Frizzled-4 (FZD4) ELISA Kit for Human

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. [provided by RefSeq, Jul 2008]

FZD4: Receptor for Wnt proteins. Most of 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. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. 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. Defects in FZD4 are the cause of vitreoretinopathy exudative type 1 (EVR1); also known as autosomal dominant familial exudative vitreoretinopathy (FEVR) or Criswick- Schepens syndrome. EVR1 is 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. Belongs to the G-protein coupled receptor Fz/Smo family.

Protein type: GPCR, Fz/Smo family; Receptor, GPCR; Membrane protein, multi-pass; Membrane protein, integral

Chromosomal Location of Human Ortholog: 11q14.2

Cellular Component: cell surface; integral to membrane; integral to plasma membrane; intercellular junction; plasma membrane

Molecular Function: cytokine binding; G-protein coupled receptor activity; PDZ domain binding; protein binding; protein heterodimerization activity; protein homodimerization activity; ubiquitin protein ligase binding; Wnt receptor activity; Wnt-protein binding

Biological Process: G-protein coupled receptor protein signaling pathway; locomotion during locomotory behavior; neuron differentiation; positive regulation of JNK activity; positive regulation of transcription factor activity; positive regulation of transcription, DNA-dependent; progesterone secretion; regulation of vascular endothelial growth factor receptor signaling pathway; sensory perception of sound; vasculogenesis; Wnt receptor signaling pathway; Wnt receptor signaling pathway through beta-catenin; Wnt receptor signaling pathway, calcium modulating pathway

Disease: Exudative Vitreoretinopathy 1