PROSITE documentation PDOC50869

BRICHOS domain profile

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 (α helix to β 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.