Recombinant Human SHH Protein (C24II)

Name: Recombinant Human SHH Protein (C24II)
Brand: Beta LifeScience
SKU: BL-2024NP
Availability: InStock

BL-2024NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)

Collections: Cytokines, Other recombinant proteins, Recombinant proteins

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Product Overview

Description	Recombinant Human Sonic Hedgehog is produced by our E.coli expression system and the target gene encoding Cys24-Gly197 (C24II) is expressed.
Accession	Q15465
Synonym	Sonic Hedgehog Protein; SHH; HHG-1; SHH
Gene Background	Sonic Hedgehog Homolog (SHH) belongs to a three-protein family called Hedgehog. The other two family members are Indian Hedgehog (IHH) and Desert Hedgehog (DHH). Hedgehog proteins are key signaling molecules in embryonic development. SHH is expressed in various embryonic tissues and plays critical roles in regulating the patterning of many systems, such as limbs and brain. SHH also plays an important role in adult, including the division of adult stem cells and the development of certain cancers and other diseases. Human SHH is expressed as a 45kDa precursor, and undergoes a series of processing during secretion. After the removal of the signal peptide, a protease within the C-terminal domain catalyzes the cleavage of SHH into a 20 kDa N-terminal signaling domain (SHH-N) and a 25 kDa C-terminal domain (SHH-C). SHH-N has the “all signaling” capability. SHH-N binds to the 12 pass transmembrane protein Patched (Ptc) on cell surface, which releases the repression of the activity of Smoothened (Smo), a G-protein coupled receptor, by Ptc.
Molecular Mass	19.8 KDa
Apmol Mass	20 KDa, reducing conditions
Formulation	Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4.
Endotoxin	Less than 0.001 ng/µg (0.01 EU/µg) as determined by LAL test.
Purity	Greater than 95% as determined by reducing SDS-PAGE. (QC verified)
Biological Activity	Not tested
Reconstitution	Always centrifuge tubes before opening.Do not mix by vortex or pipetting.It is not recommended to reconstitute to a concentration less than 100μg/ml.Dissolve the lyophilized protein in distilled water.Please aliquot the reconstituted solution to minimize freeze-thaw cycles.
Storage	Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt.Reconstituted protein solution can be stored at 2-8°C for 2-7 days.Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months.
Shipping	The product is shipped at ambient temperature.Upon receipt, store it immediately at the temperature listed below.
Usage	For Research Use Only

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: Hs.164537
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

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
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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