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BAG3 (Bcl-2 associated athanogene 3)

Written2007-08Arturo Leone, Alessandra Rosati, Massimo Ammirante, Maria Caterina Turco
Department of Pharmaceutical Sciences, University of Salerno, 84084, Fisciano (SA), Italy
Updated2014-02Morena d'Avenia, Luana Guerriero, Alessandra Rosati, Maria Caterina Turco
Department of Pharmaceutical, Biomedical Sciences (FARMABIOMED), University of Salerno, Fisciano (SA), Italy

Abstract Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain. BAG3 is induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter. In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70. These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. BAG3 is expressed also in several tumor types where it sustains cell survival, resistance to therapy, and/or motility and metastatization (Rosati et al., 2011).

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Other aliasBAG-3
HGNC (Hugo) BAG3
LocusID (NCBI) 9531
Atlas_Id 43160
Location 10q26.11  [Link to chromosome band 10q26]
Location_base_pair Starts at 121410882 and ends at 121437329 bp from pter ( according to hg19-Feb_2009)  [Mapping BAG3.png]
Fusion genes
(updated 2016)
BAG3 (10q26.11) / BAG3 (10q26.11)BAG3 (10q26.11) / SFTPB (2p11.2)


  Green: gene; blue: transcript mRNA; red: coding sequence; black: exons.
Description The gene encompasses 33450 bases, 4 exons.
Transcription 2608 nucleotides mRNA.
Pseudogene Chromosome 10: 121442639-121443335 reverse strand. Name: RP11-179H18.7-001; transcript: ENST00000441872.
Chromosome 10: 121435973-121436791 forward strand. Name: PGOHUM00000238940; parent protein: ENSP00000358081; parent gene: ENSG00000151929.
Variant: OTTHUMT00000050663. Exons: 5. Transcript length: 1146 bps. Translation length: 325 residues.


Description 575 amino acids. 74 kDa protein, belonging to the evolutionary conserved family of BAG domain-containing proteins.
Expression Under physiological conditions, BAG3 expression appears to be restricted to few cell types including skeletal muscle cells and cardiomyocytes (Hishiya et al., 2010; De Marco et al., 2011; De Marco et al., 2013). Its expression, however, can be induced in different normal cell types (leukocytes, epithelial, glial and retinal cells) by a variety of stressors, such as oxidants, high temperature, serum deprivation, and it is thought to contribute to stress resistance (Rosati et al., 2007; Pagliuca et al., 2003; Rosati et al., 2009; Ammirante et al., 2010). In contrast to normal cells, BAG3 expression is abundant in several primary tumors or tumor cell lines, where it is thought to give a survival advantage (Rosati et al., 2011). Among those melanoma cells, pancreatic adenocarcinoma cells, colon cancer, liver cancer, T-lynph Jurkat cancer, leukemias, kidney HEK-293, Lung A549, prostate cancer LnCap, cervix cancer Hela, bone cancer U20S, breast cancer cells MCF7.
Localisation BAG3 is mainly 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. BAG3 protein is also released from stressed cardiomyocytes and Pancreatic Adeno Carcinoma cells (PDAC) and can be detected in sera of patients with chronic heart failure (HF) or PDAC (De Marco et al., 2013; Falco et al., 2013), as well as in cells surnatants.
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. BAG3 levels increase during myoblast differentiation, suggesting that its biological role is relevant for differentiated myocytes and not for immature cells. This is in agreement with the observation that BAG3 deletion causes a lethal cardiomyopathy not in embryos, but in postnatal mice. BAG3 mutations may cause abnormal Z-disc assembly and sensitization to apoptosis in cultured cardiomyocytes. More recently it has been shown that BAG3 is essential for homeostasis of mechanically stressed cells. BAG3 is in fact an important component of the chaperone-assisted autophagy (CASA) pathway leading to selective lysosomal degradation of unfolded proteins. In muscle cells the CASA machinery is located at the Z-disk and appears to be essential for disposal of unfolded mechano-sensors and cytoskeleton proteins resulting from mechanical tension. Impairment of the CASA machinery results in z-disk disruption in contracting muscles (Ulbricht et al., 2013; Ulbricht and Höhfeld, 2013).
Homology Other members of BAG family.


