Recombinant Human Forkhead box protein L2 (FOXL2)

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Code CSB-EP008827HU
Size $306
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 90% as determined by SDS-PAGE.
Target Names
FOXL2
Uniprot No.
Research Area
Others
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
1-376aa
Target Protein Sequence
MMASYPEPEDAAGALLAPETGRTVKEPEGPPPSPGKGGGGGGGTAPEKPDPAQKPPYSYVALIAMAIRESAEKRLTLSGIYQYIIAKFPFYEKNKKGWQNSIRHNLSLNECFIKVPREGGGERKGNYWTLDPACEDMFEKGNYRRRRRMKRPFRPPPAHFQPGKGLFGAGGAAGGCGVAGAGADGYGYLAPPKYLQSGFLNNSWPLPQPPSPMPYASCQMAAAAAAAAAAAAAAGPGSPGAAAVVKGLAGPAASYGPYTRVQSMALPPGVVNSYNGLGGPPAAPPPPPHPHPHPHAHHLHAAAAPPPAPPHHGAAAPPPGQLSPASPATAAPPAPAPTSAPGLQFACARQPELAMMHCSYWDHDSKTGALHSRLDL
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
43.8 kDa
Protein Length
Full Length
Tag Info
N-terminal 10xHis-tagged and C-terminal Myc-tagged
Form
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.
Buffer
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
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.
Lead Time
3-7 business days
Notes
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.
Description

The expression region of this recombinant Human FOXL2 covers amino acids 1-376. The expected molecular weight for the FOXL2 protein is calculated to be 43.8 kDa. Expression of this FOXL2 protein is conducted in e.coli. The FOXL2 coding gene included the N-terminal 10xHis tag and C-terminal Myc tag, which simplifies the detection and purification processes of the recombinant FOXL2 protein in following stages of expression and purification.

The human forkhead box protein L2 (FOXL2) is a transcription factor that plays a crucial role in various developmental processes, particularly in the development of ovarian tissues. FOXL2 is prominently expressed in ovarian granulosa cells, contributing to ovarian function and folliculogenesis. Mutations in the FOXL2 gene are associated with blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), a genetic disorder characterized by eyelid malformations and ovarian dysfunction in affected females. Beyond its developmental role, FOXL2 is implicated in maintaining granulosa cell identity and suppressing male-specific gene expression in ovarian tissues. Understanding FOXL2's functions is essential for unraveling the complexities of ovarian development and related genetic disorders.

