Figure 2. PTH and PTHR gene families: PTHrP, PTH and TIP39 appear to be members of a single gene family. Although only nine amino acids in the NH2-terminal domains of these three peptides are conserved, these are functionally important residues. The receptors for these peptides, PTH1R and PTH2R, are both 7 transmembrane-spanning G protein-coupled receptors which seem to be members of a single gene family. PTHrP binds and activates PTH1R; it binds weakly to PTH2R and does not activate it. PTH can bind and activate both PTH1R and PTH2R. TIP39 can bind to and activate PTH2R but not PTH1R.