Note Several reports associate BAG3 mutations with myopathy. A mutated form of BAG3, i.e. heterozygous Pro209Leu, causes childhood cardiomyopathy and a severe and progressive muscle weakess (Selcen et al., 2009). Non-synonymous BAG3 SNPs or others truncated BAG3 forms were reported to correlate with familiar dilated cardiomyopathy (Villard et al., 2011) and stress-cardiomyopathy also known as Takotsubo cardiomyopathy (Citro et al., 2013). Finally, two heterozygous BAG3 gene mutations, which cause abnormal Z-disc assembly and increased sensitivity to apoptosis in cultured cardiomyocytes, were identified in patients with familial DCM (Arimura et al., 2011).

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 (Romano et al., 2003).
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 than 100% the percentages of apoptotic elements in primary cultures, either untreated or incubated with cytosine arabinoside (Romano et al., 2003).
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 (Li et al., 2013).
Entity Pancreatic adenocarcinomas
Disease BAG3 protein is expressed in PDACs, but is not expressed in the surrounding nonneoplastic tissue. Survival is significantly shorter in patients with high BAG3 expression than in those with low BAG3 expression. Furthermore, BAG3 expression in PDAC-derived cell lines protects from apoptosis and confers resistance to gemcitabine, offering a partial explanation for the survival data. Indeed BAG3 has a relevant role in PDAC biology, and BAG3 expression level might be a potential marker for prediction of patient outcome (Falco et al., 2013; Rosati et al., 2012).
Entity Colorectal carcinomas
Disease Bag3 is distinctly expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620, and WiDr at both mRNA and protein levels. Carcinoma shows stronger Bag-3 expression than adjacent NNM by IHC and Western blot. Metastatic carcinoma more frequently expressed Bag-3 mRNA in lymph node and liver than in primary carcinoma. Immunohistochemically, Bag-3 expression is seen to gradually decrease from carcinoma, adenoma to NNM. There is a positive correlation between Bag-3 expression and TNM staging and GRP94 expression, but no relationship to patient age or sex, tumor size, depth of invasion, lymphatic or venous invasion, lymph node metastasis, differentiation or prognosis of colorectal carcinomas. Aberrant Bag-3 expression might be involved in colorectal adenoma-adenocarcinoma sequence and subsequent progression (Yang et al., 2013).


