ABSTRACT
G protein-coupled receptors (GPCRs) are a diverse superfamily of membrane-bound receptors. The second largest subgroup of GPCRs, the Adhesion GPCRs, has 33 members in humans. Phylogenetic analysis of the entire repertoire of the seven transmembrane- domain (7TM) regions of GPCRs shows that the Adhesion GPCRs form a distinct family. Adhesion GPCRs are characterised by (1) long N termini with multiple functional domains often found in other proteins such as tyrosine kinases, integrins and cadherins, (2) highly complex genomic structure with multiple introns and splice variants and (3) a 7TM region that has no clear similarities with 7TM from other GPCRs. Several Adhesion GPCRs are known to have a role in the immune system but it is becoming more evident that many have important roles in the CNS. We speculate that the overall structural construction of the Adhesion GPCRs allows them to participate in different types of cell guidance.
Subject(s)
Receptors, G-Protein-Coupled/metabolism , Alternative Splicing , Amino Acid Sequence , Humans , Introns , Molecular Sequence Data , Phylogeny , Protein Binding , Protein Structure, Tertiary , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/classification , Receptors, G-Protein-Coupled/genetics , Sequence Alignment , Tissue DistributionABSTRACT
Using a variety of search strategies, we obtained the complete or nearly complete repertoire of trace amine receptors from humans, mice, rats, zebrafish, pufferfish, and a number of invertebrates. We found that the number of functional receptors varies from 5 to 50 in each genome, showing that this family of GPCRs has a very dynamic gene repertoire. We show that the previously cloned and characterized GPCRs from insects and mollusks are more closely related to mammalian serotonin, dopamine, and adrenalin receptors than to mammalian TA receptors. This suggests that the ability to bind TAs has arisen independently in different developmental lineages.
Subject(s)
Genetic Variation/genetics , Multigene Family , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/genetics , Amino Acid Sequence , Animals , Humans , Molecular Sequence Data , Phylogeny , Species SpecificityABSTRACT
The prolactin-releasing hormone (PRLH) is implicated in food intake and is expressed in several parts of the mammalian brain. The origin of the peptide precursor (PRH) has been unclear, and the only feature resembling other known human neuropeptide sequences is the C-terminal RF-motif, also present in the neuropeptide FF and the neuropeptide RF amide-related peptide families (RFRP). We have recently found sequences of PRH and the closely related precursor C-RF amide in chicken, shedding light on the PRH ancestry.