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Target Background

Function
Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Prevents trans-differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9. Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen. Is a regulator of CYP19 expression. Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element. Is a transcriptional repressor of STAR. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2.
Gene References into Functions
  1. Thus, FOXL2C134W potentiates CYP19 expression in HGrC1 cells via enhanced recruitment of SMAD3 to a proximal FOX binding element. PMID: 29471425
  2. In the present study, we analysed two Han Chinese families with BPES type I and identified two novel mutations (c.462_468del and c.988_989insG). Immunofluorescence and confocal microscopy revealed that the extended FOXL2, p.Ala330Glyfs*204, induced significant mislocalization and aggregation. PMID: 29378385
  3. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic Atrial Septal Defect (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic Atrial Septal Defect (P<5x10-4). PMID: 29505555
  4. We describe a girl and her father with isolated BPES without an intragenic mutation in FOXL2. MLPA of a FOXL2 enhancer region identified a small microdeletion at 234 kb upstream of FOXL2. This deletion fully includes the PISRT1 gene, a noncoding gene which is part of a cis-regulatory element of FOXL2 PMID: 29481440
  5. MiR-937 inhibits the proliferation and metastasis of gastric cancer cells by targeting FOXL2 via inactivation of PI3K/AKT signaling pathway. These results suggest that miR-937 may be a potential target for the treatment of gastric cancer. PMID: 29060929
  6. This study demonstrated the existence of an AMH-FOXL2 relationship in hGCs. AMH is capable of increasing both gene and protein expression of FOXL2. Because FOXL2 induces AMH transcription, these ovarian factors could be finely regulated by a positive feedback loop mechanism to preserve the ovarian follicle reserve. PMID: 28660501
  7. A novel FOXL2 indel mutation was identified in Chinese families with BPES. Our results expand the spectrum of known FOXL2 mutations and provide additional insight into the structure-function relationships of the FOXL2 protein. PMID: 28924383
  8. The adult granulosa cell tumor (AGCT)-like components are likely to be tumor-like proliferations but not truly neoplastic AGCT. FOXL2 mutation testing may be useful in confirming an AGCT-like component. PMID: 27648785
  9. This novel duplicate mutation (c.844_860dup17, p.His291Argfs*71) in FOXL2 was identified in a Chinese family with both types of BPES. These findings expand current knowledge of the mutation spectrum of the FOXL2 gene and confirmed the intrafamily phenotypic heterogeneity of BPES. PMID: 28849110
  10. The study shows that half of granulosa theca cell tumors harbor the same FOXL2 mutation that characterizes adult granulosa cell tumors but there is no outcome evidence to guide whether mutation status should alter the classification of the tumor or the management of the patient. PMID: 28319575
  11. The promoter of FOXL2 was successfully cloned and registered in Gen Bank, and a dual luciferase reporter (DLR) analysis demonstrated that the luciferase activity was significantly induced by the promoter of FOXL2. Subsequently, bioinformatics analysis indicated that FOXL2 may be regulated by STAT3. PMID: 28677787
  12. This study demonstrated that the transactivation of FOXL2 driven by interactions between HMGA2 and pRb might exert critical effects on the metastases and EMT of chemoresistant gastric cancer. Blocking the HMGA2-FOXL2-ITGA2 pathway could serve as a new strategy for gastric cancer treatment. PMID: 28119367
  13. A novel deletion mutation (C.634_641 del, CCCATGC) between the forkhead domain and the polyalanine domain was found, resulting in a frameshift mutation and a truncated protein. PMID: 29339661
  14. FOXL2 had a sensitivity and specificity of 100% for all the cases of sex cord stromal tumors included in this study PMID: 28272677
  15. Our results suggest that, in contrast to FOXL2 mutations in adult granulosa cell tumours (A-GCTs), DICER1 mutations in Sertoli-Leydig cell tumours (SLCTs) might be more useful for prognosis than for diagnosis. PMID: 26033501
  16. Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of Uterine tumor resembling ovarian sex cord tumor (UTROSCT). PMID: 26598979
  17. This report describes the preservation of heterozygous c.402C>G FOXL2 mutation in recurrent aGCTs. This finding adds further credence to the concept that the c.402C>G FOXL2 mutation is oncogenic and integral to this disease. PMID: 28594898
  18. The novel mutations of the FOXL2 are associated with blepharophimosis, ptosis and epicanthus inversus syndrome. PMID: 28604951
  19. this study identified a novel regulatory circuit for ovarian AMH production; specifically, through the coordinated interplay between FOXL2 and SF-1 that could control ovarian follicle development. PMID: 27414805
  20. we report the identification of two novel and two recurrent heterozygous NOBOX variants in 7 out of 107 patients, with a prevalence of 6.5% (upper 95% confidence limit of 11.17%). Several variants conserve the ability to interact with FOXL2 in intracellular aggregates PMID: 27798098
  21. This is the first study reporting lacrimal gland(LG) volumes in BPES, describing a significant number of patients with LG agenesis. Molecular analysis of the FOXL2 gene revealed the presence of 8 distinct mutations. PMID: 27914838
