|PROSITE documentation PDOC51035|
Bcl2-associated athanogene (BAG) family proteins participate in a wide variety of cellular processes including cell survival (stress response), proliferation, migration and apoptosis. These proteins share a conserved region of about 110 amino-acids at their carboxy terminus, named as the BAG domain. It has been shown [1,3] that the BAG domain can interact with the heat shock proteins 70 (Hsc70/Hsp70) (see <PDOC00269>) and can modulate either positively or negatively these chaperone proteins. In BAG-1, the BAG domain also interact with the serine/threonine kinase Raf-1 in a mutually exclusive interaction. BAG-1 promotes cell growth by binding to and stimulating Raf-1 activity. The binding to Hsc70/Hsp70 have an anti-apoptotic effect, it diminishes Raf-1 signaling and inhibits subsequent events, such as DNA synthesis and arrests of the cell cycle . The C-terminus of the BAG domain is also a possible site of interaction with Bcl-2 in BAG-1 and BAG-3/CAIR-1 which provides a supra-additive anti-apoptotic effect .
The BAG domain is found in association with several N-terminal domains like ubiquitin (see <PDOC00271>), IQ (see <PDOC50096>), and the WW domain (see <PDOC50020>). These domains enable BAG family proteins to interact with other proteins and potentially alter the activity of those target proteins by recruiting Hsc70/Hsp70 .
The crystal structure of the BAG domain has been solved (see <PDB:1HX1>), and revealed that it consists of three anti-parallel α helices. In the BAG domain the first and the second α-helices interact with the serine/threonine kinase Raf-1 and the second and third α-helices interact with the ATP-binding pocket of Hsc70/Hsp70.
The profile we developed covers half of the first α-helix, the second one and the third one.Last update:
November 2004 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Doong H. Vrailas A. Kohn E.C.|
|Title||What's in the 'BAG'? -- a functional domain analysis of the BAG-family proteins.|
|Source||Cancer Lett. 188:25-32(2002).|
|2||Authors||Takayama S. Sato T. Krajewski S. Kochel K. Irie S. Millan J.A. Reed J.C.|
|Title||Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity.|
|3||Authors||Sondermann H. Scheufler C. Schneider C. Hoehfeld J. Hartl F.-U. Moarefi I.|
|Title||Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors.|