IKK{gamma} protein is a target of BAG3 regulatory activity in human tumor growth.
Ammirante M, Rosati A, Arra C, Basile A, Falco A, Festa M, Pascale M, d'Avenia M, Marzullo L, Belisario MA, De Marco M, Barbieri A, Giudice A, Chiappetta G, Vuttariello E, Monaco M, Bonelli P, Salvatore G, Di Benedetto M, Deshmane SL, Khalili K, Turco MC, Leone A.
Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7497-502. doi: 10.1073/pnas.0907696107. Epub 2010 Apr 5.
PMID 20368414
Dilated cardiomyopathy-associated BAG3 mutations impair Z-disc assembly and enhance sensitivity to apoptosis in cardiomyocytes.
Arimura T, Ishikawa T, Nunoda S, Kawai S, Kimura A.
Hum Mutat. 2011 Dec;32(12):1481-91. doi: 10.1002/humu.21603. Epub 2011 Sep 29.
PMID 21898660
Polymorphisms of the antiapoptotic protein bag3 may play a role in the pathogenesis of tako-tsubo cardiomyopathy.
Citro R, d'Avenia M, De Marco M, Giudice R, Mirra M, Ravera A, Silverio A, Farina R, Silvestri F, Gravina P, Villa F, Puca AA, De Windt L, De Laurenzi V, Bossone E, Turco MC, Piscione F.
Int J Cardiol. 2013 Sep 30;168(2):1663-5. doi: 10.1016/j.ijcard.2013.03.050. Epub 2013 Apr 11.
PMID 23582692
Detection of soluble BAG3 and anti-BAG3 antibodies in patients with chronic heart failure.
De Marco M, Falco A, Basile A, Rosati A, Festa M, d'Avenia M, Pascale M, Dal Piaz F, Bisogni R, Barcaroli D, Coppola G, Piscione F, Gigantino A, Citro R, De Rosa R, Vitulano G, Virtuoso N, Manganelli F, Palermo E, Siano F, Rosato G, Hahne M, Tiberti C, De Laurenzi V, Turco MC.
Cell Death Dis. 2013 Feb 14;4:e495. doi: 10.1038/cddis.2013.8.
PMID 23412388
BAG3 is a novel serum biomarker for pancreatic adenocarcinomas.
Falco A, Rosati A, Festa M, Basile A, De Marco M, d'Avenia M, Pascale M, Dal Piaz F, Tavano F, Di Mola FF, di Sebastiano P, Berloco PB, Nudo F, Caraglia M, Febbraro A, Barcaroli D, Scarpa A, Pezzilli R, De Laurenzi V, Turco MC.
Am J Gastroenterol. 2013 Jul;108(7):1178-80. doi: 10.1038/ajg.2013.128.
PMID 23821002
BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress.
Hishiya A, Kitazawa T, Takayama S.
Circ Res. 2010 Nov 12;107(10):1220-31. doi: 10.1161/CIRCRESAHA.110.225649. Epub 2010 Sep 30.
PMID 20884878
PKCdelta-mediated phosphorylation of BAG3 at Ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer FRO cells.
Li N, Du ZX, Zong ZH, Liu BQ, Li C, Zhang Q, Wang HQ.
Oncogene. 2013 Sep 19;32(38):4539-48. doi: 10.1038/onc.2012.466. Epub 2012 Oct 29.
PMID 23108398
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 Lett. 2003 Apr 24;541(1-3):11-5.
