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BAG3 (Bcl-2 associated athanogene 3)

Identity

Other namesBAG-3
BIS
CAIR-1
HGNC (Hugo) BAG3
LocusID (NCBI) 9531
Location 10q26.11
Location_base_pair Starts at 121410882 and ends at 121437329 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description The gene encompasses 26449 bases, 4 exons.
Transcription 2608 nucleotides mRNA.

Protein

Description 575 amino acids. 74 kDa protein, belonging to the evolutionary conserved family of BAG domain- containing proteins.
Expression BAG3 protein is constitutively expressed in muscle and a few other normal cell types, and in some tumors; its expression can be induced by stressors in a number of cell types.
Localisation BAG3 is a cytoplasmatic protein, particularly concentrated in the rough endoplasmic reticulum; a slightly different molecular weight, a doublet form or a nuclear localisation can be observed in some cell types and/or following cell exposure to stressors.
Function Through its BAG domain, BAG3 protein binds with high affinity to the ATPase domain of Hsc70 and regulates its chaperone activity in a Hip-modulated manner; through its PXXP region, BAG3 binds to the SH3 domain of PLC-gamma and forms an epidermal growth factor (EGF)-regulated ternary complex; the proline-rich repeat appears to be involved in regulating cell adhesion and migration, through an indirect effect on focal adhesion kinase (FAK) and its downstream partners; BAG3 knockout mice develop a fulminant myopathy; downmodulation of BAG3 protein levels enhance cell apoptotic response to several inducers, while hyperexpression protects cells from apoptosis.
Homology Other members of BAG family.

Mutations

Note Unknown.

Implicated in

Entity B-chronic lymphocytic leukaemia
Disease Expression of BAG3 gene in leukaemic cell samples from a study on 24 B-CLL-affected patients was detected by RT-PCR and immunofluorescence. Downmodulation of its levels by antisense ODNs resulted in enhancing cytochrome c release, caspase 3 activation and appearance of hypodiploid elements in response to fludarabine.
  
Entity Childhood acute lymphoblastic leukemia
Disease Expression of BAG3 gene in leukaemic cell samples from a study on 11 ALL- affected patients was detected by immunofluorescence. Downmodulation of its levels by antisense ODNs resulted in stimulating caspase 3 activity and enhancing by more that 100% the percentages of apoptotic elements in primary cultures, either untreated or incubated with cytosine arabinoside.
  
Entity Thyroid Carcinomas
Disease BAG3 was expressed in human thyroid carcinoma cell lines; small interfering RNA-mediated downmodulation of its levels significantly enhanced NPA cell apoptotic response to TRAIL. The protein was not detectable in 19 of 20 specimens of normal thyroid or goiters, whereas 54 of 56 analyzed carcinomas (15 follicular carcinomas, 28 papillary carcinomas, and 13 anaplastic carcinomas) were clearly positive for BAG3 expression.
  

