{PDOC50156}
{PS50156; SSD}
{BEGIN}
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* Sterol-sensing domain (SSD) profile *
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The sterol-sensing domain (SSD) is an around 180 residues long cluster of five
membrane-spanning segments.  The  SSD  domain  is  conserved  across phyla and
confers sensitivity  to  regulation by sterol. Although the SSD domain appears
to function as a regulatory domain involved in linking vesicle trafficking and
protein localization  with  such  varied processes as cholesterol homeostasis,
cell signalling  and cytokinesis, its exact mode of action is not clear. It is
not known  whether  it interacts with sterols, such as cholesterol, or whether
it interacts with another-sterol regulated protein. Alternatively, the SSD may
interact with lipids other than cholesterol [1,2,3].

Some proteins known to contain a SSD are listed below:

 - Patched  from  Drosophila.  It  is  receptor  for the cholesterol-activated
   protein sonic hedghog.
 - 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR).
 - Sterol   regulatory  element  binding-protein  cleavage-activating  protein
   (SCAP).
 - The  Niemann-Pick  type  C  (NPC1)  protein  [4].  It  is  involved  in the
   intracellular trafficking of cholesterol.

In addition  to  the  proteins  above,  the  SSD  is also found in a number of
bacterial drug resistance proteins.

The profile we developed covers the entire SSD domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2002 / Text revised.

[ 1] Nohturfft A., Brown M.S., Goldstein J.L.
     "Topology of SREBP cleavage-activating protein, a polytopic membrane
     protein with a sterol-sensing domain."
     J. Biol. Chem. 273:17243-17250(1998).
     PubMed=9642295
[ 2] Davies J.P., Ioannou Y.A.
     "Topological analysis of Niemann-Pick C1 protein reveals that the
     membrane orientation of the putative sterol-sensing domain is
     identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and
     sterol regulatory element binding protein cleavage-activating
     protein."
     J. Biol. Chem. 275:24367-24374(2000).
     PubMed=10821832; DOI=10.1074/jbc.M002184200
[ 3] Kuwabara P.E., Labouesse M.
     "The sterol-sensing domain: multiple families, a unique role?"
     Trends Genet. 18:193-201(2002).
     PubMed=11932020
[ 4] Loftus S.K., Morris J.A., Carstea E.D., Gu J.Z., Cummings C.,
     Brown A., Ellison J., Ohno K., Rosenfeld M.A., Tagle D.A.,
     Pentchev P.G., Pavan W.J.
     "Murine model of Niemann-Pick C disease: mutation in a cholesterol
     homeostasis gene."
     Science 277:232-235(1997).
     PubMed=9211850

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