Recombinant Human Sonic Hedgehog / SHH Protein (aa 1-197, His Tag)

Beta LifeScience SKU/CAT #: BLPSN-4308

Recombinant Human Sonic Hedgehog / SHH Protein (aa 1-197, His Tag)

Beta LifeScience SKU/CAT #: BLPSN-4308
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Product Overview

Tag His
Host Species Human
Accession Q15465
Synonym HHG1, HLP3, HPE3, MCOPCB5, SMMCI, Sonic hedgehog, TPT, TPTPS
Background Sonic HedgeHog, also known as sonic hedgehog protein, belongs to the hedgehog family. It cannot be detected in adult tissues while can be found in fetal intestine, liver, lung, and kidney. Sonic HedgeHog is a protein that is vital in guding the early embryo. It has been associated as the major inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Sonic HedgeHog intercellular signal is essential for a various patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Sonic HedgeHog binds to the patched receptor, which functions in association with smoothened, to activate the transcription of target genes. In the absence of sonic HedgeHog, patched receptor represses the constitutive signaling activity of smoothened. Sonic HedgeHog also regulates another factor, the gli oncogene. Defects in sonic hedgehog can cause microphthalmia isolated with coloboma type 5, triphalangeal thumb-polysyndactyly syndrome and holoprosencephaly type 3.
Description A DNA sequence encoding the amino acid sequence (Met 1-Gly 197) of human SHH (Q15465), that is Sonic hedgehog protein N-product, was fused with a His tag at the C-terminus.
Source HEK293
Predicted N Terminal Cys 24
AA Sequence Met 1-Gly 197
Molecular Weight The recombinant human SHH (aa 1-197) consists of 185 a.a. and has a predicted molecular mass of 21 kDa. The apparent molecular mass of the protein is approximately 24 kDa in SDS-PAGE under reducing conditions due to glycosylation.
Purity >95% as determined by SDS-PAGE
Endotoxin < 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity Measured by its ability to induce alkaline phosphatase production by C3H10T1/2 mouse embryonic fibroblast cells. Nakamura, T. et al. (1997) Biochem. Biophys. Res. Commun.237:465.The ED50 for this effect is typically 2-10 ug/mL.
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 The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity. Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN. Both activities occur in the reticulum endoplasmic. Once cleaved, ShhC is degraded in the endoplasmic reticulum.; The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites. Involved in the patterning of the anterior-posterior axis of the developing limb bud. Essential for axon guidance. Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO.
Subcellular Location Endoplasmic reticulum membrane. Golgi apparatus membrane.; [Sonic hedgehog protein N-product]: Cell membrane; Lipid-anchor.
Protein Families Hedgehog family
Database References
Associated Diseases Microphthalmia, isolated, with coloboma, 5 (MCOPCB5); Holoprosencephaly 3 (HPE3); Solitary median maxillary central incisor (SMMCI); Triphalangeal thumb-polysyndactyly syndrome (TPTPS); Preaxial polydactyly 2 (PPD2); Hypoplasia or aplasia of tibia with polydactyly (THYP); Laurin-Sandrow syndrome (LSS)