External links

Nomenclature
HGNC (Hugo)BAG3   939
Cards
AtlasBAG3ID43160ch10q26
Entrez_Gene (NCBI)BAG3  9531  BCL2-associated athanogene 3
GeneCards (Weizmann)BAG3
Ensembl (Hinxton)ENSG00000151929 [Gene_View]  chr10:121410882-121437329 [Contig_View]  BAG3 [Vega]
AceView (NCBI)BAG3
Genatlas (Paris)BAG3
WikiGenes9531
SOURCE (Princeton)NM_004281
Genomic and cartography
GoldenPath (UCSC)BAG3  -  10q26.11   chr10:121410882-121437329 +  10q25.2-q26.2   [Description]    (hg19-Feb_2009)
EnsemblBAG3 - 10q25.2-q26.2 [CytoView]
Mapping of homologs : NCBIBAG3 [Mapview]
OMIM603883   612954   613881   
Gene and transcription
Genbank (Entrez)AF071218 AF095193 AF127139 AK222800 AK291333
RefSeq transcript (Entrez)NM_004281
RefSeq genomic (Entrez)AC_000142 NC_000010 NC_018921 NG_016125 NT_030059 NW_001838006 NW_004929376
Consensus coding sequences : CCDS (NCBI)BAG3
Cluster EST : UnigeneHs.523309 [ NCBI ]
CGAP (NCI)Hs.523309
Alternative Splicing : Fast-db (Paris)GSHG0003731
Alternative Splicing GalleryENSG00000151929
Gene ExpressionBAG3 [ NCBI-GEO ]     BAG3 [ SEEK ]   BAG3 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95817 (Uniprot)
NextProtO95817  [Medical]
With graphics : InterProO95817
Splice isoforms : SwissVarO95817 (Swissvar)
Domaine pattern : Prosite (Expaxy)BAG (PS51035)    WW_DOMAIN_1 (PS01159)    WW_DOMAIN_2 (PS50020)   
Domains : Interpro (EBI)BAG_domain    WW_dom   
Related proteins : CluSTrO95817
Domain families : Pfam (Sanger)BAG (PF02179)    WW (PF00397)   
Domain families : Pfam (NCBI)pfam02179    pfam00397   
Domain families : Smart (EMBL)BAG (SM00264)  WW (SM00456)  
DMDM Disease mutations9531
Blocks (Seattle)O95817
Human Protein AtlasENSG00000151929
Peptide AtlasO95817
HPRD04860
IPIIPI00641582   IPI00639961   
Protein Interaction databases
DIP (DOE-UCLA)O95817
IntAct (EBI)O95817
FunCoupENSG00000151929
BioGRIDBAG3
InParanoidO95817
Interologous Interaction database O95817
IntegromeDBBAG3
STRING (EMBL)BAG3
Ontologies - Pathways
Ontology : AmiGOprotein binding  cytoplasm  cytosol  plasma membrane  protein folding  brain development  extrinsic apoptotic signaling pathway via death domain receptors  negative regulation of striated muscle cell apoptotic process  spinal cord development  Z disc  protein complex binding  neuron projection  negative regulation of apoptotic process  chaperone binding  cellular response to mechanical stimulus  
Ontology : EGO-EBIprotein binding  cytoplasm  cytosol  plasma membrane  protein folding  brain development  extrinsic apoptotic signaling pathway via death domain receptors  negative regulation of striated muscle cell apoptotic process  spinal cord development  Z disc  protein complex binding  neuron projection  negative regulation of apoptotic process  chaperone binding  cellular response to mechanical stimulus  
REACTOMEBAG3
Protein Interaction DatabaseBAG3
Wikipedia pathwaysBAG3
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)BAG3
SNP (GeneSNP Utah)BAG3
SNP : HGBaseBAG3
Genetic variants : HAPMAPBAG3
1000_GenomesBAG3 
ICGC programENSG00000151929 
Somatic Mutations in Cancer : COSMICBAG3 
CONAN: Copy Number AnalysisBAG3 
Mutations and Diseases : HGMDBAG3
OMIM603883    612954    613881   
GENETestsBAG3
Disease Genetic AssociationBAG3
Huge Navigator BAG3 [HugePedia]  BAG3 [HugeCancerGEM]
Genomic VariantsBAG3  BAG3 [DGVbeta]
Exome VariantBAG3
dbVarBAG3
ClinVarBAG3
snp3D : Map Gene to Disease9531
General knowledge
Homologs : HomoloGeneBAG3
Homology/Alignments : Family Browser (UCSC)BAG3
Phylogenetic Trees/Animal Genes : TreeFamBAG3
Chemical/Protein Interactions : CTD9531
Chemical/Pharm GKB GenePA25239
Clinical trialBAG3
Cancer Resource (Charite)ENSG00000151929
Other databases
Probes
Litterature
PubMed104 Pubmed reference(s) in Entrez
CoreMineBAG3
iHOPBAG3

Bibliography

Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death.
Lee JH, Takahashi T, Yasuhara N, Inazawa J, Kamada S, Tsujimoto Y
Oncogene. 1999 ; 18 (46) : 6183-6190.
PMID 10597216
 
CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70.
Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E
Oncogene. 2000 ; 19 (38) : 4385-4395.
PMID 10980614
 
Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein.
Antoku K, Maser RS, Scully WJ Jr, Delach SM, Johnson DE
Biochemical and biophysical research communications. 2001 ; 286 (5) : 1003-1010.
PMID 11527400
 
The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines.
Liao Q, Ozawa F, Friess H, Zimmermann A, Takayama S, Reed JC, Kleeff J, Bł║chler MW
FEBS letters. 2001 ; 503 (2-3) : 151-157.
PMID 11513873
 
Induction of Bis, a Bcl-2-binding protein, in reactive astrocytes of the rat hippocampus following kainic acid-induced seizure.
Lee MY, Kim SY, Choi JS, Choi YS, Jeon MH, Lee JH, Kim IK, Lee JH
Experimental & molecular medicine. 2002 ; 34 (2) : 167-171.
PMID 12085992
 
