Bcl2 Associated Athanogene 3 (BAG3)

BIS; CAIR1; BAG Family Molecular Chaperone Regulator 3; Bcl-2-binding protein Bis; Docking protein CAIR-1

SPN	U511
HGNC	939
MGI	1352493
PubMed	21472004
RGD	1307794
UniProt	O95817
Wiki	BAG3

BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. BAG3 contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. BAG gene has been implicated in age related neurodegenerative diseases as Alzheimer's. It has been demonstrated that BAG1 and BAG 3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.

Reference

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J. Biol. Chem. 274:781-786(1999) [PubMed] [Europe PMC] [Abstract]

"Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death."
Oncogene 18:6183-6190(1999) [PubMed] [Europe PMC] [Abstract]

"CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70."
Oncogene 19:4385-4395(2000) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

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Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

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Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy."
Nat. Genet. 44:450-455(2012) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Mutation in BAG3 causes severe dominant childhood muscular dystrophy."
Ann. Neurol. 65:83-89(2009) [PubMed] [Europe PMC] [Abstract]

"Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy."
Am. J. Hum. Genet. 88:273-282(2011) [PubMed] [Europe PMC] [Abstract]

"BAG3-related myofibrillar myopathy in a Chinese family."
Clin. Genet. 81:394-398(2012) [PubMed] [Europe PMC] [Abstract]

"A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy."
Eur. Heart J. 32:1065-1076(2011) [PubMed] [Europe PMC] [Abstract]

"Dilated cardiomyopathy-associated BAG3 mutations impair Z-disc assembly and enhance sensitivity to apoptosis in cardiomyocytes."
Hum. Mutat. 32:1481-1491(2011) [PubMed] [Europe PMC] [Abstract]