During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3. Required for sperm fertility (By similarity). CALR3 capacity for calcium-binding may be absent or much lower than that of CALR.

Testis specific.

Defects in CALR3 are the cause of familial hypertrophic cardiomyopathy type 19 (CMH19) [MIM:613875]. CMH19 is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.

Belongs to the calreticulin family.

Can be divided into a N-terminal globular domain, a proline-rich P-domain forming an elongated arm-like structure and a C-terminal acidic domain. The P-domain binds one molecule of calcium with high affinity, whereas the acidic C-domain binds multiple calcium ions with low affinity.
The interaction with glycans occurs through a binding site in the globular lectin domain.
The zinc binding sites are localized to the N-domain.

Endoplasmic reticulum lumen.