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首页> 外文期刊>BMC Genomics >GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors
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GPR99, a new G protein-coupled receptor with homology to a new subgroup of nucleotide receptors

机译：GPR99，一种新的G蛋白偶联受体，与新的核苷酸受体亚组同源

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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.
机译：背景技术基于序列相似性，G蛋白偶联受体（GPR）的超家族可以细分为几个亚家族，其成员通常共享相似的配体。人类基因组计划提供的序列数据使我们能够通过计算机同源筛选来鉴定新的GPR，并预测其配体。结果通过搜索具有已知核苷酸受体的人类基因组数据库，我们发现了GPR99（一种新的孤儿GPR）的基因。 GPR99的mRNA在肾脏和胎盘中发现。系统发育分析将GPR99分组为GPR的P2Y子家族。基于系统发育树，我们提出了将P2Y核苷酸受体的新分类，分为两个亚组，预测GPR99的核苷酸配体。通过测定异源表达的GPR99上已知的核苷酸配体，我们无法鉴定出特异性活化物质，表明它们不是GPR99的激动剂或GPR99在细胞表面未表达。对P2Y亚家族所有基因的染色体定位分析表明，“ a”亚组的所有成员在3q24染色体上的编码少于370 kb，而“ b”亚组的基因一方面聚集成11号染色体13q13。 5和另一个在染色体3q24-25.1上接近亚组“ a”的位置。因此，P2Y亚家族是局部基因扩增的显着实例。结论我们确定了一种新的孤儿受体GPR99，与G蛋白偶联核苷酸受体家族同源。系统发生分析将该家族分为不同的亚组，预测GPR99的核苷酸配体。

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