FZD7

Members of the 'frizzled' gene family encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The FZD7 protein contains an N-terminal signal sequence, 10 cysteine residues typical of the cysteine-rich extracellular domain of Fz family members, 7 putative transmembrane domains, and an intracellular C-terminal tail with a PDZ domain-binding motif. FZD7 gene expression may downregulate APC function and enhance beta-catenin-mediated signals in poorly differentiated human esophageal carcinomas.

Full Name

Frizzled Class Receptor 7

Function

Receptor for Wnt proteins. Most 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. Activation by WNT8 induces expression of beta-catenin target genes (By similarity).

Following ligand activation, binds to CCDC88C/DAPLE which displaces DVL1 from FZD7 and leads to inhibition of canonical Wnt signaling, activation of G-proteins by CCDC88C and triggering of non-canonical Wnt responses (PubMed:26126266).

May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.

(Microbial infection) Acts as a receptor for C.difficile toxin TcdB in the colonic epithelium.

Biological Process

Canonical Wnt signaling pathway Source: UniProtKB
Cellular response to retinoic acid Source: UniProtKB
Mesenchymal to epithelial transition Source: BHF-UCL
Negative regulation of cardiac muscle cell differentiation Source: BHF-UCL
Negative regulation of cell-substrate adhesion Source: BHF-UCL
Negative regulation of ectodermal cell fate specification Source: BHF-UCL
Neuron differentiation Source: UniProtKB
Non-canonical Wnt signaling pathway via JNK cascade Source: BHF-UCL
Positive regulation of epithelial cell proliferation involved in wound healing Source: BHF-UCL
Positive regulation of JNK cascade Source: BHF-UCL
Positive regulation of phosphorylation Source: BHF-UCL
Positive regulation of transcription, DNA-templated Source: BHF-UCL
Regulation of canonical Wnt signaling pathway Source: BHF-UCL
Regulation of transcription, DNA-templated Source: BHF-UCL
Skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration Source: Ensembl
Somatic stem cell division Source: Ensembl
Stem cell population maintenance Source: BHF-UCL
Substrate adhesion-dependent cell spreading Source: Ensembl
T cell differentiation in thymus Source: Ensembl
Wnt signaling pathway, planar cell polarity pathway Source: ParkinsonsUK-UCL

Cellular Location

Cell membrane; Endosome membrane. Associated to the plasma membrane in the presence of FZD7 and phosphatidylinositol 4,5-bisphosphate (PIP2). Localized in recycling endosomes in other conditions.

Topology

Extracellular: 33-256
Helical: 257-277
Cytoplasmic: 278-288
Helical: 289-309
Extracellular: 310-336
Helical: 337-357
Cytoplasmic: 358-379
Helical: 380-400
Extracellular: 401-423
Helical: 424-444
Cytoplasmic: 445-470
Helical: 471-491
Extracellular: 492-528
Helical: 529-549
Cytoplasmic: 550-574

PTM

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