 345 AA; 38779 MW; 8B40EF078C66335F CRC64;
MAQRGGARRP RGDRERLGSR LRALRPGREP RQSEPPAQRG PPPSGRPPAR STASGHDRPT
RGAAAGARRP RMKKKTRRRS TRSEELTRSE ELTLSEEATW SEEATQSEEA TQGEEMNRSQ
EVTRDEESTR SEEVTREEMA AAGLTVTVTH SNEKHDLHVT SQQGSSEPVV QDLAQVVEEV
IGVPQSFQKL IFKGKSLKEM ETPLSALGIQ DGCRVMLIGK KNSPQEEVEL KKLKHLEKSV
EKIADQLEEL NKELTGIQQG FLPKDLQAEA LCKLDRRVKA TIEQFMKILE EIDTLILPEN
FKDSRLKRKG LVKKVQAFLA ECDTVEQNIC QETERLQSTN FALAE
//
MIM
601497
*RECORD*
*FIELD* NO
601497
*FIELD* TI
*601497 BCL2-ASSOCIATED ATHANOGENE 1; BAG1
;;RECEPTOR-ASSOCIATED PROTEIN, 46-KD; RAP46
read more*FIELD* TX
CLONING
The oncogene BCL2 (151430) is a membrane protein that blocks a step in a
pathway leading to apoptosis. Takayama et al. (1995) used interaction
cloning to identify Bag1, a mouse protein that binds to Bcl2. The Bag1
protein is rich in glutamic acid residues.
By screening a human liver expression library with activated
glucocorticoid receptor (GCCR; 138040), Zeiner and Gehring (1995) cloned
BAG1, which they called RAP46. The deduced 274-amino acid protein has a
calculated molecular mass of 31 kD. It had an apparent molecular mass of
46 kD by SDS-PAGE. Northern blot analysis detected a 1.4-kb Rap46
transcript in all mouse tissues examined.
Takayama et al. (1996) cloned human BAG1 cDNAs from a fetal brain cDNA
library using the mouse cDNA as a probe. The human cDNA encodes a
predicted 274-amino acid protein, 55 residues longer at the N-terminal
end than the mouse protein. The human BAG1 gene is 80% identical to the
mouse gene sequence. The human protein is also highly acidic, with a pI
of 5.3.
GENE FUNCTION
Takayama et al. (1995) found that overexpression of recombinant Bag1 in
3T3 fibroblasts prevented them from undergoing apoptosis when deprived
of serum.
Zeiner and Gehring (1995) found that recombinant RAP46 interacted with
activated glucocorticoid, androgen (AR; 313700), estrogen (see ESR1;
133430), and progesterone (PGR; 607311) receptors. Binding was dependent
on receptor activation (i.e., release from heat shock proteins), but did
not require the presence of receptor ligands. RAP46 showed a high
affinity for estrogen receptor.
Wang et al. (1996) stated that overproduction of BCL2 occurs frequently
in human cancers and contributes to tumor radio- and chemoresistance by
blocking apoptosis induced by genotoxic injury and other types of
damage. Conversely, reduced levels of BCL2 have been associated with
higher rates of spontaneous and inducible apoptosis in circulating
lymphocytes of persons infected with HIV and some other viruses. The
BCL2-interacting protein, BAG1, enhances the anti-apoptotic effects of
BCL2. Like BAG1, the serine/threonine protein kinase RAF1 (164760) also
cooperates with BCL2 in suppressing apoptosis. Wang et al. (1996) showed
that RAF1 and BAG1 specifically interact in vitro and in yeast 2-hybrid
assays. RAF1 and BAG1 proteins can also be coimmunoprecipitated from
mammalian cells and from insect cells infected with recombinant
baculoviruses encoding these proteins.
Bardelli et al. (1996) found that BAG1 represents a link between growth
factor receptors and anti-apoptotic mechanisms. They showed that BAG1
interacts with both the hepatocyte growth factor receptor (164860) and
the platelet-derived growth factor receptor (173410) and, in both cases,
enhances growth factor-mediated protection from apoptosis. The
C-terminal region of the BAG1 protein was found to be responsible for
binding to the receptors, but the entire BAG1 protein was required for
protection from apoptosis.
