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 [ PUBMED:7876242 ]. In addition … expand

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 [ PUBMED:7876242 ]. In addition to these proteins, one or two copies of the fz domain are also found [ PUBMED:9637908 PUBMED:9637909 PUBMED:10082384 PUBMED:9852758 PUBMED:10329693 ] in:

• The Frzb family; secreted frizzled-like proteins.
• Smoothened; another 7TM receptor involved in hedgehog signaling.
• Carboxpeptidase Z (CPZ).
• Transmembrane serine protease corin (atrial natriuretic peptide-converting enzyme).
• Two receptor tyrosine kinases (RTKs) subfamilies, the Ror family and the muscle-specific kinase (MuSK) family.

As the fz domain contains 10 cysteines which are largely conserved, it has also been called cysteine-rich domain (CRD) [ PUBMED:7876242 ]. 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 [ PUBMED:9852758 ]. The crystal structure of a fz domain shows that it is predominantly α-helical with all cysteines forming disulphide bonds. In addition to helical regions, two short β-strands at the N terminus form a minimal β-sheet with the second β sheet passing through a knot created by disulphide bonds [ PUBMED:11452312 ].

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 [ PUBMED:8717036 PUBMED:9326585 ].