Three subtypes of IP3Rs, derived from three distinct genes, have been identified in mammals. All three receptors have six transmembrane domains and a pore domain between TM5 and TM6. The N-terminus as well as the C-terminus are cytoplasmic. Each IP3R consists of an N-terminal ligand binding domain (LBD) and a C-terminal domain which is linked by a long regulatory domain. The C-terminus is constitutively active, suggesting that the regulatory domain is required to maintain the suppression of channel activity. n Type 2 IP3R (IP3R2) is expressed in various tissues and cell lines. IP3R2 mRNA is localized in the intralobular duct cells of the submandibular gland, the urinary tubule cells of the kidney, the epithelial cells of epididymal ducts and the follicular granulosa cells of the ovary5. IP3R2 is active during osteoclast differentiation, and its absence causes a partial defect in osteoclastic differentiation.