  22. In the case of aGCT, a well characterized mutation in the FOXL2 transcription factor (FOXL2 C134W) is found in almost all cases, which arguably defines the disease, although the molecular events that determine the stage, behavior and prognosis of aGCT remain to be determined. PMID: 27813081
  23. We highlight the cooperation of WNT4, RSPO1 and FOXL2 within a regulatory network and the need for further research to better understand their role in defining and maintaining ovarian identity. PMID: 27604691
  24. The de novo mutation rate in FOXL2 is exceptionally high compared with other dominant disorders manifesting with an ocular phenotype. PMID: 27283035
  25. SUMOylation of FOXL2 and PML Bodies PMID: 22022399
  26. Ten novel protein partners of FOXL2 PMID: 22544055
  27. FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells PMID: 25369636
  28. The absence of FOXL2 and DICER1 gene mutation observed in 3 patients, along with strong FOXL2 immunoreactivity provides additional evidence to place microcystic stromal tumor within pure gonadal stromal rather than sex cord ovarian tumors. PMID: 27830327
  29. genetic association study in two families with blepharophimosis-ptosis-epicanthus inversus syndrome type 1: Two distinct mutations, a missense p.H104R change and an in-frame p.A222_A231dup10 duplication in FOXL2 gene are identified in three women. PMID: 26100530
  30. suggests the potential of pS33 FOXL2 to serve as a new biomarker for the diagnosis of adult-type GCT PMID: 25871347
  31. Our combined analysis identifies potential candidate genes, whose alterations might contribute to adult-type Ovarian granulosa cell tumors formation/progression together with the recurrent FOXL2 somatic mutation. PMID: 25884336
  32. Foxl2 deletion in either Cranial Neural Crest Cells (CNCCs) or Cranial Mesodermal Cells (CMCs) prevents eyelid closure and induces subtle skeletal developmental defects. PMID: 25416281
  33. C134W mutation affects granulosa cell tumor development via differential posttranslational modifications of FOXL2 by GSK3B. PMID: 24390485
  34. Two novel FOXL2 mutations (c.675_690delinsT, and p.Leu75Phe) were identified in Chinese families with blepharophimosis-ptosis-epicanthus inversus syndrome. PMID: 26323275
  35. Uterine tumors resembling ovarian sex cord tumors do not harbor FOXL2 mutation PMID: 25581731
  36. FOXL2 p.C134W mutation-positive adult-type granulosa cell tumor of the ovary may not be common in the Japanese. PMID: 24689977
  37. report the 402C-->G FOXL2 mutation status in five epithelial ovarian lesions in women aged 45-77 years showing stromal proliferations that were morphologically indistinguishable from adult granulosa cell tumour PMID: 24138090
  38. FOXL2 mRNA is hyperexpressed in the endometrium in endometriosis. PMID: 24520083
  39. both NOBOX and FOXL2 are expressed in human follicle granulosa cells and their interaction plays an inhibitory role in the transcriptional response of these promoters. PMID: 24620032
  40. Mouse Foxl2 expression is downregulated by mir-133a. PMID: 25317675
  41. FOXL2 suppresses proliferation, invasion and promotes apoptosis of cervical cancer cells. PMID: 24817949
  42. The authors describe a boy with blepharophimosis syndrome plus from a de novo heterozygous 3q22.3-q24 11.2 Mb microdeletion. PMID: 25032695
  43. decreased apoptotic and antiproliferative activities caused by mutant forms of FOXL2 found in blepharophimosis-ptosis-epicanthus inversus syndrome patients may at least partially contribute to the pathophysiology of ovarian dysfunction. PMID: 24240106
  44. In this review, we focus on the role of four specific FOX factors (FOXD1, FOXL2, FOXO1 and FOXP3) in gonadotropin hormone production PMID: 24099863
  45. investigated the impact of FOXL2 point mutation testing in a large cohort of adult-type granulosa cell tumours of the ovary PMID: 24192202
  46. The molecular interactions of FOXL2, GATA4, and SMAD3 and their roles in the regulation of CCND2 using co-immunoprecipitation, promoter transactivation, and cell viability assays in human granulosa cell tumor cells, were investigated. PMID: 24416423
  47. a FOXL2 mutation (c.402C>G) may have a role in development of adult-type ovarian granulosa cell tumors in Japanese patients PMID: 24257635
  48. The 402C>G mutation in FOXL2, found in adult ovarian granulosa cell tumors, appears to deregulate the anti-proliferative TGF-beta pathway. Mutant FOXL2's inability to elicit an apoptotic signal cascade may be important in pathogenesis. [Review Article] PMID: 24342437
  49. FOXL2 is expressed in normal ovaries and ovarian sex cord stromal tumors, is also expressed in ovarian-type stroma characteristic of pancreatic mucinous cystic neoplasms, hepatobiliary cystadenomas, and mixed epithelial and stromal tumor of the kidney . PMID: 24746205
  50. We investigated the mechanism by which Notch1 activation controls expression of FoxL2, which in turn activates smooth muscle actin gene expression in periocular mesenchyma to control eyelid levator smooth muscle formation. PMID: 23084143

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Involvement in disease
Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES); Premature ovarian failure 3 (POF3)
Subcellular Location
Nucleus.
Tissue Specificity
In addition to its expression in the developing eyelid, it is transcribed very early in somatic cells of the developing gonad (before sex determination) and its expression persists in the follicular cells of the adult ovary.
Database Links

HGNC: 1092

OMIM: 110100

KEGG: hsa:668

STRING: 9606.ENSP00000333188

UniGene: Hs.289292

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