PROSITE documentation PDOC00636

Calreticulin family signatures

Calreticulin [1] (also known as calregulin, CRP55 or HACBP) 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:

 a) An N-terminal, probably globular, domain  of about 180 amino acid residues
    (N-domain);
 b) 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;
 c) 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 evolutionary related to the following proteins:

• Onchocerca volvulus antigen RAL-1. RAL-1 is highly similar to calreticulin, but possesses a C-terminal domain rich in lysine and arginine and lacks acidic residues and is therefore not expected to bind calcium in that region.
• Calnexin [2]. A calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins.
• Calmegin [3] (or calnexin-T), a testis-specific calcium-binding protein highly similar to calnexin.

We developed three signature patterns for this family of proteins. The first two patterns are based on conserved regions in the N-domain; the third pattern corresponds to positions 4 to 16 of the repeated motif in the P-domain.