PROSITE documentation PDOC51035

BAG domain profile

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 [1]. 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 [2].

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 [1].

The crystal structure of the BAG domain has been solved (see <PDB:1HX1>)[3], 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.