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BAG3

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BAG3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBAG3, BAG-3, BIS, CAIR-1, MFM6, BCL2 associated athanogene 3, BAG cochaperone 3
External IDsOMIM: 603883; MGI: 1352493; HomoloGene: 3162; GeneCards: BAG3; OMA:BAG3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9531

29810

Ensembl

ENSG00000151929

ENSMUSG00000030847

UniProt

O95817

Q9JLV1

RefSeq (mRNA)

NM_004281

NM_013863

RefSeq (protein)

NP_004272

NP_038891

Location (UCSC)Chr 10: 119.65 – 119.68 MbChr 7: 128.13 – 128.15 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

BAG family molecular chaperone regulator 3 is a protein that in humans is encoded by the BAG3 gene. BAG3 is involved in chaperone-assisted selective autophagy.[5][6][7][8][9]

Function

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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 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.[7]

Clinical significance

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BAG gene has been implicated in age related neurodegenerative diseases such as Alzheimer's. It has been demonstrated that BAG1 and BAG3 regulate the proteasomal and lysosomal protein elimination pathways, respectively.[10][11] It has also been shown to be a cause of familial dilated cardiomyopathy.[12] 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.[13]

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.[8]

BAG3 is able to stimulate the expression of cytoskeleton proteins in response to mechanical tension by activating the transcription regulators YAP1 and WWTR1.[9] BAG3 balances protein synthesis and protein degradation under mechanical stress.

Interactions

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PLCG1 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000151929 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030847 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. ^ Carra S, Seguin SJ, Landry J (Feb 2008). "HspB8 and Bag3: a new chaperone complex targeting misfolded proteins to macroautophagy". Autophagy. 4 (2): 237–9. doi:10.4161/auto.5407. PMID 18094623.
  7. ^ a b "Entrez Gene: BAG3 BCL2-associated athanogene 3".
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Further reading

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