The BRICHOS domain is about 100 amino acids long. It is found in a variety of proteins implicated in dementia, respiratory distress and cancer. Its exact function is unknown; roles that have been proposed for it include (a) in targeting of the protein to the secretory pathway, (b) intramolecular chaperone-like function, and (c) assisting the specialised intracellular protease processing system (PUBMED:12114016). This C-terminal domain is embedded in the endoplasmic reticulum lumen, and binds to the N-terminal, transmembrane, SP_C, PF08999 provided that it is in non-helical conformation. Thus the Brichos domain of proSP-C is a chaperone that induces alpha-helix formation of an aggregation-prone TM region (PUBMED:19472327) .
The BRICHOS domain is found in a variety of proteins implicated in dementia, respiratory distress and cancer, including BRI-2, chondromodulin-I (ChM-I), CA11, and surfactant protein C [ (PUBMED:12114016) ]. Its exact function is unknown; roles that have been proposed for it include (a) targeting the protein to the secretory pathway, (b) an intramolecular chaperone-like function, and (c) assisting the specialised intracellular protease processing system [ (PUBMED:12114016) ].
Family alignment:
There are 3414 BRICHOS domains in 3356 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing BRICHOS domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with BRICHOS domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing BRICHOS domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
The Brichos domain of prosurfactant protein C can hold and fold atransmembrane segment.
Protein Sci. 2009; 18: 1175-82
Display abstract
Prosurfactant protein C (proSP-C) is a 197-residue integral membraneprotein, in which the C-terminal domain (CTC, positions 59-197) islocalized in the endoplasmic reticulum (ER) lumen and contains a Brichosdomain (positions 94-197). Mature SP-C corresponds largely to thetransmembrane (TM) region of proSP-C. CTC binds to SP-C, provided that itis in nonhelical conformation, and can prevent formation of intracellularamyloid-like inclusions of proSP-C that harbor mutations linked tointerstitial lung disease (ILD). Herein it is shown that expression ofproSP-C (1-58), that is, the N-terminal propeptide and the TM region, inHEK293 cells results in virtually no detectable protein, whilecoexpression of CTC in trans yields SDS-soluble monomeric proSP-C (1-58).Recombinant human (rh) CTC binds to cellulose-bound peptides derived fromthe nonpolar TM region, but not the polar cytosolic part, of proSP-C, andrequires >/=5-residues for maximal binding. Binding of rhCTC to anonhelical peptide derived from SP-C results in alpha-helix formationprovided that it contains a long TM segment. Finally, rhCTC and rhCTCBrichos domain shows very similar substrate specificities, butrhCTC(L188Q), a mutation linked to ILD is unable to bind all peptidesanalyzed. These data indicate that the Brichos domain of proSP-C is achaperone that induces alpha-helix formation of an aggregation-prone TMregion.
BRICHOS: a conserved domain in proteins associated with dementia,respiratory distress and cancer.
Trends Biochem Sci. 2002; 27: 329-32
Display abstract
A novel domain (the BRICHOS domain) of approximately 100 amino acids hasbeen identified in several previously unrelated proteins that are linkedto major diseases. These include BRI(2), which is related to familialBritish and Danish dementia (FBD and FDD); Chondromodulin-I (ChM-I),related to chondrosarcoma; CA11, related to stomach cancer; and surfactantprotein C (SP-C), related to respiratory distress syndrome (RDS). Inseveral of these, the conserved BRICHOS domain is located in thepropeptide region that is removed after proteolytic processing.Experimental data suggest that the role of this domain could be related tothe complex post-translational processing of these proteins.
