Coevolution of the Relaxin‐Like Peptides and Their Receptors

Currently, four relaxin peptide family receptors are known: LGR7 is the relaxin receptor, although it also interacts specifically with relaxin-3; LGR8 is the insulin-like factor 3 (INSL3) receptor; and GPCR135 or the somatostatin- and angiotensin-like peptide receptor (SALPR) and GPCR142 are both specific relaxin-3 receptors. Because these receptors coevolved together with their relaxin ligands, phylogenetic analysis of these sequences can provide insight into peptide-receptor interactions and even predict interacting partners for INSL4, INSL5, and INSL6, the receptors for which are unknown.