Figure 6. Overview of mutations in LRP5 and TSPAN12. A: Protein sequence alignment of human LRP5 with its orthologs in family A. B: The location of the mutation on the TSPAN12 protein domains (structural features of tetraspanins were obtained from Hemler et al. (2005)). Tetraspanins contain four transmembrane domains, a small extracellular loop (EC1), a large extracellular loop (EC2), and a tiny inner loop. Most protein–protein interaction sites and monoclonal antibody epitopes map to EC2. All tetraspanins contain a CCG motif and two other conserved cysteines (green), which are arranged to form two intramolecular disulfide bonds (red lines). Many tetraspanins contain two additional cysteines (yellow), which form another intramolecular disulfide bond (dotted red line).