InterPro domain: IPR001580

The calreticulin family is a family of calcium-binding ER chaperonesthat includes calreticulin, calnexin and camlegin [ 1 ].

Calreticulin (calregulin) [ 2 ] is a high-capacity calcium-binding protein which is present in most tissues and located at the periphery of the endoplasmic (ER) and the sarcoplamic reticulum (SR) membranes. It probably plays a role in the storage of calcium in the lumen of the ER and SR and it may well have other important functions.

Structurally, calreticulin is a protein of about 400 amino acid residues consisting of three domains:

• An N-terminal, probably globular, domain of about 180 amino acid residues (N-domain).
• A central domain of about 70 residues (P-domain) which contains three repeats of an acidic 17 amino acid motif. This region binds calcium with a low-capacity, but a high-affinity.
• A C-terminal domain rich in acidic residues and in lysine (C-domain). This region binds calcium with a high-capacity but a low-affinity.

Calreticulin is evolutionarily related to several other calcium-binding proteins, including Onchocerca volvulus antigen RAL-1, calnexin [ 3 ] and calmegin [ 4 ].

1. Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. Biochem. J. 370, 449-58
2. Calreticulin. Biochem. J. 285 ( Pt 3), 681-92
3. Calnexin: a membrane-bound chaperone of the endoplasmic reticulum. Trends Biochem. Sci. 19, 124-8
4. Molecular cloning of a novel Ca(2+)-binding protein (calmegin) specifically expressed during male meiotic germ cell development. J. Biol. Chem. 269, 7744-9