FZD8

This intronless gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This gene is highly expressed in two human cancer cell lines, indicating that it may play a role in several types of cancer. The crystal structure of the extracellular cysteine-rich domain of a similar mouse protein has been determined.

Full Name

Frizzled Class Receptor 8

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.

Biological Process

Canonical Wnt signaling pathway Source: WormBase
Neuron differentiation Source: UniProtKB

Cellular Location

Golgi apparatus; Cell membrane; Membrane. Colocalizes with GOPC at the Golgi apparatus.

Topology

Extracellular: 28-275
Helical: 276-296
Cytoplasmic: 297-312
Helical: 313-333
Extracellular: 334-396
Helical: 397-417
Cytoplasmic: 418-439
Helical: 440-460
Extracellular: 461-483
Helical: 484-504
Cytoplasmic: 505-532
Helical: 533-553
Extracellular: 554-584
Helical: 585-605
Cytoplasmic: 606-694

PTM

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.