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Beschreibung

InsP3R3, IP3 receptor isoform 3, IP3R 3, Type 3 inositol 1,4,5-trisphosphate receptor, Type 3 InsP3 receptor) is encoded by the ITPR3 gene (Gene ID 3710) in human. The inositol 1,4,5-trisphosphate (InsP3) receptors, InsP3R1, InsP3R2, and InsP3R3, play an important role in maintaining normal epithelial secretory function by mediating intracellular Ca2+ release. InsP3R3 is the major isoform in hepatic bile ducts, where it is concentrated along the subapical portion of the ER and regulates bicarbonate (HCO3 ) and chloride (Cl ) secretion into the bile. Wherease hepatocytes express mainly InsP3R2 that is involved in modulating the secretion of bile solutes. A loss of InsP3R3 expression in cholangiocytes is found in primary biliary cirrhosis (PBC), an autoimmune liver disease characterized by the loss of bile ducts and impaired bile secretion. Likewise, InsP3R3 and InsP3R2 double knockout mice are reported to exhibit severe defects of pancreatic zymogen secretion. Human InsP3R3 is a 6-transmembrane (a.a. 2203-2223, 2236-2256, 2265-2285, 2326-2346, 2369-2389, 2497-2517) ER membrane protein, having both its N- and C-terminal ends (a.a. 1-2202 and 2518-2671) exposed at the cytoplasmic side. The N-terminal cytoplasmic region contains five MIR (Mannosyltransferase, InsP3R, RyR) domains (a.a. 113-173, 174-224, 232-288, 295-372, 378-434) and the InsP3-binding sites (a.a. 266-270, 507-510, 567-569).