Recombinant Human alk5 Protein (aa 200-503, His & GST Tag)

Beta LifeScience SKU/CAT #: BLPSN-0146

Recombinant Human alk5 Protein (aa 200-503, His & GST Tag)

Beta LifeScience SKU/CAT #: BLPSN-0146
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Product Overview

Tag His&GST
Host Species Human
Accession P36897
Synonym AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1, LDS1A, LDS2A, MSSE, SKR4, tbetaR-I, TGFR-1
Background Transforming growth factor, beta receptor I, also known as Transforming growth factor-beta receptor type I , Serine / threonine-protein kinase receptor R4, Activin receptor-like kinase 5, SKR4, ALK-5, and TGFBR1, is a single-pass type I membrane protein which belongs to the protein kinase superfamily and TGFB receptor subfamily. TGFBR1 / ALK-5 is found in all tissues examined. It is most abundant in placenta and least abundant in brain and heart. TGF-beta functions as a tumor suppressor by inhibiting the cell cycle in the G1 phase. Administration of TGF-beta is able to protect against mammary tumor development in transgenic mouse models in vivo. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers, with the majority of colon and gastric cancers being caused by an inactivating mutation of TGF-beta RII. On ligand binding, TGFBR1 / ALK-5 forms a receptor complex consisting of two type I I and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which auto-phosphorylate, then bind and activate SMAD transcriptional regulators. TGF-beta signaling via TGFBR1 / ALK-5 is not required in myocardial cells during mammalian cardiac development, but plays an irreplaceable cell-autonomous role regulating cellular communication, differentiation and proliferation in endocardial and epicardial cells. Defects in TGFBR1 / ALK-5 are the cause of Loeys-Dietz syndrome type 1A (LDS1A), Loeys-Dietz syndrome type 2A (LDS2A), and aortic aneurysm familial thoracic type 5 (AAT5).
Description A DNA sequence encoding the human ALK5 (P36897-1) (Thr200-Mey503) was fused with the N-terminal His-tagged GST tag at the N-terminus.
Source Baculovirus-Insect Cells
Predicted N Terminal Met
AA Sequence Thr200-Mey503
Molecular Weight The recombinant human ALK5/GST chimera consists of 541 a.a. and has a calculated molecular mass of 62.6 kDa. The recombinant protein migrates approximately 57 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 The specific activity was determined to be > 10 nmol/min/mg using casein as substrate.
Formulation Supplied as sterile 20mM Tris, 500mM Nacl, pH 8.5, 10% glycerol.
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 Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.
Subcellular Location Cell membrane; Single-pass type I membrane protein. Cell junction, tight junction. Cell surface. Membrane raft.
Protein Families Protein kinase superfamily, TKL Ser/Thr protein kinase family, TGFB receptor subfamily
Database References
Associated Diseases Loeys-Dietz syndrome 1 (LDS1); Multiple self-healing squamous epithelioma (MSSE)
Tissue Specificity Found in all tissues examined, most abundant in placenta and least abundant in brain and heart. Expressed in a variety of cancer cell lines.

