Conservation of a high-affinity interaction motif in Lgr5 but not Lgr4 or Lgr6.

<p>The C-terminal of tails of human Lgr4, Lgr5, Lgr6, V2R, and β2AR (Uniprot IDs: Q9BXB1, O75473, Q9HBX8, P30518, and P07550) were aligned in ClustalΩ starting with the conserved NPXXY motif at the end of transmembrane seven (Clustal X color view based upon degree of conservation, See <a href="http://jalview.org" target="_blank">jalview.org</a> for complete color table). Asterisk and arrow, respectively denote the position of the conserved palmitoylated cysteine (absent in Lgr4/5/6) and leucine. Underlined residues identify serine/threonine clusters which are necessary for Class B βarr2 affinity of the V2R. Of particular interest, is the conservation of a similar motif in Lgr5 (aa873-5) but not Lgr4, Lgr6, or β2AR. The boxed residues represent conservation of the motif necessary for Lgr5 internalization that are also seen in the V2R and β2AR.