FMRFamide (Phe-Met-Arg-Phe) receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors
This group includes Drosophila melanogaster G-protein coupled FMRFamide (Phe-Met-Arg-Phe-NH2) receptor DrmFMRFa-R and related invertebrate receptors, as well as the vertebrate proteins GPR139 and GPR142. DrmFMRFa-R binds with high affinity to FMRFamide and intrinsic FMRFamide-related peptides. FMRFamide is a neuropeptide from the family of FMRFamide-related peptides (FaRPs), which all containing a C-terminal RFamide (Arg-Phe-NH2) motif and have diverse functions in the central and peripheral nervous systems. FMRFamide is an important neuropeptide in many types of invertebrates such as insects, nematodes, molluscs, and worms. In invertebrates, the FMRFamide-related peptides are involved in the regulation of heart rate, blood pressure, gut motility, feeding behavior, and reproduction. On the other hand, in vertebrates such as mice, they play a role in the modulation of morphine-induced antinociception. Orphan receptors GPR139 and GPR142 are very closely related G protein-coupled receptors, but they have different expression patterns in the brain and in other tissues. These receptors couple to inhibitory G proteins and activate phospholipase C. Studies suggested that dimer formation may be required for their proper function. GPR142 is predominantly expressed in pancreatic beta-cells and mediates enhancement of glucose-stimulated insulin secretion, whereas GPR139 is mostly expressed in the brain and is suggested to play a role in the control of locomotor activity. Tryptophan and phenylalanine have been identified as putative endogenous ligands of GPR139.
Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
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