Calreticulin (IPR009169)

Short name: Calreticulin

Overlapping homologous superfamilies

Family relationships


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 Ca2 -binding/storage chaperone residing in the ER lumen [PMID: 12445456]. 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 [PMID: 9038332]. Calreticulin binds (buffers) Ca2 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 [PMID: 9038332]. Studies on calreticulin-deficient and calreticulin-transgenic mice revealed that calreticulin is a new cardiac embryonic gene and is essential during cardiac development [PMID: 10085286, PMID: 11375414]. 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 [PMID: 9693955].

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 [PMID: 11248044].

Calreticulin is also known as calregulin, Erp60, CRP55, CAB-63 and CaBP3 [PMID: 1497605].

GO terms

Biological Process

GO:0006457 protein folding

Molecular Function

GO:0005509 calcium ion binding
GO:0051082 unfolded protein binding

Cellular Component

GO:0005783 endoplasmic reticulum

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.