For Research Use Only. Not for use in diagnostic procedures.

Chromosome: 11; NC_000011.9 (86656717..86666440, complement). Location: 11q14.2

Purified
95% (SDS-PAGE)

Supplied as a lyophilized powder from PBS. Carrier free. Reconstitute with 400ug/ml PBS.

Lyophilized powder may be stored at -20 degree C. Reconstitute with 400ug/ml PBS. Aliquot and store at -20 degree C. Reconstituted product is stable for 6 months at -20 degree C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

Small volumes of FZD4 recombinant protein vial(s) may occasionally become entrapped in the seal of the product vial during shipment and storage. If necessary, briefly centrifuge the vial on a tabletop centrifuge to dislodge any liquid in the container`s cap. Certain products may require to ship with dry ice and additional dry ice fee may apply.

Frizzled-4, designated CD344, is a 7-transmembrane glycoprotein of the Frizzled family within the G-protein coupled receptor superfamily. Frizzled proteins function as receptors for Wnt proteins and can activate canonical Wnt/beta-catenin signaling as well as planar cell polarity and calcium flux pathways. Frizzled-4 is particularly important in angiogenic Wnt pathway signaling. Frizzleds contain a divergent N-terminal signal peptide, a highly conserved ~120aa cysteine-rich domain (CRD), a variable length linker region, seven transmembrane domains, and a variable-length C-terminal tail. The human Frizzled-4 cDNA encodes 537aa with a 36aa signal sequence and a 186aa N-terminal extracellular sequence. The portion expressed in this product includes aa37-180, and shares 93%, 93%, 94%, 95% and 97% identity with the corresponding region of mouse, rat, bovine, canine and equine Frizzled-4, respectively. This portion competes for Wnt binding with endogenous receptors. A human 122aa soluble form that diverges at aa95 is proposed to be a positive regulator of Wnt signaling pathways. Frizzled-4 is unusual in binding a non-wnt ligand, Norrin, in addition to binding Wnt ligands. Norrin binds the Frizzled-4 CRD, activates Wnt signaling pathways and uses LRP5/ 6 as co-receptors. Deletion of either Frizzled-4 or Norrin in mice results in a similar phenotype including malformation of vasculature in the retina, cerebellar degeneration, and loss of hair cells in the inner ear. In humans, blindness due to familial exudative vitreoretinopathy (FEVR) is associated with mutations producing loss of function of Frizzled-4 or Norrin, designated EVR1 and EVR2, respectively. Frizzled-4 expression has been found in many tissues, including mouse ovary, where it influences corpus luteum vasculogenesis and is necessary for fertility.

Molecular Biology; MB-Wnt Proteins

58-60kD[Similar Products]

frizzled family receptor 4

frizzled-4; frizzled homolog 4; WNT receptor frizzled-4; frizzled 4, seven transmembrane spanning receptor

Frizzled-4

Fz-4; hFz4??[Similar Products]

FZD4_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: Receptor, GPCR; Membrane protein, multi-pass; GPCR, Fz/Smo family; Membrane protein, integral

Chromosomal Location of Human Ortholog: 11q14.2

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

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

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

Disease: Exudative Vitreoretinopathy 1

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