FZD9 Membrane Protein Introduction

Introduction of FZD9

Frizzled-9 is a class of proteins encoded by the FZD9 gene, also known as CD349. FZD9 acts as a 7-transmembrane domain protein for Wnt signaling receptors. The FZD9 gene is located in the common deletion region of Williams syndrome on chromosome 7, and the gene's heterozygous deletion contributes to the Williams syndrome phenotype. The FZD9 expression is found in brain, testis, eyes, skeletal muscle and kidney.

Basic Information of FZD9
Protein Name	Frizzled-9 (Fz-9) (hFz9) (FzE6) (CD antigen CD349)
Gene Name	FZD9
Aliases	FZD9, CD349, FZD3, frizzled class receptor 9
Organism	Homo sapiens (Human)
UniProt ID	O00144
Transmembrane Times	7
Length (aa)	591
Sequence	MAVAPLRGALLLWQLLAAGGAALEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTS QGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARLRCAPIMEQFN FGWPDSLDCARLPTRNDPHALCMEAPENATAGPAEPHKGLGMLPVAPRPARPPGDLGPGAGGSGT CENPEKFQYVEKSRSCAPRCGPGVEVFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRF QYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGALYVIQEGLENTGCTLVFLLLYYFGM ASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGLCYV ASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILY TVPATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVV GITSGVWVWSSKTFQTWQSLCYRKIAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSL ENPTHL

Function of FZD9 Membrane Protein

FZD9 is a Wnt2 receptor that is often associated with the β-catenin standard signal transduction pathway that activates the nuclear accumulation of disheveled proteins, β-catenin, and Wnt target genes. Inhibition of cell proliferation plays an important role in the induction of hsamiR29b by Wnt7a/Fzd9 signaling mediated by ERK5 and PPARγ. The expression of hsa-miR29b degrades MDM2 mRNA, eventually leading to increased p53 levels and reduced cell proliferation. However, in NSCLC, deletion of Wnt7a does not activate the Wnt7a/Fzd9 pathway that blocks the induction of hsa-miR29b expression. In general, loss or downregulation of hsa-miR29b expression leads to increased MDM2 levels, which reduce p53 expression and increase cell proliferation.

Fig.1 Schematic representation of the role of Wnt7a-induced hsa-miR29bexpression in NSCLC proliferation. (Avasarala, 2013)

Application of FZD9 Membrane Protein in Literature

Wang Q., et al. Involvement of c-Fos in cell proliferation, migration, and invasion in osteosarcoma cells accompanied by altered expression of Wnt2 and Fzd9. PLoS One. 2017, 96(1): 53-64. PubMed ID:28665975

This article reports that the expression of c-Fos, Wnt2 and Fzd9 proteins in human OS tissues was significantly higher than that of adjacent non-cancer tissues. Knockdown of c-Fos could inhibit the proliferation, migration,and invasion of MG63 cells, and promote the apoptosis of MG63 cells.
Ramírez V. T., et al. Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation. J Biol Chem. 2016, 291(36): 19092-107. PubMed ID: 27402827

This article reveals that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons.
Tennis M. A., et al. Prostacyclin reverses the cigarette smoke-induced decrease in pulmonary Frizzled 9 expression through miR-31. Sci Rep. 2016, 6: 28519. PubMed ID:27339092

The article pointed out that cigarette smoke exposure increased miR-31 expression, resulting in decreased expression of Fzd9, and to prevent the response to iloprost; when the removal of smoke, miR-31 decreased, prostacyclin can increase Fzd9 expression, inhibiting stunting progress.
Zhang Y., et al. Methylation status of the promoter region of the human frizzled 9 gene in acute myeloid leukemia. Mol Med Rep. 2016, 14(2):1339-44. PubMed ID:27314612

This article indicated that the methylation profile of the FZD9 gene corresponded to that of a candidate tumorsuppressor gene in acute myeloid leukemia.
Avilés E. C., et al. Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells. Front Cell Neurosci.2014, 8:110. PubMed ID:24860427

This article shows that the Wnt receptor Frizzled-9 (Fzd9) is expressed in developing skeletal muscle during NMJ synaptogenesis, and Fzd-mediated β-catenin-dependent signaling plays an important role in vertebrate NMJ assembly.

FZD9 Preparation Options

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Reference

Avasarala S, et al. (2013). hsa-miR29b, a critical downstream target of non-canonical Wnt signaling, plays an anti-proliferative role in non-small cell lung cancer cells via targeting MDM2 expression. Biology open, 2(7): 675-685.

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