Kullmann et al. (1998) demonstrated that mammalian Rap46 bound the hinge
region of the glucocorticoid receptor and inhibited DNA binding and
transactivation by the receptor. Overexpression of Rap46 in mouse
thymoma cells inhibited glucocorticoid-induced apoptosis. Conversely,
treatment with rapamycin, a RAP46 downregulator, enhanced
glucocorticoid-induced apoptosis and transactivation.
Yang et al. (1999) cloned and characterized the human BAG1 gene
promoter. Functional characterization of the BAG1 promoter in vivo
demonstrated that gain-of-function p53 (191170) mutants derived from
human tumors upregulated the transcription of BAG1 RNA and the
expression of a reporter gene from the BAG1 promoter.
MAPPING
Takayama et al. (1996) assigned human BAG1 to chromosome 9 using a panel
of somatic cell hybrid DNAs and localized it to 9p12 by fluorescence in
situ hybridization.
ANIMAL MODEL
By targeted deletion of the Bag1 gene in mice, Gotz et al. (2005) showed
that Bag1 has an essential role in the survival of differentiating
neurons and hematopoietic cells. While Bag1 +/- mice were viable and
appeared normal, Bag1 -/- embryos were growth retarded by embryonic day
13.5 and died between embryonic days 12.5 and 13.5. Histologic analysis
detected abnormalities in the fetal liver and forebrain corresponding to
the onset of endogenous Bag1 expression. Fetal livers of Bag1 -/-
embryos were smaller than those of Bag1 +/- or wildtype littermates,
suggesting a defect in hematopoiesis. In the nervous system, formation
of the telencephalic vesicles was severely disturbed. TUNEL and
propidium-iodide staining indicated massive apoptosis in fetal liver and
increased apoptosis in fetal brains compared with wildtype controls.
Lack of Bag1 did not disturb the primary function of Akt (see AKT1;
164730) or Raf, but it was associated with absence of Bad (603167)
phosphorylation and disturbance of a tripartite complex formed by Akt,
Braf, and Bag1. Bag1 -/- embryos had reduced expression of members of
the inhibitor of apoptosis (see BIRC2; 601712) family.
Maeng et al. (2008) found that transgenic mice with selective
neuron-specific overexpression of Bag1 in the hippocampus did not have
obvious motor, sensory, or learning impairments, but showed less anxious
behavior and had higher spontaneous recovery rates from helplessness
behavior compared to wildtype mice. These transgenic mice also recovered
faster from tests designed to trigger hyperlocomotion or addictive
behaviors. In contrast, heterozygous Bag1 +/- mice showed enhanced
extreme behavioral responses and less recovery in similar tests. The
data suggested that BAG1 may play a role in affective resilience, and
perhaps regulates recovery from behavioral impairments observed in
patients with bipolar affective disorder (see 125480). Maeng et al.
(2008) postulated that the effects are mediated by BAG1 regulation of
glucocorticoid receptor function.
*FIELD* RF
1. Bardelli, A.; Longati, P.; Albero, D.; Goruppi, S.; Schneider,
C.; Ponzetto, C.; Comoglio, P. M.: HGF receptor associates with the
anti-apoptotic protein BAG-1 and prevents cell death. EMBO J. 15:
6205-6212, 1996.
2. Gotz, R.; Wiese, S.; Takayama, S.; Camarero, G. C.; Rossoll, W.;
Schweizer, U.; Troppmair, J.; Jablonka, S.; Holtmann, B.; Reed, J.
C.; Rapp, U. R.; Sendtner, M.: Bag1 is essential for differentiation
and survival of hematopoietic and neuronal cells. Nature Neurosci. 8:
1169-1178, 2005.
3. Kullmann, M.; Schneikert, J.; Moll, J.; Heck, S.; Zeiner, M.; Gehring,
U.; Cato, A. C. B.: RAP46 is a negative regulator of glucocorticoid
receptor action and hormone-induced apoptosis. J. Biol. Chem. 273:
14620-14625, 1998.
