BAG family molecular chaperone regulator 3 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''BAG3''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. BAG3 is involved in
chaperone-assisted selective autophagy.
Function
BAG proteins compete with
Hip-1 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. The protein encoded by this gene contains a
WW domain
The WW domain, (also known as the rsp5-domain or WWP repeating motif) is a modular protein domain that mediates specific interactions with protein ligands. This domain is found in a number of unrelated signaling and structural proteins and may be ...
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.
Clinical significance
BAG gene has been implicated in age related neurodegenerative diseases such as
Alzheimer
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...
's. It has been demonstrated that BAG1 and BAG3 regulate the proteasomal and lysosomal protein elimination pathways, respectively. It has also been shown to be a cause of familial dilated cardiomyopathy.
That BAG3 mutations are responsible for familial dilated cardiomyopathy is confirmed by another study describing 6 new molecular variants (2 missense and 4 premature Stops
). Moreover, the same publication reported that BAG3 polymorphisms are also associated with sporadic forms of the disease together with HSPB7 locus.
In muscle cells, BAG3 cooperates with the molecular chaperones Hsc70 and HspB8 to induce the degradation of mechanically damaged cytoskeleton components in lysosomes. This process is called
chaperone-assisted selective autophagy and is essential for maintaining muscle activity in flies, mice and men.
BAG3 is able to stimulate the expression of
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is comp ...
proteins in response to mechanical tension by activating the
transcription regulators
YAP1 and
WWTR1.
BAG3 balances protein synthesis and protein degradation under mechanical stress.
Interactions
PLCG1 has been shown to
interact with:
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FGFR1
Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and cluster of differentiation, CD331, is a receptor tyrosine kinase whose ligands are specifi ...
,
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CD117,
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CD31,
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Cbl geneEpidermal growth factor receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor rec ...
,KHDRBS1
KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the ''KHDRBS1'' gene.
This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associate ...
,RHOA
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the ''RHOA'' gene. While the effects of RhoA activity are not all well known, it i ...
,
References
Further reading
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External links
GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy
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{{DEFAULTSORT:Bag3
Ageing
Aging-related genes
Aging-related proteins
Co-chaperones