BAG3 (Bcl-2 associated athanogene 3)

Identity

Other names	BAG-3
	BIS
	CAIR-1
HGNC	BAG3
Location	10q26.11
Location_base_pair	Starts at 121400872 and ends at 121427319 bp from pter ( according to hg18-Mar_2006).

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	BAG3   939
Entrez_Gene	BAG3  9531  BCL2-associated athanogene 3
	Cards
Atlas	BAG3ID43160ch10q26
GeneCards	BAG3
Ensembl	ENSG00000151929 [Gene_View]  BAG3 [Vega]
Genatlas	BAG3
	Genomic and cartography
GoldenPath	BAG3  -  10q26.11   chr10:121400872-121427319 +  10q25.2-q26.2   [Description]    (hg18-Mar_2006)
Ensembl	BAG3 - 10q25.2-q26.2 [CytoView]
NCBI	Mapview
OMIM	603883 Disease map [OMIM]
HomoloGene	BAG3
	Gene and transcription
Genbank	AF071218 [ ENTREZ ]
Genbank	AF095193 [ ENTREZ ]
Genbank	AF127139 [ ENTREZ ]
Genbank	AK222800 [ ENTREZ ]
Genbank	AK291333 [ ENTREZ ]
RefSeq	NM_004281 [ SRS ]    NM_004281 [ ENTREZ ]
RefSeq	AC_000053 [ SRS ]    AC_000053 [ ENTREZ ]
RefSeq	AC_000142 [ SRS ]    AC_000142 [ ENTREZ ]
RefSeq	NC_000010 [ SRS ]    NC_000010 [ ENTREZ ]
RefSeq	NT_030059 [ SRS ]    NT_030059 [ ENTREZ ]
RefSeq	NW_001838006 [ SRS ]    NW_001838006 [ ENTREZ ]
RefSeq	NW_924884 [ SRS ]    NW_924884 [ ENTREZ ]
CCDS	BAG3 CCDS - NCBI
AceView	BAG3 AceView - NCBI
Unigene	Hs.712591 [ SRS ]    Hs.712591 [ NCBI ]
Fast-db	16902 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O95817 [ SRS]    O95817 [ EXPASY ]     O95817 [ INTERPRO ]     O95817 [ UNIPROT ] O95817 [ VarSplice FASTA ]
Prosite	PS51035 BAG [ SRS ]    PS51035 BAG [ Expasy ]
Prosite	PS01159 WW_DOMAIN_1 [ SRS ]    PS01159 WW_DOMAIN_1 [ Expasy ]
Prosite	PS50020 WW_DOMAIN_2 [ SRS ]    PS50020 WW_DOMAIN_2 [ Expasy ]
Interpro	IPR003103 BAG [ SRS ]    IPR003103 BAG [ EBI ]
Interpro	IPR001202 WW_Rsp5_WWP [ SRS ]    IPR001202 WW_Rsp5_WWP [ EBI ]
CluSTr	O95817
Pfam	PF02179 BAG [ SRS ]    PF02179 BAG [ Sanger ]    pfam02179 [ NCBI-CDD ]
Pfam	PF00397 WW [ SRS ]    PF00397 WW [ Sanger ]    pfam00397 [ NCBI-CDD ]
Smart	SM00264 BAG [EMBL]
Smart	SM00456 WW [EMBL]
Blocks	O95817
HPRD	04860
	Protein Interaction databases
DIP	O95817
IntAct	O95817
	Polymorphism : SNP, mutations, diseases
OMIM	603883    [ map ]
GENETests	603883
SNP	BAG3 [dbSNP-NCBI]
SNP	NM_004281 [SNP-NCI]
SNP	BAG3 [GeneSNPs - Utah]  BAG3] [HGBASE - SRS]
HAPMAP	BAG3 [HAPMAP]
COSMIC	BAG3 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	BAG3
Genetic Association	BAG3
CDC HuGE	BAG3
	General knowledge
Family Browser	BAG3 [UCSC Family Browser]
SOURCE	NM_004281
SMD	Hs.712591
SAGE	Hs.712591
GO	protein binding [Amigo]  protein binding
GO	cellular_component [Amigo]  cellular_component
GO	cytosol [Amigo]  cytosol
GO	protein folding [Amigo]  protein folding
GO	apoptosis [Amigo]  apoptosis
GO	anti-apoptosis [Amigo]  anti-apoptosis
GO	Hsp70/Hsc70 protein regulator activity [Amigo]  Hsp70/Hsc70 protein regulator activity
PubGene	BAG3
TreeFam	BAG3
CTD	9531 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	BAG3 Related clones (RZPD - Berlin)
	PubMed
PubMed	29 Pubmed reference(s) in Entrez

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, Bˆºchler 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

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Last year publications	automatic search in PubMed

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Contributor(s)

Written	08-2007	Arturo 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:19:57 2008