<p>The frizzled (fz) domain is an extracellular domain of about 120 amino acids.It was first identified in the alpha-1 chain of type XVIII collagen and in members of the Frizzled family of seven transmembrane (7TM) proteins which act as receptors for secreted Wingless (Wg)/Wnt glycoproteins [<cite idref="PUB00033721"/>]. In addition to these proteins, one or two copies of the fz domain are also found [<cite idref="PUB00001039"/>, <cite idref="PUB00033661"/>, <cite idref="PUB00033662"/>, <cite idref="PUB00005486"/>, <cite idref="PUB00033722"/>] in:<ul><li>The frizbee (Frzb) family; secreted frizzled-like proteins.</li><li>Smoothened; another 7TM receptor involved in hedgehog signaling.</li><li>Carboxpeptidase Z (CPZ).</li><li>Transmembrane serine protease corin.</li><li>Two receptor tyrosine kinases (RTKs) subfamilies, the Ror family and the muscle-specific kinase (MuSK) family.</li></ul></p><p>As the fz domain contains 10 cysteines which are largely conserved, it has also been called cysteine-rich domain (CRD) [<cite idref="PUB00033721"/>]. The fz domain also contains several other highly conserved residues, for example, a basic amino acid follows C6, and a conserved proline residues lies four residues C-terminal to C9 [<cite idref="PUB00005486"/>]. The crystal structure of a fz domain shows that it is predominantly alpha-helical with all cysteines forming disulphide bonds. In addition to helical regions, two short beta-strands at the N terminus form a minimal beta-sheet with the second beta sheet passing through a knot created by disulphide bonds [<cite idref="PUB00033723"/>].</p><p>Several fz domains have been shown to be both necessary and sufficient for Wg/Wnt ligand binding, strongly suggesting that the fz domain is a Wg/Wnt interacting domain [<cite idref="PUB00004238"/>, <cite idref="PUB00033724"/>].</p> Frizzled domain