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  4. Recombinant Human Frizzled-4 (FZD4)

Recombinant Human Frizzled-4 (FZD4)

  • 中文名称：
    人FZD4重组蛋白
  • 货号：
    CSB-CF890755HU
  • 规格：
  • 来源：
    in vitro E.coli expression system
  • 其他：

产品详情

  • 基因名：
  • Uniprot No.：
  • 别名：
    FZD4; Frizzled-4; Fz-4; hFz4; FzE4; CD antigen CD344
  • 种属：
    Homo sapiens (Human)
  • 蛋白长度：
    Full Length of Mature Protein
  • 表达区域：
    37-537
  • 氨基酸序列
    FGDEEERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQF FLCSVYVPMCTEKINIPIGPCGGMCLSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNH MCMEGPGDEEVPLPHKTPIQPGEECHSVGTNSDQYIWVKRSLNCVLKCGYDAGLYSRSAK EFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVG RERISCDFEEAAEPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWG HEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELTGLCYVGNQNLDALTGFVVAPLF TYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVIACYF YEISNWALFRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNRLVNSGK VKREKRGNGWVKPGKGSETVV
    Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
  • 蛋白标签：
    N-terminal 10xHis-tagged
  • 产品提供形式：
    Liquid or Lyophilized powder
    Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
  • 缓冲液：
    Lyophilized from Tris/PBS-based buffer, 6% Trehalose, pH 8.0
  • 储存条件：
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保质期：
    The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
    Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
  • 货期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
    Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
  • 注意事项：
    Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
  • Datasheet & COA：
    Please contact us to get it.

