Human Relaxin 3 (H3 relaxin, INSL7) is one of seven relaxin-like peptides belonging to the insulin superfamily. Unlike human relaxins 1 and 2, it does not play a role in reproduction but appears to be a neuropeptide involved in stress response in the brain stem. The 142aa Relaxin 3 pre-proprotein is processed to remove a 25aa signal peptide and a connecting peptide (aa53-118). The resulting mature Relaxin 3 is a 5.5kD, 51aa secreted heterodimer of A (aa119-142) and B (aa26-52) peptides connected by two intermolecular disulfide bonds. Relaxin 3 is the only known ligand for the G-protein-coupled receptor RXFP3. In rodents, GPCR135 is expressed primarily in the supraoptic and paraventricular nucleus. This region has connections to the dorsal tegmental region of the pons (also called the nucleus incertus), where expression of Relaxin 3 is highest. Relaxin 3 also binds the more widely expressed LGR7 (RXFP1) receptor, but with lower affinity than that of Relaxin 2. Although binding of Relaxin 3 to LGR7 increases intracellular cAMP, binding to GPCR135 inhibits cAMP accumulation, indicating coupling to Gi, Go or Gz by this receptor. Relaxin 3 expression does not overlap well with its other receptor, GPCR142, which instead appears to be the primary receptor for INSL5.