4. Maeng, S.; Hunsberger, J. G.; Pearson, B.; Yuan, P.; Wang, Y.;
Wei, Y.; McCammon, J.; Schloesser, R. J.; Zhou, R.; Du, J.; Chen,
G.; McEwen, B.; Reed, J. C.; Manji, H. K.: BAG1 plays a critical
role in regulating recovery from both manic-like and depression-like
behavioral impairments. Proc. Nat. Acad. Sci. 105: 8766-8771, 2008.
5. Takayama, S.; Kochel, K.; Irie, S.; Inazawa, J.; Abe, T.; Sato,
T.; Druck, T.; Huebner, K.; Reed, J. C.: Cloning of cDNAs encoding
the human BAG1 protein and localization of the human BAG1 gene to
chromosome 9p12. Genomics 35: 494-498, 1996.
6. Takayama, S.; Sato, T.; Krajewski, S.; Kochel, K.; Irie, S.; Millan,
J. A.; Reed, J. C.: Cloning and functional analysis of BAG-1: a novel
Bcl-2-binding protein with anti-cell death activity. Cell 80: 279-284,
1995.
7. Wang, H.-G.; Takayama, S.; Rapp, U. R.; Reed, J. C.: Bcl-2 interacting
protein, BAG-1, binds to and activates the kinase Raf-1. Proc. Nat.
Acad. Sci. 93: 7063-7068, 1996.
8. Yang, X.; Pater, A.; Tang, S.-C.: Cloning and characterization
of the human BAG-1 gene promoter: upregulation by tumor-derived p53
mutants. Oncogene 18: 4546-4553, 1999.
9. Zeiner, M.; Gehring, U.: A protein that interacts with members
of the nuclear hormone receptor family: identification and cDNA cloning. Proc.
Nat. Acad. Sci. 92: 11465-11469, 1995.
*FIELD* CN
Cassandra L. Kniffin - updated: 7/29/2009
Patricia A. Hartz - updated: 2/9/2006
Victor A. McKusick - updated: 11/18/1999
Jennifer P. Macke - updated: 8/27/1997
*FIELD* CD
Alan F. Scott: 11/12/1996
*FIELD* ED
alopez: 09/03/2010
terry: 8/31/2010
wwang: 9/4/2009
ckniffin: 7/29/2009
mgross: 3/3/2006
terry: 2/9/2006
mgross: 12/7/1999
terry: 11/18/1999
dkim: 10/1/1998
alopez: 10/6/1997
mark: 11/12/1996
*RECORD*
*FIELD* NO
601497
*FIELD* TI
*601497 BCL2-ASSOCIATED ATHANOGENE 1; BAG1
;;RECEPTOR-ASSOCIATED PROTEIN, 46-KD; RAP46
read more*FIELD* TX
CLONING
The oncogene BCL2 (151430) is a membrane protein that blocks a step in a
pathway leading to apoptosis. Takayama et al. (1995) used interaction
cloning to identify Bag1, a mouse protein that binds to Bcl2. The Bag1
protein is rich in glutamic acid residues.
By screening a human liver expression library with activated
glucocorticoid receptor (GCCR; 138040), Zeiner and Gehring (1995) cloned
BAG1, which they called RAP46. The deduced 274-amino acid protein has a
calculated molecular mass of 31 kD. It had an apparent molecular mass of
46 kD by SDS-PAGE. Northern blot analysis detected a 1.4-kb Rap46
transcript in all mouse tissues examined.
Takayama et al. (1996) cloned human BAG1 cDNAs from a fetal brain cDNA
library using the mouse cDNA as a probe. The human cDNA encodes a
predicted 274-amino acid protein, 55 residues longer at the N-terminal
end than the mouse protein. The human BAG1 gene is 80% identical to the
mouse gene sequence. The human protein is also highly acidic, with a pI
of 5.3.
GENE FUNCTION
Takayama et al. (1995) found that overexpression of recombinant Bag1 in
3T3 fibroblasts prevented them from undergoing apoptosis when deprived
of serum.
