Recombinant Human RSPO1 Protein (His Tag)
Beta LifeScience
SKU/CAT #: BLPSN-4097
Recombinant Human RSPO1 Protein (His Tag)
Beta LifeScience
SKU/CAT #: BLPSN-4097
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Product Overview
Tag | His |
Host Species | Human |
Accession | NP_001033722.1 |
Synonym | CRISTIN3, R-Spondin 1, RSPO |
Background | RSPO1 gene is a member of the R-spondin family. It encodes RSPO1 which is known as a secreted activator protein with two cystein-rich, furin-like domains and one thrombospondin type 1 domain. In mice, RSPO1 induces the rapid onset of crypt cell proliferation and increases intestinal epithelial healing, providing a protective effect against chemotherapy-induced adverse effects. This protein is an activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. RSPO1 acts both in the canonical Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway, probably by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. It also acts as a ligand for frizzled FZD8 and LRP6. |
Description | A DNA sequence encoding the human RSPO1 (NP_001033722.1) (Met 1-Ala 263) was expressed, fused with a His tag at the C-terminus. |
Source | HEK293 |
Predicted N Terminal | Ser 21 |
AA Sequence | Met 1-Ala 263 |
Molecular Weight | The secreted recombinant human RSPO1 comprises 254 a.a. with a predicted molecular mass of 28.2 kDa. As a result of glycosylation, rhRSPO1 migrates as an approximately 42 kDa band in SDS-PAGE under reducing conditions. |
Purity | >95% as determined by SDS-PAGE |
Endotoxin | < 1.0 EU per μg of the protein as determined by the LAL method |
Bioactivity | 1. Measured by its binding ability in a functional ELISA. Immobilized human RSPO1 at 20 ug/ml (100 ul/well) can bind human LIMPII with a linear ranger of 32-800 ng/ml.2. Measured by its binding ability in a functional ELISA. Immobilized human RSPO1 at 20 ug/ml (100 ul/well) can bind mouse CD36 with a linear ranger of 6.4-800 ng/ml.3. Measured by its ability to induce activation of βcatenin response in a Topflash Luciferase assay using HEK293T human embryonic kidney cells. The ED50 for this effect is typically 0.1-0.9 ug/mL in the presence of 5 ng/mL recombinant mouse Wnt3a. |
Formulation | Lyophilized from sterile PBS, pH 7.4. |
Stability | The recombinant proteins are stable for up to 1 year from date of receipt at -70°C. |
Usage | For Research Use Only |
Storage | Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles. |
Target Details
Target Function | Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination. Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1. |
Subcellular Location | Secreted. Nucleus. |
Protein Families | R-spondin family |
Database References | |
Associated Diseases | Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC) |
Tissue Specificity | Abundantly expressed in adrenal glands, ovary, testis, thyroid and trachea but not in bone marrow, spinal cord, stomach, leukocytes colon, small intestine, prostate, thymus and spleen. |
Gene Functions References
- first report of a RSPO1 missense mutation in association with human disease (familial 46,XX disorder of sexual development) . PMID: 29262419
- Rspo1 increases the number of Lgr5(+) liver stem cells in human liver fibrosis tissues, and once they are isolated, these cells are able to form organoids, and treatment with HGF/Rspo1 promotes their expansion PMID: 29079780
- RSPOs facilitate HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway PMID: 27572318
- Role of RSPO1 in gastric cancer PMID: 28219935
- Results showed that Rspo1 expression is downregulated in adult follicles but its activation is sufficient in promoting ovarian tumors supporting its direct involvement in the initiation of ovarian cancers. PMID: 27270435
- 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
- Rspo1 glycosylation at Asn137 is essential for secretion and stability but not for heparin binding. PMID: 27314333
- DPY19L3-mediated C-mannosylation of Rspo1 at tryptophan(156) is required for Rspo1 secretion. PMID: 26764097
- Genetic variants in ZC3H11B, RSPO1, and GJD2 are associated with susceptibility to the development of high myopia in a Han Chinese population. PMID: 26485405
- R-Spondin1 has an effect on radiosensitivity of glioma cells PMID: 25865226
- ZNRF3 and LGR4-binding sites in RSPO1 are required for Wnt signaling. PMID: 24165923
- Changes in the expression levels of IRS1, IRS2, RIPK2, RSPO1, and DNA JC15 genes might contribute to the development of insulin resistance and glucose intolerance in the obese boys. PMID: 26040030
- the LGR4-Rspo1 complex crystal structure shows divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors PMID: 25480784
- ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain. PMID: 24349440
- overexpressed in fibrotic liver tissue PMID: 25218283
- Loss of RSPO1 expression is associated with invasive ductal carcinoma of the breast. PMID: 24373193
- RSPO-LGR4 not only induces the clearance of RNF43/ZNRF3 to increase Wnt receptor levels but also recruits IQGAP1 into the Wnt signaling complex. PMID: 24639526
- Crystal structures of the Lgr4 ectodomain alone and bound to Rspo1. PMID: 23891289
- In conclusion, present study highlights the role of Rspo 1 in bone remodeling where it activates Wnt signaling to induce differentiation, as shown in human as well murine in vitro osteoblast cell models. PMID: 23617070
- Recent developments have demonstrated that ovarian development is an active process (rather than a default process); ovarian development/function requires expression of RSPO1, WNT4, and FOXL2. [REVIEW] PMID: 23044875
- R-Spondin potentiates Wnt/beta-catenin signaling through orphan receptors LGR4 and LGR5 PMID: 22815884
- study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration PMID: 22575959
- R-spondin1 is upregulated during critical stages of early human ovary development and may function as a tissue-specific amplifier of beta-catenin signaling to oppose testis determination. PMID: 21297984
- identified a gene, R-spondin1, with potent and specific proliferative effects on intestinal crypt cells PMID: 16109882
- Human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. PMID: 17041600
- RSPO1 regulates Wnt signaling by inhibiting internalization of LRP6. PMID: 17804805
- Mutational analysis of the RSPO1 gene in a 46,XX woman with true hermaphroditism, palmoplantar keratoderma, congenital bilateral corneal opacities, onychodystrophy, and hearing impairment, is reported. PMID: 18085567
- R-sponin1 (Rspo1) acted synergistically with Wnt3A to activate Wnt/beta-catenin signaling in the uncommitted mesenchymal C2C12 cells. PMID: 18242177
- SRY represses the transcriptional of the Rspo1/Wnt target genes involved in ovarian determination. PMID: 19376480
- Mice treated with R-spondin1 showed increased intestinal epithelial healing, providing a protective effect against chemotherapy-induced intestinal mucositis. PMID: 16306530