The Repertoire of G-Protein–Coupled Receptors in Fully Sequenced Genomes

Abstract

The superfamily of G-protein-coupled receptors (GPCRs) is one of the largest and most studied families of proteins. We created Hidden Markov Models derived from sorted groups of GPCRs from our previous detailed phylogenetic classification of human GPCRs and added several other models derived from receptors not found in mammals. We used these models to search entire Genscan data sets from 13 species whose genomes are nearly completely sequenced. We found more than 5000 unique GPCRs that were divided into 15 main groups, and the largest one, the Rhodopsin family, was subdivided into 13 subclasses. The results show that the main families in the human genome, Glutamate, Rhodopsin, Adhesion, Frizzled, and Secretin, arose before the split of nematodes from the chordate lineage. Moreover, several of the subgroups of the Rhodopsin family arose before the split of the linage leading to vertebrates. We also searched expressed sequence tag (EST) databases and identified more than 20,000 sequences that match GPCRs. Although the GPCRs represent typically 1 to 2% of the Genscan predictions, the ESTs that match GPCRs are typically only 0.01 to 0.001%, indicating that GPCRs in most of the groups are expressed at low levels. We also provide searchable data sets that may be used for annotation and further detailed analysis of the GPCR family. This study provides an extensive overview of the expansion of the gene repertoire for families and subgroups of GPCRs.A tremendous amount of primary sequence information has been made available from the recent sequencing projects, providing a near-to-full coverage of the entire genome from a diversity of animal species. The fully sequenced genomes include the mammals mouse and human, two species from the bony fish line (pufferfish Takifugu rubripes and zebrafish Danio rerio), two protochordates from the tunicate linage (Ciona intestinalis and Ciona savignyi) together with two nematodes (Caenorhabditis elegans and Caenorhabditis briggsae), and the insects fruit fly (Drosophila melanogaster) and mosquito (Anopheles gambiae). Moreover, the plants thale cress (Arabidopsis thaliana) and rice (Oryza sativa) are sequenced, as well as several unicellular species of yeast from the fungi linage such as the bakers' yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces cerevisiae).

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

“…Many GPCRs exist. In fact, the GPCR superfamily is the largest class of cell surface receptors and almost 1,000 GPCRs are thought to be encoded by the human genome (Fredriksson & Schioth, 2005;Perez, 2003, Takeda et al, 2002Vassilatis et al, 2003). These receptors have diverse roles in that they regulate overall organism homeostasis as well as embryo development, and they are also involved in learning, memory, vision, smell and taste.…”

L’hétérodimérisation des récepteurs couplés aux protéines G

“…À cet égard, ce concept, qui est illustré par l'abondance d'exemples d'hétérodimérisation de plusieurs récepteurs nucléaires orphelins [10][11][12], peut être élargi à l'ensemble des RCPG orphelins et stimuler ainsi de nouvelles stratégies de recherche pour la fonction de ces récepteurs. 1 La vitréorétinopathie exsudative familiale est une dystrophie rétinovitréenne rare caractérisée par un arrêt prématuré de la vascularisation de la rétine périphérique (source : Orphanet).…”

Visual Rhodopsin Sees the Light: Structure and Mechanism of G Protein Signaling

“…These heptahelical integral membrane proteins are of immense importance in human physiology and health as evidenced by the fact that virtually every cell type expresses a subset of GPCRs. With the sequencing of the human genome complete, it is now abundantly clear that upwards of 950 genes encode GPCRs (1). The mammalian GPCRs are typically grouped by similar amino acid sequences into the three distinct families: A, B, and C. For most GPCRs, the external stimulus (agonist) leading to receptor activation is a small molecule that binds to a region of the transmembrane (TM) domain and triggers conformational changes that are transmitted to the cytoplasmic surface of the receptor to facilitate the activation of intracellular heterotrimeric guanine nucleotide-binding proteins (G proteins).…”