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FLASH GENE
Symbol BAG3 contributors: mct - updated : 17-02-2014
HGNC name BCL2-associated athanogene 3
HGNC id 939
DNA
TYPE functioning gene
STRUCTURE 26.45 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure two of the three putative heat shock-responsive elements (HSEs) in promoter interact with the heat shock factor HSF1
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 - 2608 - 575 - 2009 19352495
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
blood / hematopoieticspleen   moderately
Cardiovascularvessel     Homo sapiens
Digestiveliver   moderately
Endocrinepancreas   highly
Nervousbrain   moderately
Reproductivemale systemprostate  highly
Respiratorylung   moderately
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Lymphoid    
Muscularstriatumskeletal   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
cell lineage
cell lines Hela cells, pancreatic cancer cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two WW domains at the N-terminus, interacting with the PPDY motif of RAPGEF6
  • one poly Ser domain
  • a WW domain and a proline-rich region with SH3-binding motifs, suggesting that it may interact with proteins relevant to signal transduction
  • two conserved IPV (Ile-Pro-Val) motifs mediating its binding to HSPB8
  • two BAG domains at the C-terminus (for binding to Bcl2)
  • secondary structure beta strands in WW domains
    conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to murine Bag3
    Homologene
    FAMILY
  • BAG family
  • CATEGORY chaperone/stress , regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text
  • mobilization under stress, from the cytosol toward the rough endoplasmic reticulum
  • localizes at Z-disc in the striated muscles
  • basic FUNCTION
  • inhibiting the chaperone activity of Hsp 70/Hsc 70 by promoting substrate release and Hsp-mediated proteasomal degradation
  • antiapoptotic molecule induced by proteasome inhibitors in various cancer cells at the transcriptional level
  • HSPB8 is responsible for recognizing the misfolded proteins whereas BAG3, at least in part through its proline-rich domain, might recruit and activate the macroautophagy machinery in close proximity to the chaperone-loaded substrates
  • forming complexes with BCL2, resulting in an enhancement of its anti-apoptotic activity and a decrease in the apoptosis induced via BAX or FAS
  • regulates motility and adhesion of epithelial cancer cells
  • responsible for macroautophagy stimulation
  • dual regulation of BAG3 in apoptosis suggests a key role for BAG3 in cancer cell resistance to apoptosis
  • Z-disk-associated protein, having antiapoptotic properties
  • co-chaperone that might prevent the accumulation of denatured proteins by regulating sHsp activity and by targeting their substrate proteins for degradation
  • has critical roles in regulating actin organization, cell adhesion, cell motility and tumor metastasis
  • could bind specific SH3-containing proteins that would allow BAG3 to play a role in signal transduction pathways (BAG3 associates with actin at the leading edge of migrating cells and controls cell motility)
  • mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins
  • having ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli
  • co-chaperone protein with antiapoptotic function, which localizes at Z-disc in the striated muscles
  • essential for the interaction between ERK and its phosphatase DUSP6, as a consequence its removal results in reduced binding of DUSP6 to ERK and sustained ERK phosphorylation and cell-cycle arrest in the G1 phase
  • regulates epithelial-mesenchymal transition and angiogenesis in human hepatocellular carcinoma
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS cardiovascular
    PATHWAY
    metabolism
    signaling
    a component
  • form a stable molecular complex with the chaperone cohort protein BAG3
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to Hsp70/Hsc70 (ATPase domain), BCL2, PLC-gamma
  • can bind to HSPB8, and HSPB6 (interaction between HSPB6 and BAG3 requires the same regions that are involved in the HSPB8-BAG3)
  • RAPGEF6 is a BAG3-interacting protein
  • co-chaperone BAG3 directly interacts with RAPGEF6 to regulate integrin-mediated cell adhesion
  • stabilized JUND mRNA, which was, at least in part, responsible for the promotion of serum starvation mediated-growth inhibition by BAG3
  • HSPA5 was a novel partner interacting with BAG3 (through direct interaction BAG3 could prevent the antiapoptotic effect of HSPA5 upon genotoxic stress)
  • cell & other
    REGULATION
    induced by heat and metal (zinc, cadmium) exposure
    Other regulated by heat shock factor 1
    ASSOCIATED DISORDERS
    corresponding disease(s) MFMB , CMD1HH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in many epithelial cancer cell lines, especially adenocarcinomas
    tumoral     --over  
    in non-small cell lung cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target BAG3 induction might represents as an unwanted molecular consequence of utilizing proteasome inhibitors to combat tumors
    SystemTypeDisorderPubmed
    tumor  
    BAG3 induction might represents as an unwanted molecular consequence of utilizing proteasome inhibitors to combat tumors
    cancerhemopathy 
    may be a potential therapeutic target for lymphocytic leukemia
    ANIMAL & CELL MODELS