Recombinant Human SHH Protein

Name: Recombinant Human SHH Protein
Brand: Beta LifeScience
SKU: BL-1700SG
Availability: InStock

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Product Overview

Tag	N/A
Host Species	Human
Accession	Q15465
Synonym	SHH, HHG-1, Recombinant Human Sonic Hedgehog (SHH)
Background	Highly conserved proteins, members of the Hedgehog family are widely represented throughout the animal kingdom. The three known mammalian Hedgehog proteins; Sonic (SHH), Desert (DHH) and Indian (IHH) hedgehog share a high degree of sequence and structural identity. SHH is specifically known to be expressed in fetal intestine, liver, lung and kidney. Recombinant Human SHH represents the N-product (N-terminal domain with Cys24 substituted by an Ile-Val-Ile sequence) which retains all the known signalling capabilities.
Description	Recombinant Human SHH was produced in E. coli. This protein is purified with our unique purification methods.
Source	E.coli
Molecular Weight	20.1 kDa
Purity	For specific purity information on a given lot, see related COA.
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Formulation	Recombinant protein is supplied in 50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM Glutathione, 0.25mM DTT, 0.1mM EDTA, 0.1mM PMSF and 25% glycerol.
Stability	The recombinant protein is stable for up to 12 months at -70°C
Usage	For Research Use Only
Storage	Recombinant Human SHH Protein should be stored should be stored at < -70°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	HGNC: 10848 OMIM: 135750 KEGG: hsa:6469 STRING: 9606.ENSP00000297261 UniGene: PMID: 28496132 Disturbed SHH link between KIF7 and C5orf42 contributes to neurodevelopmental features characteristic of C5orf42-related ciliopathies. PMID: 29321670 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 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 Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. PMID: 29954986 Protease nexin-1 prevents growth of human B cell lymphoma via inhibition of sonic hedgehog signaling. PMID: 29483508 SHH-related signaling pathway affects antineoplastic drug resistance in cultured glioma cells. PMID: 29313231 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 High SHH expression is associated with radioresistance in esophageal adenocarcinoma. PMID: 29715275 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 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 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 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 Epithelial-mesenchymal transition programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling. PMID: 29158396 Case Report: medullablastoma with activated SHH expression. PMID: 29517209 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 Gpr161 is a critical factor in the basal suppression machinery of Shh signaling, neural tube morphogenesis and closure. (Review) PMID: 27731925 Oncogenic activation of SHH is associated with Rubinstein-Taybi Syndrome and Medulloblastoma. PMID: 29551561 The results showed that Shh and Gli1 were upregulated in prostate cancer tissues and were targeted by a phytogenic neoplastic compound carnosol. PMID: 28886322 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 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 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 influences sweat gland differentiation of stem cells PMID: 27120089 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 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 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 SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway PMID: 27289556 Findings suggest that oral squamous cell carcinoma (OSCC)derived sonic hedgehog protein (SHH) stimulates angiogenesis at the tumor invasive front. PMID: 29187450 Expression of SHH and GLI1 may be useful prognostic markers of Merkel cell carcinoma because increased expression was associated with better prognosis. PMID: 28551328 High SHH expression is associated with esophageal squamous cell carcinoma. PMID: 29054489 Studies suggest significance of other signaling aside from hedgehog in the pathogenesis of basal cell carcinoma (BCC) of the skin. PMID: 28574612 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 SHH activation is associated with Rhabdomyosarcoma. PMID: 28881358 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 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 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 High SHH expression is associated with Small Cell Lung Cancer. PMID: 28870922 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 CHSY1 overexpression in HCC contributes to the malignant behavior of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway. PMID: 28652022 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 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 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 YB-1 is induced by Shh in CGNPs PMID: 26725322 SHH siRNA synergistically enhanced cytotoxicity induced by itraconazole in MCF-7 cells. PMID: 27810405 Hedgehog pathway activation in T-cell acute lymphoblastic leukemia predicts response to SMO and GLI1 inhibitors. PMID: 27694322 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 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 Data indicate that agedunin induces its anti-metastatic effect through inhibition of sonic hedgehog protein [SHH] signaling. PMID: 26988754 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 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.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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