The seven-pass transmembrane (7TM) cadherins are unusual class of cadherins. They have seven-pass trans­membrane domains, which have similarity to G-protein-coupled receptors (GPCRs). The 7TM cadherins are iden­tified in both vertebrates and invertebrates. The flamingo (FMI) gene is a member of that class of cadherins, which was recently identified in Drosophila. The extracellular portion of the protein consists of several cadherin repeats, EGF-like and laminin motifs. The cytoplasmic tail lacks catenin-binding sites and no putative cytoplasmic partners have been found. It is located at cell-cell boundaries in a polarized fashion and functions with Frizzled for the acquisition of proximal distal polarity of wing hair cells [11]. The members of the Frizzled family are also 7TM proteins. They resemble GPCRs in structure and can signal through G proteins or through G-protein-independent path­ways.

      Two paralogues have been found, Mouse Celsr1 [12] and human MEGF2 [13]. Both have eight EC domains, several EGF repeats and their 7TM regions also show homology to GPCRs. Human MEGF2 contain proline-rich sequences in its cytoplasmic parts through which it can interact with SH3 domains in proteins such as non receptor tyrosine kinases [3]. G-protein-coupled receptors are in­volved in cellular processes, interacting with G proteins that regulate many intracellular signaling systems, includ­ing camp, cGMP and ion channels, although the possible interaction of 7TM cadherins with G proteins is not yet proven.