Function: Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.
Subcellular location: Membrane; Multi-pass membrane protein
By similarity. Cell membrane; Multi-pass membrane protein
By similarity.
Tissue specificity: Expressed broadly in cranial ectoderm. Also expressed in the developing somites and in other cranial placodes, including the olfactory, lens, otic placodes (lateral half of the vesicle) and epibranchial placodes. Low level of expression in all the mesoderm derivatives in the limb buds.
Developmental stage: First detected as stage 6 in the forming neural tube and somites, but not in trunk surface ectoderm. By stage 8, expression persists in the cranial ectoderm and is up-regulated in the presomptive olfactory placodes. By stages 11-12, expression declines in the neural tube, but not in the cranial ectoderm; in somites, expressed all along the rostral-caudal axis as well as in presegmental mesenchyme caudal to the developing somites. Lens and otic placode expression first visible at stage 12, strongest at stages 13-16. Detected uniformly in ectoderm and mesenchyme of the limb primordia at stage 17. By stage 18, decrease of ectodermal, otic, lens and olfactory placode expression; expression appears in the epibranchial placodes. By stages 22-30, highest levels in the most distal mesoderm of the autopod, in the ventricular zone of the neural tube from the forebrain to the spinal cord, in the dermomyotomes and the tail buds.
Domain: Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway
By similarity.The FZ domain is involved in binding with Wnt ligands
By similarity.
Sequence similarities: Belongs to the G-protein coupled receptor Fz/Smo family.Contains 1 FZ (frizzled) domain.
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