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.||Source:|Murine myeloma cell line, NS0-derived, Phe37-Glu180.||Molecular Weight: 58-60kD (SDA-PAGE, reducing conditions) ||Biological Activity:|Measured by its binding ability in a functional ELISA. In a 100ul reaction mixture containing Wnt-5a at 100ng/ml and Frizzled-4/Fc Chimera dilutions at 0.1-2,000ng/ml, the concentration of Frizzled-4/Fc Chimera that produces 50% of the optimal binding response is found to be ~15-60ng/ml.||Endotoxin: ≤1EU/ug (LAL) ||Storage and Stability:|Lyophilized powder may be stored at -20°C. Reconstitute with 400ug/ml PBS. Aliquot and store at -20°C. Reconstituted product is stable for 6 months at -20°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.

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