Motifs in Frizzled proteins. SS, signal sequence; CRD, cysteine-rich domain. The CRD is extracellular and binds ligands, including Wnts and Norrin. The carboxyl terminus is intracellular and contains a proximal KTXXXW motif (in the single-letter amino-acid code, where X is any amino acid), which is highly conserved in Frizzleds and is required for canonical signaling.