{PDOC50197}
{PS50197; BEACH}
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* BEACH domain profile *
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The BEACH (for BEIge And CHS) domain is a region of about 300 residues that is
highly conserved  in  a  large  family  of  eukaryotic  proteins.  Many of the
proteins that  contain a BEACH domain are very large (with >2000 residues) and
have putative functions in vesicular transport, membrane dynamics and receptor
signaling. The  BEACH  domain  is  crucial  for  the  normal function of these
proteins. In  all known BEACH-containing proteins, the BEACH domain is located
just prior  to a WD-40 domain (see <PDOC00574>) in the primary sequence, which
is located  at  the extreme C-terminus of most of these proteins. In addition,
structural analysis  revealed  that  BEACH domain has intimate contacts with a
fold identical to that of PH domains (see <PDOC50003>) just prior to it in the
primary sequence. Consistent with the structural analysis, biochemical studies
show that  the  PH and BEACH domains have strong interactions, suggesting they
may function  as  a  single  unit. The function of the BEACH domain is unknown
[1,2,3].

The resolution of the crystal structure of the BEACH domain of human Nbea (see
<PDB:1MI1>) as  shown that it has a new and unusual polypeptide backbone fold,
as the peptide segments in its core do not assume regular secondary structures
(alpha-helix or beta-sheet). In addition, only a few main-chain hydrogen-bonds
are made among these segments. The structure of the BEACH domain also contains
11 alpha-helices that are arranged on the periphery of the structure, but help
to enclose the core of the domain [3].

Proteins known to contain a BEACH domain are listed below:

 - Human  lysosomal  trafficking  regulator  or Chediak-Higashi Syndrome (CHS)
   protein. Defects  in  the  CHS  protein  are  the  cause of Chediak-Higashi
   Syndrome, a  rare  autosomal  disorder  characterized  by hypopigmentation,
   severe immunologic   deficiency,   a   bleeding   tendency  and  neurologic
   abnormalities. As an important hallmark of several tissues derived from CHS
   patients is  the  occurrence  of  giant inclusion bodies and organelles and
   protein sorting  defects in these organelles, the CHS protein is thought to
   be involved  in  vesicle  fusion or fission. The CHS protein contains 7 WD-
   repeats. The mouse ortholog of CHS is called 'beige'.
 - Mammalian FAN (Factor Associated with Neutral-sphingomyelinase activation).
   It binds to the N-SMase activation domain (NSD) of the p55 TNF-receptor and
   mediates the  activation of N-SMase after ligand binding. FAN contains five
   WD-repeats.
 - Human  lipopolysaccharide-responsive  and  beige-like  anchor protein (LBA)
   (also known  as  Beige  like  protein  or CDC4-like protein). It may have a
   function in  in polarized vesicle trafficking, and is localized to vesicles
   after stimulation by lipopolysaccharide (LPS).
 - Vertebrate  neurobeachin (Nbea). It has been implicated in membrane traffic
   in neuronal cells.
 - Caenorhabditis elegans hypothetical proteins F52C9.2 and F52C9.3.
 - Yeast hypothetical protein YCR032W.

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

[ 1] Nagle D.L., Karim M.A., Woolf E.A., Holmgren L., Bork P., Misumi D.J.,
     McGrail S.H., Dussault B.J. Jr., Perou C.M., Boissy R.E., Duyk G.M.,
     Spritz R.A., Moore K.J.
     "Identification and mutation analysis of the complete gene for
     Chediak-Higashi syndrome."
     Nat. Genet. 14:307-311(1996).
     PubMed=8896560; DOI=10.1038/ng1196-307
[ 2] Adam-Klages S., Schwandner R., Adam D., Kreder D., Bernardo K.,
     Kronke M.
     "Distinct adapter proteins mediate acid versus neutral
     sphingomyelinase activation through the p55 receptor for tumor
     necrosis factor."
     J. Leukoc. Biol. 63:678-682(1998).
     PubMed=9620659
[ 3] Jogl G., Shen Y., Gebauer D., Li J., Wiegmann K., Kashkar H.,
     Kronke M., Tong L.
     "Crystal structure of the BEACH domain reveals an unusual fold and
     extensive association with a novel PH domain."
     EMBO J. 21:4785-4795(2002).
     PubMed=12234919

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