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Frizzled Family

Frizzled is a family of G protein-coupled receptor proteins that function in multiple signal transduction pathways. It could serve as receptor in one of the three signaling pathways including the canonical Wnt/β-catenin pathway, Wnt/calcium pathway, and planar cell polarity (PCP) pathway. Frizzled proteins have been identified in different animals, from sponges to humans. They play critical roles in the regulation of cell polarity and are essential in governing cell polarity, cell proliferation, formation of neural synapses, embryonic development, and many other processes in developing and adult organisms. Mutations in the human FZD1 receptor are related to familial exudative vitreoretinopathy which is a rare disease affecting the retina of the eye, and the vitreous, the clear fluid inside the eye.

SS, signal sequence; CRD, cysteine-rich domain. The CRD is extracellular and binds ligands, including Wnts and Norrin. The carboxyl terminus is intracellular and contains a proximal KTXXXW motif (in the single-letter amino-acid code, where X is any amino acid), which is highly conserved in Frizzleds and is required for canonical signaling. Fig.1 Motifs in Frizzled proteins. (Huang. 2004)

Here shows part of frizzled receptors in humans. Frizzled genes and the proteins they encode have been identified in a range of animals, from sponges to humans. Sequence analysis results suggest that the ten-human frizzled genes can be divided into four main clusters. Frizzled genes from different clusters share 20% to 40% sequence similarity. FZD1, FZD2, and FZD7 share about 75% identity. FZD5 and FZD8 share 70% identity. FZD4, FZD9, and FZD10 share 65% identity. FZD3 and FZD6 share 50% amino acid identity.

Human Frizzled Receptor Members
FZD1 FZD2 FZD3 FZD4 FZD5
FZD6 FZD7 FZD8 FZD9 FZD10

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Reference

  1. Huang HC, et al. (2014). The Frizzled family: receptors for multiple signal transduction pathways. Genome Biol. 5(7): 234.

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