PMID 12706811
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 Biol Ther. 2003 Sep-Oct;2(5):508-10.
PMID 14614315
Expression of the antiapoptotic protein BAG3 is a feature of pancreatic adenocarcinoma and its overexpression is associated with poorer survival.
Rosati A, Bersani S, Tavano F, Dalla Pozza E, De Marco M, Palmieri M, De Laurenzi V, Franco R, Scognamiglio G, Palaia R, Fontana A, di Sebastiano P, Donadelli M, Dando I, Medema JP, Dijk F, Welling L, di Mola FF, Pezzilli R, Turco MC, Scarpa A.
Am J Pathol. 2012 Nov;181(5):1524-9. doi: 10.1016/j.ajpath.2012.07.016. Epub 2012 Aug 31.
PMID 22944597
Identification of a Btk-BAG3 complex induced by oxidative stress.
Rosati A, Di Salle E, Luberto L, Quinto I, Scala G, Turco MC, Pascale M.
Leukemia. 2009 Apr;23(4):823-4. doi: 10.1038/leu.2009.23. Epub 2009 Feb 12.
PMID 19212330
BAG3: a multifaceted protein that regulates major cell pathways.
Rosati A, Graziano V, De Laurenzi V, Pascale M, Turco MC.
Cell Death Dis. 2011 Apr 7;2:e141. doi: 10.1038/cddis.2011.24. (REVIEW)
PMID 21472004
Evidence for BAG3 modulation of HIV-1 gene transcription.
Rosati A, Leone A, Del Valle L, Amini S, Khalili K, Turco MC.
J Cell Physiol. 2007 Mar;210(3):676-83.
PMID 17187345
Mutation in BAG3 causes severe dominant childhood muscular dystrophy.
Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, Engel AG.
Ann Neurol. 2009 Jan;65(1):83-9. doi: 10.1002/ana.21553.
PMID 19085932
Tension-induced autophagy: may the chaperone be with you.
Ulbricht A, Hohfeld J.
Autophagy. 2013 Jun 1;9(6):920-2. doi: 10.4161/auto.24213. Epub 2013 Mar 21.
PMID 23518596
A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy.
Villard E, Perret C, Gary F, Proust C, Dilanian G, Hengstenberg C, Ruppert V, Arbustini E, Wichter T, Germain M, Dubourg O, Tavazzi L, Aumont MC, DeGroote P, Fauchier L, Trochu JN, Gibelin P, Aupetit JF, Stark K, Erdmann J, Hetzer R, Roberts AM, Barton PJ, Regitz-Zagrosek V; Cardiogenics Consortium, Aslam U, Duboscq-Bidot L, Meyborg M, Maisch B, Madeira H, Waldenstrom A, Galve E, Cleland JG, Dorent R, Roizes G, Zeller T, Blankenberg S, Goodall AH, Cook S, Tregouet DA, Tiret L, Isnard R, Komajda M, Charron P, Cambien F.
Eur Heart J. 2011 May;32(9):1065-76. doi: 10.1093/eurheartj/ehr105. Epub 2011 Apr 1.
PMID 21459883
Bag-3 expression is involved in pathogenesis and progression of colorectal carcinomas.
Yang X, Tian Z, Gou WF, Takahashi H, Yu M, Xing YN, Takano Y, Zheng HC.
Histol Histopathol. 2013 Sep;28(9):1147-56. Epub 2013 Apr 4.
PMID 23553442


