Recombinant Human PTH1R/PTHR1 Protein, CF

PTH1R (parathyroid receptor-1, also called PTHR1) is an 85-95 kDa member of the G-protein coupled receptor family 2 that is a critical receptor regulating Ca⁺⁺ homeostasis (1-5). The human PTH1R cDNA encodes 593 amino acids (aa) including a 26 aa signal sequence and a long extracellular domain (aa 27-189) that contains the PTH (parathyroid hormone) and PTHrP (PTH-related protein) docking site (aa 173-189), followed by seven transmembrane domains within the C-terminal 404 aa (2-4). Within the N-terminal ECD, human PTH1R shares 87%, 88%, 96%, 94% and 93% aa identity with mouse, rat, canine, bovine and porcine PTH1R, respectively. PTH of other mammals will bind and stimulate human PTH1R, although with differing affinities (2). PTH1R is mainly expressed in bone and kidney, but is also present on hepatocytes, smooth muscle cells, and in other tissues where PTH and PTHrP are found (1-3, 5, 6). Through PTH1R on osteoblasts, PTH promotes differentiation of osteoclasts, which in turn promote release of Ca⁺⁺ from bone (1, 5). PTH1R on osteocytes, however, allows PTH to promote bone formation (7). In renal epithelium, it promotes conversion of Vitamin D to its active form, lowers Ca⁺⁺ excretion and increases phosphate excretion (1, 5). Following PTH binding, PTH1R undergoes a conformation change which activates cAMP, IP3, PKC and Ca⁺⁺ signaling pathways (1, 8). PTH1R is then phosphorylated and downregulated by internalization (9). Dwarfism in Jansen‑type metaphyseal chondrodysplasia is associated with PTH1R gain of function, while in Blomstrand chondrodysplasia, PTH1R function is lost (10, 11). Impaired PTH1R function may be a factor in developmental endochondromas in Ollier disease (12). Polymorphisms may also be associated with variation in bone mineral density (13).