{PDOC51035}
{PS51035; BAG}
{BEGIN}
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* BAG domain profile *
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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 alpha helices. In the BAG
domain   the   first   and   the   second   alpha-helices  interact  with  the
serine/threonine  kinase Raf-1 and the second and third alpha-helices interact
with the ATP-binding pocket of Hsc70/Hsp70.

The  profile we developed covers half of the first alpha-helix, the second one
and the third one.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: November 2004 / First entry.

[ 1] Doong H., Vrailas A., Kohn E.C.
     "What's in the 'BAG'? -- a functional domain analysis of the BAG-family
     proteins."
     Cancer Lett. 188:25-32(2002).
     PubMed=12406544
[ 2] Takayama S., Sato T., Krajewski S., Kochel K., Irie S., Millan J.A.,
     Reed J.C.
     "Cloning and functional analysis of BAG-1: a novel Bcl-2-binding
     protein with anti-cell death activity."
     Cell 80:279-284(1995).
     PubMed=7834747
[ 3] Sondermann H., Scheufler C., Schneider C., Hoehfeld J., Hartl F.-U.,
     Moarefi I.
     "Structure of a Bag/Hsc70 complex: convergent functional evolution of
     Hsp70 nucleotide exchange factors."
     Science 291:1553-1557(2001).
     PubMed=11222862; DOI=10.1126/science.291.5508.1553

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