Zeiner and Gehring (1995) found that recombinant RAP46 interacted with
activated glucocorticoid, androgen (AR; 313700), estrogen (see ESR1;
133430), and progesterone (PGR; 607311) receptors. Binding was dependent
on receptor activation (i.e., release from heat shock proteins), but did
not require the presence of receptor ligands. RAP46 showed a high
affinity for estrogen receptor.
Wang et al. (1996) stated that overproduction of BCL2 occurs frequently
in human cancers and contributes to tumor radio- and chemoresistance by
blocking apoptosis induced by genotoxic injury and other types of
damage. Conversely, reduced levels of BCL2 have been associated with
higher rates of spontaneous and inducible apoptosis in circulating
lymphocytes of persons infected with HIV and some other viruses. The
BCL2-interacting protein, BAG1, enhances the anti-apoptotic effects of
BCL2. Like BAG1, the serine/threonine protein kinase RAF1 (164760) also
cooperates with BCL2 in suppressing apoptosis. Wang et al. (1996) showed
that RAF1 and BAG1 specifically interact in vitro and in yeast 2-hybrid
assays. RAF1 and BAG1 proteins can also be coimmunoprecipitated from
mammalian cells and from insect cells infected with recombinant
baculoviruses encoding these proteins.
Bardelli et al. (1996) found that BAG1 represents a link between growth
factor receptors and anti-apoptotic mechanisms. They showed that BAG1
interacts with both the hepatocyte growth factor receptor (164860) and
the platelet-derived growth factor receptor (173410) and, in both cases,
enhances growth factor-mediated protection from apoptosis. The
C-terminal region of the BAG1 protein was found to be responsible for
binding to the receptors, but the entire BAG1 protein was required for
protection from apoptosis.
Kullmann et al. (1998) demonstrated that mammalian Rap46 bound the hinge
region of the glucocorticoid receptor and inhibited DNA binding and
transactivation by the receptor. Overexpression of Rap46 in mouse
thymoma cells inhibited glucocorticoid-induced apoptosis. Conversely,
treatment with rapamycin, a RAP46 downregulator, enhanced
glucocorticoid-induced apoptosis and transactivation.
Yang et al. (1999) cloned and characterized the human BAG1 gene
promoter. Functional characterization of the BAG1 promoter in vivo
demonstrated that gain-of-function p53 (191170) mutants derived from
human tumors upregulated the transcription of BAG1 RNA and the
expression of a reporter gene from the BAG1 promoter.
MAPPING
Takayama et al. (1996) assigned human BAG1 to chromosome 9 using a panel
of somatic cell hybrid DNAs and localized it to 9p12 by fluorescence in
situ hybridization.
ANIMAL MODEL
By targeted deletion of the Bag1 gene in mice, Gotz et al. (2005) showed
that Bag1 has an essential role in the survival of differentiating
neurons and hematopoietic cells. While Bag1 +/- mice were viable and
appeared normal, Bag1 -/- embryos were growth retarded by embryonic day
13.5 and died between embryonic days 12.5 and 13.5. Histologic analysis
detected abnormalities in the fetal liver and forebrain corresponding to
the onset of endogenous Bag1 expression. Fetal livers of Bag1 -/-
embryos were smaller than those of Bag1 +/- or wildtype littermates,
suggesting a defect in hematopoiesis. In the nervous system, formation
of the telencephalic vesicles was severely disturbed. TUNEL and
propidium-iodide staining indicated massive apoptosis in fetal liver and
increased apoptosis in fetal brains compared with wildtype controls.
Lack of Bag1 did not disturb the primary function of Akt (see AKT1;
164730) or Raf, but it was associated with absence of Bad (603167)
phosphorylation and disturbance of a tripartite complex formed by Akt,
Braf, and Bag1. Bag1 -/- embryos had reduced expression of members of
the inhibitor of apoptosis (see BIRC2; 601712) family.
