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FLASH GENE

Symbol

BAG3

contributors: mct - updated : 17-02-2014

HGNC name	BCL2-associated athanogene 3
HGNC id	939

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed tumor     BAG3 induction might represents as an unwanted molecular consequence of utilizing proteasome inhibitors to combat tumors cancer hemopathy   may be a potential therapeutic target for lymphocytic leukemia

ANIMAL & CELL MODELS