Gene Functions References

  1. GPR50 is a TbetaRI co-receptor with potential impact on cancer development PMID: 29572483
  2. Systemic activation of Activin A signaling causes chronic kidney disease-mineral bone disorder. (Review) PMID: 30142896
  3. TGFbetaR1 rs10739778 was associated with blood pressure in healthy pregnant women. PMID: 29183791
  4. Treatment of T. cruzi-infected cardiac spheroids with SB 431542, a selective inhibitor of TGF-b type I receptor, resulted in a reduction in the size of spheroids, which was accompanied by a decrease in parasite load and in fibronectin expression. PMID: 29208458
  5. TGFBR1/2 genetic variants (in particular when evaluated as a burden by score) might play a role in modulating the severity of cardiovascular manifestation in Marfan syndrome. PMID: 28847661
  6. Findings provide evidence that TGFBR-1 expression is regulated by SLC35F2 which exerts its oncogenic effect on papillary thyroid carcinoma progression through activation of TGFBR-1 and ASK-1. PMID: 29274137
  7. rs334348 polymorphism may influence individual's susceptibility to endometriosis and its severity PMID: 28277133
  8. miR-130a-3p might play a critical role in negatively regulating hepatic stellate cell activation and proliferation in the progression of nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2 via the TGF-beta/SMAD signaling pathway. PMID: 28518142
  9. TGFbetaR1 signaling was involved in 14-3-3zeta-mediated cell proliferation and metastasis of lung squamous cell carcinoma cells. PMID: 27764818
  10. Mutational activation of BRAF confers sensitivity to TGFBR1 inhibitors in human melanoma cells. PMID: 27835901
  11. Loeys-Dietz syndrome patients with confirmed mutations in TGFBR1 or TGFBR2 had an increased prevalence of inflammatory bowel disease PMID: 27508510
  12. ALK5 is an important mediator of HTFs fibrosis. ALK5 is a potential therapeutic target to suppress scar formation after filtration surgery. PMID: 28632033
  13. PAR2 is crucial for TGF-beta1-induced cell motility by its ability to sustain expression of ALK5. Therapeutically targeting PAR2 may thus be a promising approach in preventing TGF-beta-dependent driven metastatic dissemination in PDAC and possibly other stroma-rich tumour types. PMID: 27248167
  14. Data show that twist-related protein 1 (Twist1) requires TGF-beta type-I receptor (TGFBR1)-activation for activation for epithelial-mesenchymal transition (EMT)-induction. PMID: 27105506
  15. combined inhibition of ALK5 and CTGF is required to prevent TGFbeta-induced nodule formation in tri-cellular cultures PMID: 28815607
  16. Aortic diseases in patients with TGFBR1 or TGFBR2 mutations show the same prevalence of systemic features and the same global survival. PMID: 27879313
  17. In this small cohort, the results did not reach significance to identify the TFGBR1*6A allele as a major modifier for aortic dilation, ectopia lentis, or systemic features associated with MFS or other connective tissue disorders. PMID: 27112580
  18. Results show that TGFBR1 expression is regulated in bladder cancer cell through its desumoylation by SENP2. PMID: 28574613
  19. Low TGFBR1 expression is associated with oral cancer progression. PMID: 28146434
  20. TGF-beta type I, II, and III receptors were all identified in pregnant serum; all were substantially elevated in early-onset but not late-onset preeclampsia. Endoglin was increased in both subtypes. PMID: 28633389
  21. Overexpression of truncated ALK5 in a B-cell line counteracted BMP-7-induced apoptosis, whereas overexpression of truncated ALK4 had no effect. PMID: 28489883
  22. Although TGFbeta1/2 receptors are downregulated in breast cancer, their expression in tumors is an indicator of aggressive breast cancer phenotype. PMID: 27445263
  23. Higher proportions of early-onset Diffuse Gastric Cancers (DGCs) contained somatic mutations in CDH1 or TGFBR1 compared with late-onset DGCs. A smaller proportion of early-onset DGCs contained somatic mutations in RHOA. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times. Female predominance in early-onset DGC may be related to relatively high rates of somatic CDH1 and TGFBR1 mutations. PMID: 28522256
  24. Coronin 1B constitutively binds to TGF beta receptor I in vascular smooth muscle cells. PMID: 28625921
  25. BIX02189 is a potent inhibitor of TGF-beta type I receptor that can block the lung tumor metastatic activity of TGF-beta1. PMID: 27543359