Maeng et al. (2008) found that transgenic mice with selective
neuron-specific overexpression of Bag1 in the hippocampus did not have
obvious motor, sensory, or learning impairments, but showed less anxious
behavior and had higher spontaneous recovery rates from helplessness
behavior compared to wildtype mice. These transgenic mice also recovered
faster from tests designed to trigger hyperlocomotion or addictive
behaviors. In contrast, heterozygous Bag1 +/- mice showed enhanced
extreme behavioral responses and less recovery in similar tests. The
data suggested that BAG1 may play a role in affective resilience, and
perhaps regulates recovery from behavioral impairments observed in
patients with bipolar affective disorder (see 125480). Maeng et al.
(2008) postulated that the effects are mediated by BAG1 regulation of
glucocorticoid receptor function.
*FIELD* RF
1. Bardelli, A.; Longati, P.; Albero, D.; Goruppi, S.; Schneider,
C.; Ponzetto, C.; Comoglio, P. M.: HGF receptor associates with the
anti-apoptotic protein BAG-1 and prevents cell death. EMBO J. 15:
6205-6212, 1996.
2. Gotz, R.; Wiese, S.; Takayama, S.; Camarero, G. C.; Rossoll, W.;
Schweizer, U.; Troppmair, J.; Jablonka, S.; Holtmann, B.; Reed, J.
C.; Rapp, U. R.; Sendtner, M.: Bag1 is essential for differentiation
and survival of hematopoietic and neuronal cells. Nature Neurosci. 8:
1169-1178, 2005.
3. Kullmann, M.; Schneikert, J.; Moll, J.; Heck, S.; Zeiner, M.; Gehring,
U.; Cato, A. C. B.: RAP46 is a negative regulator of glucocorticoid
receptor action and hormone-induced apoptosis. J. Biol. Chem. 273:
14620-14625, 1998.
4. Maeng, S.; Hunsberger, J. G.; Pearson, B.; Yuan, P.; Wang, Y.;
Wei, Y.; McCammon, J.; Schloesser, R. J.; Zhou, R.; Du, J.; Chen,
G.; McEwen, B.; Reed, J. C.; Manji, H. K.: BAG1 plays a critical
role in regulating recovery from both manic-like and depression-like
behavioral impairments. Proc. Nat. Acad. Sci. 105: 8766-8771, 2008.
5. Takayama, S.; Kochel, K.; Irie, S.; Inazawa, J.; Abe, T.; Sato,
T.; Druck, T.; Huebner, K.; Reed, J. C.: Cloning of cDNAs encoding
the human BAG1 protein and localization of the human BAG1 gene to
chromosome 9p12. Genomics 35: 494-498, 1996.
6. Takayama, S.; Sato, T.; Krajewski, S.; Kochel, K.; Irie, S.; Millan,
J. A.; Reed, J. C.: Cloning and functional analysis of BAG-1: a novel
Bcl-2-binding protein with anti-cell death activity. Cell 80: 279-284,
1995.
7. Wang, H.-G.; Takayama, S.; Rapp, U. R.; Reed, J. C.: Bcl-2 interacting
protein, BAG-1, binds to and activates the kinase Raf-1. Proc. Nat.
Acad. Sci. 93: 7063-7068, 1996.
8. Yang, X.; Pater, A.; Tang, S.-C.: Cloning and characterization
of the human BAG-1 gene promoter: upregulation by tumor-derived p53
mutants. Oncogene 18: 4546-4553, 1999.
9. Zeiner, M.; Gehring, U.: A protein that interacts with members
of the nuclear hormone receptor family: identification and cDNA cloning. Proc.
Nat. Acad. Sci. 92: 11465-11469, 1995.
*FIELD* CN
Cassandra L. Kniffin - updated: 7/29/2009
Patricia A. Hartz - updated: 2/9/2006
Victor A. McKusick - updated: 11/18/1999
Jennifer P. Macke - updated: 8/27/1997
*FIELD* CD
Alan F. Scott: 11/12/1996
*FIELD* ED
alopez: 09/03/2010
terry: 8/31/2010
wwang: 9/4/2009
ckniffin: 7/29/2009
mgross: 3/3/2006
terry: 2/9/2006
mgross: 12/7/1999
terry: 11/18/1999
dkim: 10/1/1998
alopez: 10/6/1997
mark: 11/12/1996