UniProt functional annotation for O75084



	UniProt functional annotation for O75084

UniProt code: O75084.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000250|UniProtKB:Q61090, ECO:0000269|PubMed:26126266}.

Function: (Microbial infection) Acts as a receptor for C.difficile toxin TcdB in the colonic epithelium. {ECO:0000269|PubMed:27680706}.

Subunit: Interacts with MAGI3 (By similarity). Interacts with DVL1 (By similarity). Interacts with CCDC88C/DAPLE; the interaction displaces DVL1 from FZD7, leading to inhibition of canonical Wnt signaling and triggering of non-canonical Wnt responses (PubMed:26126266). Interacts with MYOC (PubMed:19188438). Binds to SDCBP; this interaction is increased by inositol trisphosphate (IP3) (PubMed:27386966). Interacts with glypican GPC3 (PubMed:24496449). {ECO:0000250|UniProtKB:Q61090, ECO:0000269|PubMed:19188438, ECO:0000269|PubMed:24496449, ECO:0000269|PubMed:26126266}.

Subunit: (Microbial infection) Interacts with C.difficile toxin TcdB; frizzled receptors constitute the major host receptors for TcdB in the colonic epithelium. {ECO:0000269|PubMed:27680706}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:27386966}; Multi-pass membrane protein {ECO:0000269|PubMed:27386966}. Endosome membrane {ECO:0000269|PubMed:27386966}; Multi-pass membrane protein {ECO:0000269|PubMed:27386966}. Note=Associated to the plasma membrane in the presence of FZD7 and phosphatidylinositol 4,5-bisphosphate (PIP2). Localized in recycling endosomes in other conditions. {ECO:0000269|PubMed:27386966}.

Tissue specificity: High expression in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta. Specifically expressed in squamous cell esophageal carcinomas.

Domain: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway. {ECO:0000250}.

Domain: The FZ domain is involved in binding with Wnt ligands. {ECO:0000250}.

Ptm: Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. {ECO:0000250}.

Similarity: Belongs to the G-protein coupled receptor Fz/Smo family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000250\|UniProtKB:Q61090, ECO:0000269\|PubMed:26126266}.



Function:		(Microbial infection) Acts as a receptor for C.difficile toxin TcdB in the colonic epithelium. {ECO:0000269\|PubMed:27680706}.


Subunit:		Interacts with MAGI3 (By similarity). Interacts with DVL1 (By similarity). Interacts with CCDC88C/DAPLE; the interaction displaces DVL1 from FZD7, leading to inhibition of canonical Wnt signaling and triggering of non-canonical Wnt responses (PubMed:26126266). Interacts with MYOC (PubMed:19188438). Binds to SDCBP; this interaction is increased by inositol trisphosphate (IP3) (PubMed:27386966). Interacts with glypican GPC3 (PubMed:24496449). {ECO:0000250\|UniProtKB:Q61090, ECO:0000269\|PubMed:19188438, ECO:0000269\|PubMed:24496449, ECO:0000269\|PubMed:26126266}.
Subunit:		(Microbial infection) Interacts with C.difficile toxin TcdB; frizzled receptors constitute the major host receptors for TcdB in the colonic epithelium. {ECO:0000269\|PubMed:27680706}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:27386966}; Multi-pass membrane protein {ECO:0000269\|PubMed:27386966}. Endosome membrane {ECO:0000269\|PubMed:27386966}; Multi-pass membrane protein {ECO:0000269\|PubMed:27386966}. Note=Associated to the plasma membrane in the presence of FZD7 and phosphatidylinositol 4,5-bisphosphate (PIP2). Localized in recycling endosomes in other conditions. {ECO:0000269\|PubMed:27386966}.
Tissue specificity:		High expression in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta. Specifically expressed in squamous cell esophageal carcinomas.
Domain:		Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway. {ECO:0000250}.
Domain:		The FZ domain is involved in binding with Wnt ligands. {ECO:0000250}.
Ptm:		Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. {ECO:0000250}.
Similarity:		Belongs to the G-protein coupled receptor Fz/Smo family. {ECO:0000305}.