Cloning of a human heptahelical receptor closely related to the P2Y5 receptor

The 6H1 receptor cloned from activated chicken T cells was initially considered an orphan G-coupled receptor, but was later included in the P2Y family of receptors for purine and pyrimidine nucleotides on the basis of a significant amino acid identity and was renamed P2Y5. Analysis of the expressed sequence tag database revealed the presence of a related sequence exhibiting 63% amino acid identity with this receptor. Starting from this partial sequence, we have isolated a complete clone and identified a 1113 base pair open reading frame encoding a new G-coupled receptor that we have called P2Y5-like. This sequence exhibits 61% identity with the chicken P2Y5 sequence and 30-33% with other P2Y subtypes. A construct encoding this P2Y5-like receptor was transfected into COS-7, 1321N1, and CHO-K1 cells, and expression was documented by Northern blotting. None of the 40 nucleotides and nucleosides tested was able to elicit a response in any of four functional assays: inositol phosphate formation, stimulation or inhibition of cAMP formation, and extracellular acidification measured with a microphysiometer. These results suggest either that the natural ligand of the P2Y5-like receptor is an uncommon nucleotide or alternatively that despite its structural similarity to the P2Y family it is not a nucleotide receptor.