InterPro domain: IPR009169

Calreticulin is a ubiquitous protein found in a wide range of species and in all nucleated cell types. It is an ancient and highly conserved protein with an exceptionally wide scope and variety of functions. Initially known as the high-affinity calcium-binding endoplasmic reticulum (ER) and sarcoplamic reticulum (SR) protein "calregulin", calreticulin is now known to associate with proteins in the cytoplasm, nucleus and extracellular compartment.

Calreticulin is a major Ca ² -binding/storage chaperone residing in the ER lumen [ 1 ]. Molecular chaperones residing in the ER facilitate the folding and prevent the aggregation of newly synthesized proteins. Interaction between the molecular chaperone and the misfolded protein leads to the retention, retranslocation and eventual degradation of the misfolded protein by the proteasome after ubiquitination [ 2 ]. Calreticulin binds (buffers) Ca ² with high capacity and participates in folding newly synthesized proteins and glycoproteins. It is an important component of the calreticulin/calnexin cycle and quality control pathways in the ER [ 3 ]. Studies on calreticulin-deficient and calreticulin-transgenic mice revealed that calreticulin is a new cardiac embryonic gene and is essential during cardiac development [ 3 , 4 ]. Calreticulin has also been characterised as an extracellular lectin, an intracellular mediator of integrin-mediated cell adhesion, an inhibitor of steroid hormone-regulated gene expression and a C1q-binding protein [ 5 ].

A proposed model of calreticulin domains includes a globular N-domain, a central proline-rich P-domain and an acidic C-domain. A detailed structure of the central P-domain was revealed by NMR studies, while a model of the globular N-domain of calreticulin is based on crystallographic data reported for the highly similar calnexin [ 6 ].

Calreticulin is also known as calregulin, Erp60, CRP55, CAB-63 and CaBP3 [ 7 ].

1. Calreticulin in cardiac development and pathology. Biochim. Biophys. Acta 1600, 32-7
2. ER quality control: the cytoplasmic connection. Cell 88, 427-30
3. Calreticulin is essential for cardiac development. J. Cell Biol. 144, 857-68
4. Complete heart block and sudden death in mice overexpressing calreticulin. J. Clin. Invest. 107, 1245-53
5. Calreticulin. Int. J. Biochem. Cell Biol. 30, 553-8
6. NMR structure of the calreticulin P-domain. Proc. Natl. Acad. Sci. U.S.A. 98, 3133-8
7. Calreticulin. Biochem. J. 285 ( Pt 3), 681-92