The frizzled (fz) domain is an extracellular domain of about 120 amino acids.
It was first identified in the α-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 (see <PDOC00219>)
. In addition to these proteins, one or two copies of the fz domain are
also found [2,3,4,5,6] 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) . 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 . The crystal structure of a fz domain shows that it is predominantly
α-helical with all cysteines forming disulfide 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 disulfide
The schematic representation of the structure of a typical fz domain is shown
'C': conserved cysteine involved in a disulfide bond.
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 [8,9,10].
The profile we developed covers the entire fz domain.
October 2002 / Text revised.
PROSITE method (with tools and information) covered by this documentation:
Rehn M., Pihlajaniemi T.
Identification of three N-terminal ends of type XVIII collagen chains and tissue-specific differences in the expression of the corresponding transcripts. The longest form contains a novel motif homologous to rat and Drosophila frizzled proteins.
Rattner A., Hsieh J.-C., Smallwood P.M., Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J.
Proc. Natl. Acad. Sci. U.S.A. 94:2859-2863(1997).
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