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Acts by binding and activating the G protein-coupled receptor PTH1R, engaging the receptor to activate G(s)-mediated cAMP/PKA signaling and G(q)-mediated PLC/PKC signaling (PubMed:18375760, PubMed:35932760). In bone, acts indirectly on osteoclasts by binding PTH1R on cells of the osteoblast/osteocyte lineage, where it increases expression of TNFSF11/RANKL and decreases expression of TNFRSF11B/OPG, thereby raising the RANKL/OPG ratio and stimulating osteoclast differentiation and bone resorption (PubMed:9797718, PubMed:11454517). Stimulates also [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells (PubMed:21076856). In distal renal tubule cells, stimulates active Ca(2+) reabsorption via the adenylyl cyclase-cAMP-protein kinase A (PKA) pathway leading to the phosphorylation and activation of the calcium selective cation channel TRPV5 (PubMed:19423690). Acting on PTH1R in proximal renal tubule cells, decreases reabsorption of filtered phosphate by reducing apical abundance of SLC34A1, through a mechanism involving PTH1R-activated PKC-mediated phosphorylation of the scaffold NHERF1, causing dissociation of the NHERF1-SLC34A1 complex and subsequent clathrin-mediated endocytosis and lysosomal degradation of the cotransporter (By similarity). Activates also transcription of CYP27B1 (25-hydroxyvitamin D3 1-alpha-hydroxylase) through a cAMP/PKA/SIK2-SIK3/CRTC2 axis, thereby increasing renal synthesis of the active vitamin D metabolite 1,25-dihydroxyvitamin D(3) (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18375760"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35932760"}],"value":"Interacts with PTH1R (via N-terminal extracellular domain)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P01270","intActId":"EBI-716817"},"interactantTwo":{"uniProtKBAccession":"Q12797-6","geneName":"ASPH","intActId":"EBI-12092171"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P01270","intActId":"EBI-716817"},"interactantTwo":{"uniProtKBAccession":"Q03431","geneName":"PTH1R","intActId":"EBI-2860297"},"numberOfExperiments":6,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"4509319"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7829495"}],"value":"Secreted","id":"SL-0243"}}]},{"commentType":"DISEASE","disease":{"diseaseId":"Hypoparathyroidism, familial isolated, 1","diseaseAccession":"DI-01590","acronym":"FIH1","description":"A form of hypoparathyroidism, a disorder characterized by hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone. 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