Calreticulin: Proteins and Enzymes

Calreticulin is a multifunctional, intracellular calcium-binding protein that is found in most eukaryotic cells. It serves as a key regulator of intracellular free calcium levels. Calreticulin also functions as a lectin-type chaperone in the endoplasmic reticulum (ER). It binds to oligosaccharide residues on newly synthesized glycoproteins to ensure proper folding and retains non-native protein conformers within the ER where they are targeted for degradation. Calreticulin has also been characterized as an inhibitor of steroid hormone-regulated gene expression. Its N-terminal domain, which is termed Vasostatin, binds to the KxFFKR motif located in the DNA-binding domain of nuclear hormone receptors, preventing the receptors from binding to their specific recognition sequence. Additionally, Calreticulin is thought to function as an extracellular lectin and an intracellular mediator of integrin-dependent cell adhesion. Calreticulin-2, an isoform of calreticulin, is expressed in testis, while calreticulin is expressed more widely. The two isoforms of human calreticulin share 53% sequence identity.