Reactive astrocytes express bis, a bcl-2-binding protein, after transient forebrain ischemia.
Lee MY, Kim SY, Shin SL, Choi YS, Lee JH, Tsujimoto Y, Lee JH
Experimental neurology. 2002 ; 175 (2) : 338-346.
PMID 12061864
 
CAIR-1/BAG-3 abrogates heat shock protein-70 chaperone complex-mediated protein degradation: accumulation of poly-ubiquitinated Hsp90 client proteins.
Doong H, Rizzo K, Fang S, Kulpa V, Weissman AM, Kohn EC
The Journal of biological chemistry. 2003 ; 278 (31) : 28490-28500.
PMID 12750378
 
Regulation by heavy metals and temperature of the human BAG-3 gene, a modulator of Hsp70 activity.
Pagliuca MG, Lerose R, Cigliano S, Leone A
FEBS letters. 2003 ; 541 (1-3) : 11-15.
PMID 12706811
 
BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis.
Romano MF, Festa M, Pagliuca G, Lerose R, Bisogni R, Chiurazzi F, Storti G, Volpe S, Venuta S, Turco MC, Leone A
Cell death and differentiation. 2003 ; 10 (3) : 383-385.
PMID 12700638
 
BAG3 protein regulates cell survival in childhood acute lymphoblastic leukemia cells.
Romano MF, Festa M, Petrella A, Rosati A, Pascale M, Bisogni R, Poggi V, Kohn EC, Venuta S, Turco MC, Leone A
Cancer biology & therapy. 2003 ; 2 (5) : 508-510.
PMID 14614315
 
BAG3 protein regulates stress-induced apoptosis in normal and neoplastic leukocytes.
Bonelli P, Petrella A, Rosati A, Romano MF, Lerose R, Pagliuca MG, Amelio T, Festa M, Martire G, Venuta S, Turco MC, Leone A
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 ; 18 (2) : 358-360.
PMID 14628070
 
Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27.
Seo YJ, Jeon MH, Lee JH, Lee YJ, Youn HJ, Ko JH, Lee JH
Experimental & molecular medicine. 2005 ; 37 (6) : 624-630.
PMID 16391524
 
BAG3 deficiency results in fulminant myopathy and early lethality.
Homma S, Iwasaki M, Shelton GD, Engvall E, Reed JC, Takayama S
The American journal of pathology. 2006 ; 169 (3) : 761-773.
PMID 16936253
 
CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins.
Kassis JN, Guancial EA, Doong H, Virador V, Kohn EC
Experimental cell research. 2006 ; 312 (15) : 2962-2971.
PMID 16859681
 
The antiapoptotic protein BAG3 is expressed in thyroid carcinomas and modulates apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand.
Chiappetta G, Ammirante M, Basile A, Rosati A, Festa M, Monaco M, Vuttariello E, Pasquinelli R, Arra C, Zerilli M, Todaro M, Stassi G, Pezzullo L, Gentilella A, Tosco A, Pascale M, Marzullo L, Belisario MA, Turco MC, Leone A
The Journal of clinical endocrinology and metabolism. 2007 ; 92 (3) : 1159-1163.
PMID 17164298
 
Evidence for BAG3 modulation of HIV-1 gene transcription.
Rosati A, Leone A, Del Valle L, Amini S, Khalili K, Turco MC
Journal of cellular physiology. 2007 ; 210 (3) : 676-683.
PMID 17187345
 
Apoptosis inhibition in cancer cells: a novel molecular pathway that involves BAG3 protein.
Rosati A, Ammirante M, Gentilella A, Basile A, Festa M, Pascale M, Marzullo L, Belisario MA, Tosco A, Franceschelli S, Moltedo O, Pagliuca G, Lerose R, Turco MC
The international journal of biochemistry & cell biology. 2007 ; 39 (7-8) : 1337-1342.
PMID 17493862
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written08-2007Arturo Leone, Alessandra Rosati, Massimo Ammirante, Maria Caterina Turco
Department of Pharmaceutical Sciences, University of Salerno, 84084, Fisciano (SA), Italy

Citation

This paper should be referenced as such :
Leone A, Rosati A, Ammirante M, Turco MC . BAG3 (Bcl-2 associated athanogene 3). Atlas Genet Cytogenet Oncol Haematol. August 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/BAG3ID43160ch10q26.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38487/1/08-2007-BAG3ID43160ch10q26.pdf   [ Bibliographic record ]

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indexed on : Mon Mar 31 08:58:10 CEST 2014

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