A gene on chromosome 4q31 encodes a 381 amino acid protein, NPY2-R(also designated Neuropeptide Y receptor Y2). NPY2-R is a member of the Gprotein-coupled receptor super-family, and like other members has seven putative transmembrane domains. However, NPY2-R gene consists of two exons, unlike the contiguous structure of other G-protein-coupled receptor genes. NPY2-R shares a 31% sequence identity with NPY1-R. NPY2-R is expressed in the presynaptic membranes of the central nervous system, and to a lesser extent the peripheral nervous system. NPY2-R associates (from highest to lowest affinity) with carboxyl terminals of unphosphorylate Peptide YY (PYY) (phosphorylation of PYY greatly reduces its binding affinity),NPY, and Pancreatic Peptide. Depending on the cell type, NPY2-R couples with different G proteins, which act as different second messengers. NPY2-R reduces the effects of depolarization, calcium ion currents in arterial smooth muscle by through association with NPY. NPY2-R inhibits cholecystokinin octapeptide-induced, esophageal muscle contraction, through interactions with PYY and NPY.