Gene Functions References

  1. The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. PMID: 28496132
  2. Disturbed SHH link between KIF7 and C5orf42 contributes to neurodevelopmental features characteristic of C5orf42-related ciliopathies. PMID: 29321670
  3. Histone deacetylase 6 (HDAC6) inhibition enhanced glioma stem cells (GSCs) radiosensitivity via inactivating sonic hedgehog protein (SHH)/glioma-associated oncogene homolog 1 (Gli1) pathway. PMID: 29222038
  4. Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells PMID: 29734730
  5. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. PMID: 29954986
  6. Protease nexin-1 prevents growth of human B cell lymphoma via inhibition of sonic hedgehog signaling. PMID: 29483508
  7. SHH-related signaling pathway affects antineoplastic drug resistance in cultured glioma cells. PMID: 29313231
  8. SHH is expressed in cilia in the airway epithelial cells.SHH may mediate noncanonical hedgehog signaling through motile cilia to dampen respiratory defenses. PMID: 29358407
  9. High SHH expression is associated with radioresistance in esophageal adenocarcinoma. PMID: 29715275
  10. Identify SMO-dependent Shh signalling as a specific process for the activation of adventitial fibroblasts and the subsequent proliferation of smooth muscle cells and neointima formation. PMID: 29088375
  11. In conclusion, our data suggest that overexpression of the Hedgehog components SHH, GLI2 and FOXA2 might be used as markers of an aggressive hemangioma. PMID: 28370639
  12. These findings showed the upexpression of sonic hedgehog and vascular endothelial growth factor with co-localization in varicocele veins which imply that the reducing hypoxia or using sonic hedgehog antagonists may be helpful for this vascular disease. PMID: 26867642
  13. Shh and Gli1 expression were associated with lymph node metastasis, TNM stage and tumor recurrence, suggesting Shh and Gli1 protein could become the valuable biomarker in evaluating the lymph node metastasis in oral squamous cell carcinoma. PMID: 28886265
  14. Epithelial-mesenchymal transition programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling. PMID: 29158396
  15. Case Report: medullablastoma with activated SHH expression. PMID: 29517209
  16. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous buildup (scar tissue) and inflammation of the liver tissue. For the first time patients with holoprosencephaly, a disease caused by SHH signaling mutations, are shown to have increased liver steatosis independent of obesity. PMID: 28645738
  17. Gpr161 is a critical factor in the basal suppression machinery of Shh signaling, neural tube morphogenesis and closure. (Review) PMID: 27731925
  18. Oncogenic activation of SHH is associated with Rubinstein-Taybi Syndrome and Medulloblastoma. PMID: 29551561
  19. The results showed that Shh and Gli1 were upregulated in prostate cancer tissues and were targeted by a phytogenic neoplastic compound carnosol. PMID: 28886322
  20. Hh signaling activation might reflect aggressive tumoral behavior, since high epithelial GLI2 expression positively correlates with a higher pathological Gleason score. Moreover, higher epithelial GLI3 expression is an independent marker of a more favorable prognosis. PMID: 28877722
  21. GPT2 reduced alpha-ketoglutarate level in cells leading to the inhibition of proline hydroxylase 2 (PHD2) activity involved in the regulation of HIF1alpha stability. Accumulation of HIF1alpha, resulting from GPT2-alpha-ketoglutarate-PHD2 axis, constitutively activates sonic hedgehog (Shh) signaling pathway. PMID: 28839461
  22. Results show SHH proteolysis is under the mechanism of Scube2 which is enriched at the surface of Shh-producing cells by heparan sulfate proteoglycans. PMID: 27199253
  23. influences sweat gland differentiation of stem cells PMID: 27120089
  24. during Hedgehog signaling, ligand binding inhibits Patched by trapping it in an inactive conformation, a mechanism that explains the dramatically reduced activity of oncogenic Patched1 mutants. PMID: 27647915
  25. In an in vitro model of LPS inflammation of the blood-brain barrier, sonic hedgehog signaling was activated by Wip1 overexpression and inhibited by silencing. Wip1 may protect the BBB against LPS damage via SHH signaling. PMID: 29128669
  26. the effect gene of the Shh pathway, gli1, was found to have a reduced level of expression along with a decreased expression of gli2. PMID: 26446020
  27. SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway PMID: 27289556
  28. Findings suggest that oral squamous cell carcinoma (OSCC)derived sonic hedgehog protein (SHH) stimulates angiogenesis at the tumor invasive front. PMID: 29187450
  29. Expression of SHH and GLI1 may be useful prognostic markers of Merkel cell carcinoma because increased expression was associated with better prognosis. PMID: 28551328
  30. High SHH expression is associated with esophageal squamous cell carcinoma. PMID: 29054489
  31. Studies suggest significance of other signaling aside from hedgehog in the pathogenesis of basal cell carcinoma (BCC) of the skin. PMID: 28574612
  32. Gorlin syndrome-derived induced pluripotent stem cells (iPSCs) expressed lower basal levels than control iPSCs of the genes encoding the Hh ligands Indian Hedgehog (IHH) and Sonic Hedgehog (SHH). PMID: 29088246
  33. SHH activation is associated with Rhabdomyosarcoma. PMID: 28881358
  34. Studies suggest that embryonic signaling pathways, the likes of Notch, Wnt, and Hedgehog and tumor marker Oct-4 offer targets for cascade-specific molecular inhibition as they are fundamental to (cancer and normal) stem cell maintenance and growth. PMID: 27730468
  35. Methylation at K436 and K595 respectively by Set7 increases the stability and DNA binding ability of Gli3, resulting in an enhancement of Shh signaling activation. PMID: 27146893
  36. Altogether, these data suggested that curcumin inhibited the activities of BCSCs through suppressing Shh pathway, which might be an effective chemopreventive agent for bladder cancer intervention. PMID: 28870814
  37. High SHH expression is associated with Small Cell Lung Cancer. PMID: 28870922
  38. Accumulating evidence suggest that cytochrome P450 (CYP26), the primary retinoid-inactivating enzyme, plays a critical role in the integration of two neoplastic molecular programs: the retinoid metabolism and Hedgehog pathways. (Review) PMID: 28754309
  39. CHSY1 overexpression in HCC contributes to the malignant behavior of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway. PMID: 28652022
  40. We found a novel 7q36.3 duplication involving 2 genes (SHH and RBM33) in a patient with complete corpus callosum agenesis (Figure), moderate learning difficulties, and macrocephaly PMID: 28284480
  41. Study showed that SHH expression was significantly high among breast cancer patients with advanced tumor grade, stage, nodal involvement and metastasis and this expression strongly correlated with proliferation marker. PMID: 28739739
  42. This suggests an important cross-talk between SHH and WIP1 pathways that accelerates tumorigenesis and supports WIP1 inhibition as a potential treatment strategy for MB. PMID: 27086929
  43. YB-1 is induced by Shh in CGNPs PMID: 26725322
  44. SHH siRNA synergistically enhanced cytotoxicity induced by itraconazole in MCF-7 cells. PMID: 27810405
  45. Hedgehog pathway activation in T-cell acute lymphoblastic leukemia predicts response to SMO and GLI1 inhibitors. PMID: 27694322
  46. Data suggest that negative feedback mediated by GLI3 (GLI-Kruppel family member) acts to finely tune SHH (sonic hedgehog) signaling. During medulloblastoma (MB) formation, nerve tissue cells appear to express nestin which hyperactivates SHH signaling by abolishing negative feedback by GLI3. Restoration of intrinsic negative feedback by repressing nestin expression represents a promising approach to treat MB. [REVIEW] PMID: 28389227
  47. The study reveals several novel individual and repetitive mutations of SHH gene in Gallbladder Cancer and Cholelithiasis samples that may be used as diagnostic markers for gallbladder carcinogenesis. PMID: 28058596
  48. Data indicate that agedunin induces its anti-metastatic effect through inhibition of sonic hedgehog protein [SHH] signaling. PMID: 26988754
  49. findings suggest that Usp7 is important for MB cell proliferation and metastasis by activating Shh pathway, and is a putative therapeutic target for MBs PMID: 28137592
  50. importance of MAOA for initiating the pre-metastatic niche in stromal cells and promoting PCa metastasis to bone and visceral organs, mediated by activation of paracrine Shh-IL6-RANKL signaling underlying tumor-stromal interactions. PMID: 28292438


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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

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