Calreticulin is a multifunctional, highly conserved Ca2+ -binding protein that is localized to the endoplasmic reticulum (ER), but has also been detected in the nucleus and nuclear envelop. Like many other ER proteins, it has the conserved ER retention KDEL (Lys-Asp-Glu-Leu) sequence at its C-terminus (1-3). CRT’s three domains include a 180 residue N-terminal domain, a proline-rich P-domain (residues 189-288) that binds Ca2+ with high affinity and shares homology with calnexin (CNX) and calmegin, and a 110 residue C-terminal domain that binds Ca2+ with low affinity but high capacity (1,3). Recent studies suggest that this soluble ER protein has a multifunctional role. It appears to be involved in calcium storage and regulation as well as having a molecular
chaperone activity. It has been shown to interact with the cytoskeleton and to be involved in the regulation of gene expression. Calreticulin may also play a role in cellular proliferation including its apparent activity in the proliferation of certain viruses within mammalian host cells (4, 5), and it has also been shown to be induced in response to various types of cell stress including amino acid deprivation (6). Close interconnections among protein synthesis, gene expression and calcium signaling have been observed by many researchers in recent years. Calreticulin might be centrally located and therefore it crucially participates in the coordination of many functions by the cell (4, 5). Studies also suggest its involvement in a few diseases such as systemic lupus erythematosus, rheumatoid arthritis, celiac disease, complete congenital heart block, and halothane hepatitis (1).