Frizzled domain (IPR020067)

Short name: Frizzled_dom

Overlapping homologous superfamilies

Domain relationships


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 [PMID: 7876242]. In addition to these proteins, one or two copies of the fz domain are also found [PMID: 9637908, PMID: 9637909, PMID: 10082384, PMID: 9852758, PMID: 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) [PMID: 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 [PMID: 9852758]. 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 [PMID: 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 [PMID: 8717036, PMID: 9326585].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0005515 protein binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles