Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family

Abstract

The cloning of a human G-protein-coupled receptor (GPCR) that specifically responds to UDP-glucose and related sugar-nucleotides has been reported recently. This receptor has important structural similarities to known members of the P2Y receptor family but also shows a distinctly different pharmacological response profile. Here, the IUPHAR Subcommittee for P2Y receptor nomenclature and classification review the current knowledge of this receptor and present their reasons for including this receptor in the P2Y receptor family as the P2Y(14) receptor.

Fig. 1.

A phylogenetic tree (dendrogram) showing the relationships among the current members of the P2Y receptor family (human P2Y₁ P2Y₂, P2Y₄, P2Y₆, P2Y₁₁, P2Y₁₂ and P2Y₁₃ receptors) and the human UDP-glucose receptor (here indicated as the P2Y₁₄ receptor). The P2Y receptors can be divided into two subgroups shown with green and blue backgrounds. Sequences were aligned using clustalx and the tree was built using the treeview software.

Fig. 2.

Alignment of putative nucleotide binding motifs in transmembrane domain 6 (TM6) and TM7 of human (h) P2Y receptors. All receptor subtypes share in TM6 the presence of the H and R/K amino acid residues proposed to be crucial for receptor activity. In P2Y₁ P2Y₂, P2Y₄, P2Y₆ and P2Y₁₁ receptors, a Y-Q/K-X-X-R motif in TM7 has also been proposed to participate in ligand binding. In P2Y₁₂ and P2Y₁₃ receptors and in the UDP-glucose receptor (here indicated as the P2Y₁₄ receptor subtype), this motif is substituted with K-E-X-X-L. Crucial amino acids for nucleotide binding are highlighted in red. Sequences were aligned using clustalx.