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.