  26. In luciferase assays, the risk-associated allele for rs868 was associated with half the luciferase expression in the presence of miRNA let-7b-5p compared with protective allele, suggesting more binding of let-7b-5p and less TGFBR1 expression. Thus, rs868 potentially is acolorectal ca CRC risk-causing allele. Our results support the concept that rs868 is associated with lower TGFBR1 expression thereby increasing CRC risk. PMID: 27234654
  27. Data show that signal transducing adaptor proteins APPL1 and APPL2 are required for TGFbeta-induced nuclear translocation of TGFbeta type I receptor (TbetaRI)-ICD and for cancer cell invasiveness of prostate and breast cancer cell lines. PMID: 26583432
  28. Evidence supporting a genetic basis includes the autosomal dominance of Bicuspid aortic valve inheritance patterns, and the identification of mutations in transforming growth factor beta receptor 1. PMID: 26766164
  29. This work details a novel mechanism by which cellular tension regulates TGFbeta receptor organization, multimerization, and function. PMID: 26652004
  30. miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFbetaR1/Smad signaling pathway. PMID: 26620926
  31. Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes and transforming growth factor beta receptor 1 PMID: 26548632
  32. Studies indicate that the transforming growth factor beta receptor I 6A (TbetaR-I 6A) allele was associated with breast cancer risk. PMID: 26616150
  33. Women who carry the TGFBR1*6A allele are at lower risk of developing breast cancer. PMID: 26165686
  34. Data suggest that transient suppression of TGFbeta receptor I (TGFbeta receptor) signaling may improve the outcome of islet transplantation. PMID: 26872091
  35. Blocking TGFBR1 receptor up-regulated p21 expression while inhibiting breast tumor cell growth. PMID: 26187313
  36. Short hairpin-mediated downregulation of either ALK5 or ALK1 resulted in a strong inhibition of TGFbeta-induced chondrogenesis. PMID: 26720610
  37. MiR-1343 reduces the expression of both TGF-beta receptor 1 and 2 by directly targeting their 3'-UTRs. PMID: 26542979
  38. these findings demonstrate that syntenin may act as an important positive regulator of TGF-b signaling by regulating caveolin-1-mediated internalization of TbRI; thus, providing a novel function for syntenin that is linked to cancer progression PMID: 25893292
  39. Int7G24A polymorphism of gene TGFBR1 involved in the TGF-beta signaling pathway had a significantly increased risk for cancer development. (Meta-analysis) PMID: 26074400
  40. Data show that macitentan interferes with the profibrotic action of transforming growth factor-beta (TGF-beta), blocking the endothelin receptor type A (ET-1 receptor) portion of the ET-1/TGF-beta receptor complex. PMID: 26357964
  41. Treatment with a TGFBR1 kinase inhibitor, endocytosis inhibitors or a lysosome inhibitor, normalized the levels of TGFBR1 and TGFBR2. PMID: 25882708
  42. we showed significantly higher HDAC6 levels in GBM from the patients and further showed evidence supporting TGFbeta receptor signaling pathway as a downstream target of HDAC6 in glioblastoma multiforme PMID: 26150340
  43. results indicate the critical role of TGF-beta R1/Smad2/3 signaling in carbon nanotube-induced fibrogenesis by upregulating collagen production in lung fibroblasts PMID: 26472812
  44. The direct fusion of clathrin-coated and caveolae vesicles during TGF-beta receptor endocytic trafficking, which leads to the formation of the multifunctional sorting device, caveolin-1-positive early endosomes, for TGF-beta receptors. PMID: 25998683
  45. Data show that tacrolimus-induced NAD(P)H-oxidase 4 (Nox4) expression in by aberrant TGF-beta receptor signalling. PMID: 24816588
  46. a case-control study and systematic literature review found that sporadic, but not familial colorectal cancer, was associated with TGFBR1*6A polymorphism. PMID: 24880985
  47. Chinese Han family a pathogenic mutation (rs111426349, c.1459C >T) (TGFBR1) of familial thoracic aortic aneurysm was confirmed, which result in the amino acid substitution p.R487W. PMID: 25110237
  48. TGFBR1 mutations in patients with dural ectasia in Loeys-Dietz syndrome PMID: 24344637
  49. Donor rs868 AA genotype was associated with worse clinical course of recurrent hepatitis C and more severe symptoms of hepatitis C and fibrosis during follow-up after liver transplantation. PMID: 25502482
  50. Characteristic TGFbetaR1 expression pattern in keratoacanthoma can facilitate histopathologic distinction from squamous cell carcinoma. PMID: 24954139


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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.

To learn more about how to properly dissolve the lyophilized recombinant protein, please visit Lyophilization FAQs.

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