产品评价

靶点详情

  • 功能：
    Receptor for Wnt proteins. 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. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). 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. 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.
  • 基因功能参考文献：
    1. This is the first study to report a group of patients with digenic familial exudative vitreoretinopathy (FEVR). In most affected eyes, the stage was more severe than stage 3. We speculate that the phenotype of FEVR is more severe in patients with digenic rather than monogenic variants of FEVR-related genes. PMID: 30097784
    2. FzM1.8 is an allosteric agonist of FZD4. In the absence of any WNT ligand, FzM1.8 binds to FZD4, promotes recruitment of heterotrimeric G proteins, and biases WNT signaling toward a noncanonical route that involves PI3K. In colon cancer cells, the FZD4/PI3K axis elicited by FzM1.8 preserves stemness and promotes proliferation of undifferentiated cells. PMID: 29293331
    3. FZD4 Tyrosine 250(2.39) is crucial for DVL2 interaction and DVL2 translocation to the plasma membrane. PMID: 28668722
    4. Accessory proteins in Frizzled (FZD) receptor complexes are thought to determine ligand selectivity and signaling amplitude. PMID: 28658627
    5. FZD4 was confirmed to be a downstream target of miR-505, and found to be up-regulated in cervical cancer patients. PMID: 28577497
    6. The screening of candidate genes namely NDP, FZD4 and TSPAN12 led to the identification of six major coding region variants in 36 ROP probands. PMID: 28982955
    7. Seven novel mutations found in this study have broadened the spectrum of mutations in FZD4 known to cause familial exudative vitreoretinopathy (FEVR), providing a deeper understanding of this disease. The results show that mutations in FZD4 are associated with the phenotypes of retinal folds or ectopic macula in FEVR PMID: 27555740
    8. Three affected individuals within a family with FEVR presented with variable disease severity. All three affected family members harboured mutation c.349T>C (p.Cys117Arg) in FZD4. PMID: 28211206
    9. The findings in this family support the concept that some mutated FZD4 alleles can be associated with recessive rather than dominant disease. PMID: 27668459
    10. novel role of let-7b/Fzd4 axis through wnt signaling PMID: 27510711
    11. FZD4 down-regulation leads to loss of WNT/beta-catenin signal activity and subsequently to reduced alveolar epithelial cell wound repair capacity and impaired expression of elastogenic components. PMID: 28245136
    12. his study showed that Let7b modulates the proliferation, invasiveness, and migration of liver cancer cell and reduces the proportion of cancer stem cells in liver cancer cell by inhibiting Wnt/beta-catenin signaling pathway via downregulated Frizzled4. PMID: 28671046
    13. Among the detected mutations, LRP5 accounted for the largest proportion with a mean mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31, 6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were predicted to be pathogenic by a series of bioinformatics analyses. PMID: 28494495
    14. human FZD4 assembles-in a DVL-independent manner-with Galpha12/13 but not representatives of other heterotrimeric G protein subfamilies. PMID: 27458145
    15. Several novel mutations (missense, non-stop and insertion) were detected in the coding regions of FZD4, TSPAN12 and ZNF408 genes among the unrelated familial exudative vitreoretinopathy probands. The mutations in FZD4 and TSPAN12 were involved in autosomal dominant and autosomal recessive families and further validates the involvement of these gene in exudative vitreoretinopathy development. PMID: 27316669
    16. Two were novel mutations: p.E134* and p.T503fs of FZD4 lead to the loss of FZD4 activity. PMID: 26530129
    17. Letter: FZD4+ and FZD4- melanocytes were significantly lower in hair follicles of patients with rhododenol-induced leukoderma. PMID: 26277630
    18. These structural, biophysical and cellular data, map Fz4 and putative Lrp5/6 binding sites to distinct patches on Norrin, and reveal a GAG binding site spanning Norrin and Fz4 cysteine-rich domain. PMID: 26158506
    19. The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP (retinopathy of prematurity) and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth. PMID: 26119001
    20. Mutations of FZD4 accounted for the largest proportion, which could be directly applied to the testing strategy to start with screening for FZD4 mutations. PMID: 26244290
    21. analysis of allosteric ligands of Frizzled4 PMID: 25751279
    22. Defective trafficking resulting in haploinsufficiency is a major cellular mechanism for several missense FEVR-causing FZD4 mutants. PMID: 24744206
    23. Six different nonsynonymous DNA variants are identified in the coding region of either the FZD4 gene (p.H69Y, p.R127H, and p.Y211H) or the LRP5 gene (p.R1219H, p.H1383P, and p.T1540M) in seven patients with advanced retinopathy of prematurity PMID: 23441120
    24. Five mutations have been found in the FZD4 gene in six Chinese families with familial exudative vitreoretinopathy. PMID: 23077402
    25. Genetic analysis revealed that all affected family members of one pedigree carried an exon 2 mutation of COL2A1, and in the second pedigree, all affected members carried an FZD4 mutation. PMID: 22574936
    26. miR-493 is a new tumor suppressor miRNA in bladder cancer and inhibits cell motility through downregulation of RhoC and FZD4. PMID: 22057916
    27. Frizzled 4 is a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and that it may be a major cause of GBM recurrence and poor prognosis. PMID: 21363911
    28. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of familial exudative vitreoretinopathy & Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease. PMID: 21097938
    29. The profile of the mutations obtained in FZD4 further illustrates the complexity of familial exudative vitreoretinopathy (FEVR)and provides a better understanding of the genotype-phenotype correlations. PMID: 20938005
    30. Results provide mechanistic insights to ERG oncogenesis in prostate cancer, involving activation of WNT signaling through FZD4, leading to cancer-promoting phenotypic effects, including EMT and loss of cell adhesion. PMID: 20713528
    31. Studies report 21 novel variants for FZD4, LRP5, and NDP. PMID: 20340138
    32. Mutations in the FZD4 gene in this group of premature infants supports a role for the FZD4 pathway in the development of severe retinopathy of prematurity. PMID: 20141357
    33. Functions in retinal angiogenesis. Mutations disrupts angiogenesis in vitreoretinopathy. PMID: 12172548
    34. High-resolution genotyping and haplotype analysis excluded FZD4 as the defective gene in a family previously linked to the EVR1 locus. PMID: 14737064
    35. Familial exudative vitreoretinopathy has mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor PMID: 15024691
    36. Eight mutations have been identified in the FZD4 gene in a cohort of 40 unrelated patients with FEVR (familial exudative vitreoretinopathy) PMID: 15223780
    37. FZD4 mutations are associated with autosomal dominant familial exudative vitreoretinopathy PMID: 15370539
    38. A novel missense mutation in the FZD4 gene was identified in Japanese patients with FEVR (familial exudative vitreoretinopathy). PMID: 15488808
    39. mutations in the LRP5 and/or FZD4 genes may have roles in familial exudative vitreoretinopathy PMID: 15981244
    40. Mutations in FZD4 were observed in 5.6% of studied clinically diagnosed familial exudative vitreoretinopathy in Indian population. Could play vital role in pathogenesis and provide greater insight in to genotype/phenotypic functions of FZD4 gene. PMID: 17093393
    41. Fz4 expression may play a critical role in responses to Wnt signaling in the tumor microenvironment. PMID: 17386109
    42. sFRP-1 can interact with Wnt receptors Frizzled 4 and 7 on endothelial cells to transduce downstream to cellular machineries requiring Rac-1 activity in cooperation with GSK-3beta PMID: 18156211
    43. Homozygous state for the FZD4 gene is possibly involved in the severity of the familial exudative vitreoretinopathy phenotype PMID: 18161623
    44. Report activation of Wnt signalling in acute myeloid leukemia by induction of Frizzled-4. PMID: 19020754
    45. The clinical features in the three children and their relatives with a documented FZD4 mutation support the previous reports of a high degree of intrafamilial and interfamilial variability in familial exudative vitreoretinopathy (FEVR). PMID: 19172507
    46. Mutations occurring in the FZD4 gene affect patients diagnosed with both autosomal-dominant familial exudative vitreoretinopathy (AdFEVR) or retinopathy of prematurity (ROP) PMID: 20008721

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  • 相关疾病：
    Vitreoretinopathy, exudative 1 (EVR1)
  • 亚细胞定位：
    Cell membrane; Multi-pass membrane protein.
  • 蛋白家族：
    G-protein coupled receptor Fz/Smo family
  • 组织特异性：
    Almost ubiquitous. Largely expressed in adult heart, skeletal muscle, ovary, and fetal kidney. Moderate amounts in adult liver, kidney, pancreas, spleen, and fetal lung, and small amounts in placenta, adult lung, prostate, testis, colon, fetal brain and l
  • 数据库链接：

    HGNC: 4042

    OMIM: 133780

    KEGG: hsa:8322

    STRING: 9606.ENSP00000434034

    UniGene: Hs.591968