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PROSITE documentation PDOC51035BAG domain profile
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PURL: https://purl.expasy.org/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 [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.
Last update:November 2004 / First entry.
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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). | |
| PubMed ID | 12406544 |
| 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. | |
| Source | Cell 80:279-284(1995). | |
| PubMed ID | 7834747 |
| 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. | |
| Source | Science 291:1553-1557(2001). | |
| PubMed ID | 11222862 | |
| DOI | 10.1126/science.291.5508.1553 |
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