FRI

Frizzled
FRI
SMART accession number:SM00063
Description: Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell along the anteroposterior axis. Homologues of the N-terminal region of frizzled exist either as transmembrane or secreted molecules. Frizzled homologues are reported to be receptors for the Wnt growth factors. (Not yet in MEDLINE: the FRI domain occurs in several receptor tyrosine kinases [Xu, Y.K. and Nusse, Curr. Biol. 8 R405-R406 (1998); Masiakowski, P. and Yanopoulos, G.D., Curr. Biol. 8, R407 (1998)].
Interpro abstract (IPR020067):

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 frizbee (Frzb) family; secreted frizzled-like proteins.
  • Smoothened; another 7TM receptor involved in hedgehog signaling.
  • Carboxpeptidase Z (CPZ).
  • Transmembrane serine protease corin.
  • 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 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 [(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)].

GO function:protein binding (GO:0005515)
Family alignment:
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There are 2284 FRI domains in 2113 proteins in SMART's nrdb database.

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