This paper should be referenced as such :
M d'Avenia, L Guerriero, A Rosati, MC Turco
BAG3 (Bcl-2 associated athanogene 3)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):704-708.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Leone, A ; Rosati, A ; Ammirante, M ; Turco, MC. BAG3 (Bcl-2 associated athanogene 3). Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):87-88.

External links

HGNC (Hugo)BAG3   939
LRG (Locus Reference Genomic)LRG_742
Entrez_Gene (NCBI)BAG3  9531  BCL2 associated athanogene 3
AliasesBAG-3; BIS; CAIR-1; MFM6
GeneCards (Weizmann)BAG3
Ensembl hg19 (Hinxton)ENSG00000151929 [Gene_View]  chr10:121410882-121437329 [Contig_View]  BAG3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000151929 [Gene_View]  chr10:121410882-121437329 [Contig_View]  BAG3 [Vega]
ICGC DataPortalENSG00000151929
TCGA cBioPortalBAG3
AceView (NCBI)BAG3
Genatlas (Paris)BAG3
SOURCE (Princeton)BAG3
Genetics Home Reference (NIH)BAG3
Genomic and cartography
GoldenPath hg19 (UCSC)BAG3  -     chr10:121410882-121437329 +  10q25.2-q26.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)BAG3  -     10q25.2-q26.2   [Description]    (hg38-Dec_2013)
EnsemblBAG3 - 10q25.2-q26.2 [CytoView hg19]  BAG3 - 10q25.2-q26.2 [CytoView hg38]
Mapping of homologs : NCBIBAG3 [Mapview hg19]  BAG3 [Mapview hg38]
OMIM603883   612954   613881   
Gene and transcription
Genbank (Entrez)AF071218 AF095193 AF127139 AK222800 AK291333
RefSeq transcript (Entrez)NM_004281
RefSeq genomic (Entrez)NC_000010 NC_018921 NG_016125 NT_030059 NW_004929376
Consensus coding sequences : CCDS (NCBI)BAG3
Cluster EST : UnigeneHs.523309 [ NCBI ]
CGAP (NCI)Hs.523309
Alternative Splicing GalleryENSG00000151929
Gene ExpressionBAG3 [ NCBI-GEO ]   BAG3 [ EBI - ARRAY_EXPRESS ]   BAG3 [ SEEK ]   BAG3 [ MEM ]
Gene Expression Viewer (FireBrowse)BAG3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9531
GTEX Portal (Tissue expression)BAG3
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95817   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO95817  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO95817
Splice isoforms : SwissVarO95817
Domaine pattern : Prosite (Expaxy)BAG (PS51035)    WW_DOMAIN_1 (PS01159)    WW_DOMAIN_2 (PS50020)   
Domains : Interpro (EBI)BAG_domain    WW_dom   
Domain families : Pfam (Sanger)BAG (PF02179)    WW (PF00397)   
Domain families : Pfam (NCBI)pfam02179    pfam00397   
Domain families : Smart (EMBL)BAG (SM00264)  WW (SM00456)  
Conserved Domain (NCBI)BAG3
DMDM Disease mutations9531
Blocks (Seattle)BAG3
Human Protein AtlasENSG00000151929
Peptide AtlasO95817
IPIIPI00641582   IPI00639961   
Protein Interaction databases
IntAct (EBI)O95817
Ontologies - Pathways
Ontology : AmiGOadenyl-nucleotide exchange factor activity  adenyl-nucleotide exchange factor activity  protein binding  cytoplasm  cytosol  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  regulation of catalytic activity  regulation of catalytic activity  protein stabilization  chaperone binding  cellular response to mechanical stimulus  extrinsic apoptotic signaling pathway in absence of ligand  regulation of cellular response to heat  
Ontology : EGO-EBIadenyl-nucleotide exchange factor activity  adenyl-nucleotide exchange factor activity  protein binding  cytoplasm  cytosol  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  regulation of catalytic activity  regulation of catalytic activity  protein stabilization  chaperone binding  cellular response to mechanical stimulus  extrinsic apoptotic signaling pathway in absence of ligand  regulation of cellular response to heat  
REACTOMEO95817 [protein]
REACTOME Pathways3371453 [pathway]   
NDEx NetworkBAG3
Atlas of Cancer Signalling NetworkBAG3
Wikipedia pathwaysBAG3
Orthology - Evolution
GeneTree (enSembl)ENSG00000151929
Phylogenetic Trees/Animal Genes : TreeFamBAG3
Homologs : HomoloGeneBAG3
Homology/Alignments : Family Browser (UCSC)BAG3
Gene fusions - Rearrangements
Fusion Cancer (Beijing)BAG3 [10q26.11]  -  SFTPB [2p11.2]  [FUSC003619]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBAG3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BAG3
Exome Variant ServerBAG3
ExAC (Exome Aggregation Consortium)BAG3 (select the gene name)
Genetic variants : HAPMAP9531
Genomic Variants (DGV)BAG3 [DGVbeta]
DECIPHER (Syndromes)10:121410882-121437329  ENSG00000151929
CONAN: Copy Number AnalysisBAG3 
ICGC Data PortalBAG3 
TCGA Data PortalBAG3 
Broad Tumor PortalBAG3
OASIS PortalBAG3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBAG3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDBAG3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)Leiden Muscular Dystrophy pages
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch BAG3
DgiDB (Drug Gene Interaction Database)BAG3
DoCM (Curated mutations)BAG3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BAG3 (select a term)
NCG5 (London)BAG3
Cancer3DBAG3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM603883    612954    613881   
Orphanet635    18405   
Genetic Testing Registry BAG3
NextProtO95817 [Medical]
Huge Navigator BAG3 [HugePedia]
snp3D : Map Gene to Disease9531
BioCentury BCIQBAG3
ClinGenBAG3 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9531
Chemical/Pharm GKB GenePA25239
Clinical trialBAG3
canSAR (ICR)BAG3 (select the gene name)
PubMed149 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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