The frizzled gene, originally identified in Drosophila melanogaster, is involved in the development of tissue polarity. The mammalian homolog of frizzled, as well as several secreted mammalian frizzled-related proteins (FRPs), have been described. The frizzled proteins contain seven transmembrane domains, a cysteine-rich domain in the extracellular region and a carboxy-terminal Ser/Thr-xxx-Val motif. They function as receptors for Wnt and are generally coupled to G proteins. The cysteine-rich domain of frizzled-8 blocks endogenous Wnts and the effects of Wnt-1 and Wnt-5 on proliferation. The mouse frizzled-8 gene, which encodes a Wnt receptor, is a potent cancer-associated activator of the Beta-catenin-TCF pathway. The frizzled-8 gene contains no introns. Frizzled-8 mRNA has been detected in fetal brain and kidney, and also in adult pancreas, skeletal muscle, kidney and heart. Frizzled is highly expressed in HeLa S3 (cervical uterus cancer) cells and A549 lung cancer cells.
Function:
Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway 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. Coreceptor along with RYK of Wnt proteins, such as WNT1
Subcellular Location:
Membrane. Golgi apparatus. Cell membrane. Colocalizes with GOPC at the Golgi apparatus.
Tissue Specificity:
Most abundant in fetal kidney, followed by brain and lung. In adult tissues, expressed in kidney, heart, pancreas and skeletal muscle.
Post-translational modifications:
Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.
Similarity:
Belongs to the G-protein coupled receptor Fz/Smo family.
Contains 1 FZ (frizzled) domain.
SWISS:
Q9H461
Gene ID:
8325
Database links:
Entrez Gene: 8325 Human
Entrez Gene: 14370 Mouse
Entrez Gene: 100909849 Rat
Entrez Gene: 364754 Rat
Omim: 606146 Human
SwissProt: Q9H461 Human
SwissProt: Q61091 Mouse
SwissProt: Q498S8 Rat
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Sample:
Lane 1: Human U87MG cell lysates
Lane 2: Human A549 cell lysates
Primary: Anti-Frizzled 8 (SL13219R) at 1/1000 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 70 kDa
Observed band size: 70 kDa
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