Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol BAG3 contributors: mct - updated : 17-02-2014
HGNC name BCL2-associated athanogene 3
HGNC id 939
Corresponding disease
CMD1HH cardiomyopathy, dilated 1 HH
MFMB myofibrillar myopathy, BAG3-related
Location 10q26.11      Physical location : 121.410.881 - 121.437.327
Synonym name
  • Bcl-2-binding protein
  • docking protein CAIR-1
  • BAG-family molecular chaperone regulator-3
  • Synonym symbol(s) BIS, BAG-3, CAIR-1, MGC104307
    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
    Physical map
    LOC387713 10 similar to ventral anterior homeobox 1 TRIK 10q26.12 TWIK-related spinal cord K+ channe SLC18A2 10q25 solute carrier family 18 (vesicular monoamine), member 2 LOC118987 10q26.12 hypothetical protein LOC118987 LOC387714 10 LOC387714 EMX2 10q26.1 empty spiracles homolog 2 (Drosophila) Rab11-FIP2 10q26.12 KIAA0941 protein C10orf5 10q26.12 chromosome 10 open reading frame 5 FLJ13188 10q26.12 hypothetical protein FLJ13188 GPR10 10q25.3-q26 G protein-coupled receptor 10 LOC390007 10 similar to Mitochondrial import receptor subunit TOM22 homolog (Translocase of outer membrane 22 kDa subunit homolog) (hTom22) (1C9-2) C10orf46 10q26.12-q26.13 chromosome 10 open reading frame 46 LOC88066 10q26.13 similar to 60S ribosomal protein L17 (L23) NANOS1 10q26.13 nanos homolog 1 (Drosophila) EIF3S10 10q26 eukaryotic translation initiation factor 3, subunit 10 theta, 150/170kDa SFXN4 10q26.12 sideroflexin 4 PRDX3 10q25-q26 peroxiredoxin 3 GPRK5 10q24-qter G protein-coupled receptor kinase 5 RGS10 10q25 regulator of G-protein signalling 10 TIAL1 10q26.11 TIA1 cytotoxic granule-associated RNA binding protein-like 1 LOC119563 10q26.13 similar to 40S ribosomal protein S8 BAG3 10q25.2-q26.2 BCL2-associated athanogene 3 LOC93202 10q26.13 thioredoxin 1 pseudogene 2 INPP5F 10q26.13 inositol polyphosphate-5-phosphatase F FLJ13081 10q26.13 hypothetical protein FLJ13081 SEC23IP 10q25-q26 SEC23 interacting protein LOC338570 10q26.13 similar to alpha NAC/1.9.2. protein LOC196051 10q26.13 hypothetical protein LOC196051 WDR11 10q26 WD repeat domain 11 FGFR2 10q26 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) ATE1 10q26.13 arginyltransferase 1 FLJ20003 10q26.13 hypothetical protein FLJ20003
    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