{PDOC50869}
{PS50869; BRICHOS}
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* BRICHOS domain profile *
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BRICHOS is a domain of ~100 amino acids, which is found in proteins associated
with dementia,  respiratory distress and cancer. In several of these proteins,
the BRICHOS  domain  is located in the propeptide region that is removed after
proteolytic processing.   The   common  presence  of  the  BRICHOS  domain  in
Caenorhabditis elegans  and Drosophila melanogaster suggests an ancient origin
close to  the  appearance  of  animals.  Based on the common properties of the
proteins containing  BRICHOS  domains,  three  possible  functions  have  been
proposed: (1)  BRICHOS  could  aid  targeting  to  the  secretory pathway; (2)
BRICHOS might assist the specialized intracellular protease processing system;
and (3)   BRICHOS   might  have  an  intramolecular  chaperone-like  function,
protecting and  avoiding peptide aggregation of the cysteine-rich C-termini of
ChM-I, ITM2B and CA11, or of the highly hydrophobic N-terminal region of SP-C,
which are  capable  of  conformational  change  (alpha  helix  to  beta  sheet
aggregates) producing amyloid fibrils [1].

The BRICHOS  domain  includes  a  pair  of  conserved  cysteine  residues that
probably form  a  disulfide bridge. The blocks of sequence conservation of the
BRICHOS domain are predominantly located around these cysteines. Of particular
interest is  the Asp and Phe or Tyr pair, whose complete conservation suggests
a possible functional importance [1].

Some proteins known to include a BRICHOS domain are listed below:

 - Proteins of the integral membrane protein (ITM2 or BRI) 2 family. In human,
   defects in  ITM2B  are associated with familial British and Danish dementia
   (FBD and FDD).
 - Proteins  of  the  chondromodulin-I (ChM-I) family. Chondrosarcoma has been
   shown  to be related to the downregulation of ChM-I.
 - CA11 protein. It is downregulated in stomach cancer.
 - Pulmonary  surfactant-associated  protein  C  (SP-C).  Deficiencies  of the
   pulmonary surfactant  caused by premature birth, or surfactant inactivation
   from lung injury, can result in lethal respiratory distress syndrome (RDS).

The profile we developed covers the entire BRICHOS domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 2003 / First entry.

[ 1] Sanchez-Pulido L., Devos D., Valencia A.
     "BRICHOS: a conserved domain in proteins associated with dementia,
     respiratory distress and cancer."
     Trends Biochem. Sci. 27:329-332(2002).
     PubMed=12114016;

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