CALR3 Human

Calreticulin 3 can be divided into three distinct domains:

1. N-terminal globular domain: This domain is involved in binding to misfolded proteins and other chaperones.
2. Proline-rich P-domain: This elongated arm-like structure is essential for binding to other ER-resident proteins.
3. C-terminal acidic domain: This domain is responsible for calcium binding and storage .

Calreticulin 3 functions as a lectin-independent chaperone, meaning it does not rely on carbohydrate recognition to assist in protein folding. Instead, it interacts with specific client proteins, such as ADAM3, during the spermatogenesis process .

Calreticulin 3 is involved in various biological processes, including:

• Protein folding: Ensuring that newly synthesized proteins attain their correct three-dimensional structures.
• Calcium homeostasis: Regulating intracellular calcium levels, which is vital for numerous cellular functions.
• MHC class I antigen processing: Assisting in the presentation of antigens on the cell surface, which is crucial for immune responses .

Mutations in the CALR3 gene have been linked to familial hypertrophic cardiomyopathy type 19 (CMH19), a hereditary heart disorder characterized by ventricular hypertrophy. Symptoms of this condition include dyspnea, syncope, collapse, palpitations, and chest pain .

Recombinant human calreticulin 3 is produced using various expression systems, including yeast and bacterial hosts. The recombinant protein is typically purified to high levels of purity and retains its functional integrity, making it suitable for research and potential therapeutic applications .

In yeast expression systems, such as Saccharomyces cerevisiae and Pichia pastoris, the full-length human calreticulin precursor, including its native signal sequence, is expressed and secreted into the culture medium. The recombinant protein produced in these systems is structurally and functionally identical to the native protein, ensuring its biological activity .