FZD4

This 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 protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence.

frizzled class receptor 4

Receptor for Wnt proteins (PubMed:30135577).

Most frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes (PubMed:30135577).

Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP) (By similarity).

In retina, it can be activated by Wnt protein-binding and also by Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs (By similarity).

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.

Canonical Wnt signaling pathway Source: UniProtKB
Cellular response to leukemia inhibitory factor Source: Ensembl
Cellular response to retinoic acid Source: UniProtKB
Cerebellum vasculature morphogenesis Source: Ensembl
Extracellular matrix-cell signaling Source: Ensembl
Locomotion involved in locomotory behavior Source: Ensembl
Negative regulation of canonical Wnt signaling pathway Source: GO_Central
Negative regulation of cell-substrate adhesion Source: BHF-UCL
Neuron differentiation Source: UniProtKB
Non-canonical Wnt signaling pathway Source: ARUK-UCL
Norrin signaling pathway Source: BHF-UCL
Positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
Positive regulation of JUN kinase activity Source: Ensembl
Positive regulation of neuron projection arborization Source: ARUK-UCL
Positive regulation of transcription, DNA-templated Source: BHF-UCL
Progesterone secretion Source: Ensembl
Regulation of vascular endothelial growth factor receptor signaling pathway Source: Ensembl
Retinal blood vessel morphogenesis Source: Ensembl
Retina vasculature morphogenesis in camera-type eye Source: BHF-UCL
Sensory perception of sound Source: Ensembl
Substrate adhesion-dependent cell spreading Source: Ensembl
Vasculogenesis Source: Ensembl
Wnt signaling pathway Source: ARUK-UCL
Wnt signaling pathway, calcium modulating pathway Source: BHF-UCL

Cell membrane

Vitreoretinopathy, exudative 1 (EVR1):
A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history.

Extracellular: 37-212
Helical: 213-243
Cytoplasmic: 244-249
Helical: 250-275
Extracellular: 276-299
Helical: 300-333
Cytoplasmic: 334-336
Helical: 337-365
Extracellular: 366-383
Helical: 384-418
Cytoplasmic: 419-431
Helical: 432-460
Extracellular: 461-473
Helical: 474-495
Cytoplasmic: 496-537

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