Limits...
GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors.

Wittenberger T, Hellebrand S, Munck A, Kreienkamp HJ, Schaller HC, Hampe W - BMC Genomics (2002)

Bottom Line: The mRNA of GPR99 was found in kidney and placenta.We identified a new orphan receptor, GPR99, with homology to the family of G protein-coupled nucleotide receptors.Phylogenetic analysis separates this family into different subgroups predicting a nucleotide ligand for GPR99.

View Article: PubMed Central - HTML - PubMed

Affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistr, 52, D-20246 Hamburg, Germany. timo.wittenberger@altanapharma.com

ABSTRACT

Background: Based on sequence similarity, the superfamily of G protein-coupled receptors (GPRs) can be subdivided into several subfamilies, the members of which often share similar ligands. The sequence data provided by the human genome project allows us to identify new GPRs by in silico homology screening, and to predict their ligands.

Results: By searching the human genomic database with known nucleotide receptors we discovered the gene for GPR99, a new orphan GPR. The mRNA of GPR99 was found in kidney and placenta. Phylogenetic analysis groups GPR99 into the P2Y subfamily of GPRs. Based on the phylogenetic tree we propose a new classification of P2Y nucleotide receptors into two subgroups predicting a nucleotide ligand for GPR99. By assaying known nucleotide ligands on heterologously expressed GPR99, we could not identify specifically activating substances, indicating that either they are not agonists of GPR99 or that GPR99 was not expressed at the cell surface. Analysis of the chromosomal localization of all genes of the P2Y subfamily revealed that all members of subgroup "a" are encoded by less than 370 kb on chromosome 3q24, and that the genes of subgroup "b" are clustered on one hand to chromosome 11q13.5 and on the other on chromosome 3q24-25.1 close to the subgroup "a" position. Therefore, the P2Y subfamily is a striking example for local gene amplification.

Conclusions: We identified a new orphan receptor, GPR99, with homology to the family of G protein-coupled nucleotide receptors. Phylogenetic analysis separates this family into different subgroups predicting a nucleotide ligand for GPR99.

No MeSH data available.


Alignment of human GPR99 with its closest relatives hGPR91 and hP2Y1. Amino acid residues identical to GPR99 are highlighted. The seven transmembrane regions (TM) are overlined, the N-glycosylation signals of GPR99 (•), and the position of the subgroup-specific motif at the beginning of transmembrane domain seven (*) are indicated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC117779&req=5

Figure 2: Alignment of human GPR99 with its closest relatives hGPR91 and hP2Y1. Amino acid residues identical to GPR99 are highlighted. The seven transmembrane regions (TM) are overlined, the N-glycosylation signals of GPR99 (•), and the position of the subgroup-specific motif at the beginning of transmembrane domain seven (*) are indicated.

Mentions: GPR99 shares 36% identical amino acids both with the P2Y1 receptor (57% similarity) and with GPR91 (55% similarity) as its closest homologs (Fig. 2). "Fingerprint" analysis for GPR subtypes [4] also groups GPR99 into the P2 purinoceptor subfamily. No receptors from other species with a similar degree of relatedness were identified in the databases.


GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors.

Wittenberger T, Hellebrand S, Munck A, Kreienkamp HJ, Schaller HC, Hampe W - BMC Genomics (2002)

Alignment of human GPR99 with its closest relatives hGPR91 and hP2Y1. Amino acid residues identical to GPR99 are highlighted. The seven transmembrane regions (TM) are overlined, the N-glycosylation signals of GPR99 (•), and the position of the subgroup-specific motif at the beginning of transmembrane domain seven (*) are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC117779&req=5

Figure 2: Alignment of human GPR99 with its closest relatives hGPR91 and hP2Y1. Amino acid residues identical to GPR99 are highlighted. The seven transmembrane regions (TM) are overlined, the N-glycosylation signals of GPR99 (•), and the position of the subgroup-specific motif at the beginning of transmembrane domain seven (*) are indicated.
Mentions: GPR99 shares 36% identical amino acids both with the P2Y1 receptor (57% similarity) and with GPR91 (55% similarity) as its closest homologs (Fig. 2). "Fingerprint" analysis for GPR subtypes [4] also groups GPR99 into the P2 purinoceptor subfamily. No receptors from other species with a similar degree of relatedness were identified in the databases.

Bottom Line: The mRNA of GPR99 was found in kidney and placenta.We identified a new orphan receptor, GPR99, with homology to the family of G protein-coupled nucleotide receptors.Phylogenetic analysis separates this family into different subgroups predicting a nucleotide ligand for GPR99.

View Article: PubMed Central - HTML - PubMed

Affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistr, 52, D-20246 Hamburg, Germany. timo.wittenberger@altanapharma.com

ABSTRACT

Background: Based on sequence similarity, the superfamily of G protein-coupled receptors (GPRs) can be subdivided into several subfamilies, the members of which often share similar ligands. The sequence data provided by the human genome project allows us to identify new GPRs by in silico homology screening, and to predict their ligands.

Results: By searching the human genomic database with known nucleotide receptors we discovered the gene for GPR99, a new orphan GPR. The mRNA of GPR99 was found in kidney and placenta. Phylogenetic analysis groups GPR99 into the P2Y subfamily of GPRs. Based on the phylogenetic tree we propose a new classification of P2Y nucleotide receptors into two subgroups predicting a nucleotide ligand for GPR99. By assaying known nucleotide ligands on heterologously expressed GPR99, we could not identify specifically activating substances, indicating that either they are not agonists of GPR99 or that GPR99 was not expressed at the cell surface. Analysis of the chromosomal localization of all genes of the P2Y subfamily revealed that all members of subgroup "a" are encoded by less than 370 kb on chromosome 3q24, and that the genes of subgroup "b" are clustered on one hand to chromosome 11q13.5 and on the other on chromosome 3q24-25.1 close to the subgroup "a" position. Therefore, the P2Y subfamily is a striking example for local gene amplification.

Conclusions: We identified a new orphan receptor, GPR99, with homology to the family of G protein-coupled nucleotide receptors. Phylogenetic analysis separates this family into different subgroups predicting a nucleotide ligand for GPR99.

No MeSH data available.