Recombinant Human E3 ubiquitin-protein ligase CBL(CBL) ,partial

Code CSB-YP004578HU
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Source Yeast
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Code CSB-EP004578HU
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Source E.coli
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Code CSB-EP004578HU-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP004578HU
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Source Baculovirus
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Code CSB-MP004578HU
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Source Mammalian cell
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Product Details

Purity >85% (SDS-PAGE)
Target Names CBL
Uniprot No. P22681
Alternative Names 4732447J05Rik; C CBL; Cas Br M (murine) ecotropic retroviral transforming sequence; Casitas B lineage lymphoma proto oncogene; Casitas B-lineage lymphoma proto-oncogene; CBL 2; cbl; CBL_HUMAN; CBL2; E3 ubiquitin protein ligase CBL; E3 ubiquitin-protein ligase CBL; Oncogene CBL2; Proto oncogene c CBL; Proto-oncogene c-CBL; RGD1561386; RING finger protein 55; RNF55; Signal transduction protein CBL
Species Homo sapiens (Human)
Protein Length Partial
Tag Info The following tags are available.
N-terminal His-tagged
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer before Lyophilization Tris/PBS-based buffer, 6% Trehalose, pH 8.0
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
and FAQs
Protein FAQs
Storage Condition Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet Please contact us to get it.

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Target Background

Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Ubiquitinates SPRY2. Ubiquitinates EGFR. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA.
Gene References into Functions
  1. Authors observed that delta-catenin plays a key role in EGFR stability and downstream signaling. delta-Catenin competes with c-Cbl for EGFR binding, which results in a reduction of binding between c-Cbl and EGFR and thus decreases the ubiquitination of EGFR. PMID: 29629558
  2. its mutation is genetic predictor of tumor reduction in glucocorticoid-treated patients with chronic myelomonocytic leukemia. PMID: 29600428
  3. c-CBL might play a role in the pathogenesis of inflammatory dermatoses and cutaneous T-cell lymphoma PMID: 27805921
  4. Two germline de novo mutations in CBL were identified in patients with infancy-onset severe Moyamoya angiopathy who also presented subtle signs of RASopathy. PMID: 28343148
  5. Patients harbouring ASXL1 and/or CBL mutations (n = 8, 8 deaths, median OS = 11 months) had a significantly worse OS as compared to those without either mutation (n = 11, 4 deaths, median OS = 84 months) (P = 0.0002) (Fig 1a). PMID: 26628266
  6. the loss of c-Cbl activity significantly enhanced nuclear beta-catenin and colorectal cancer tumor growth in cell culture and a mouse xenograft model. PMID: 27661103
  7. we have shown that c-CBL plays a supportive role in the proliferation, migration and invasion of human melanoma cells. PMID: 27472394
  8. Findings show for this first time that ATG9A loss in trastuzumab resistant cells allowed Her2 to escape from lysosomal targeted degradation through K63 poly-ubiquitination via c-Cbl. PMID: 27050377
  9. c-Cbl negatively regulates IFN-beta signaling and cellular antiviral response by promoting IRF3 ubiquitination and degradation. PMID: 27503123
  10. These results suggest MET overexpression is related to altered c-CBL expression in head and neck squamous cell carcinoma, which may influence tumorigenesis PMID: 27244893
  11. This study identified a new regulatory axis in which miR-124-3p and CBL regulate the proliferation and invasion of breast cancer cells. PMID: 27842510
  12. The viral entry receptor Nectin-1 is also internalized during HSV-1 infection in a Cbl-dependent mechanism, and that increases the opportunity of the virus to spread to uninfected cells. PMID: 28381567
  13. mutant CBL proteins effectively compete with the remaining wild type CBL-B and juxtapose tyrosine kinase-binding domain-associated protein tyrosine kinases with proline-rich region-associated signaling proteins to hyper-activate signaling downstream of hematopoietic growth factor receptors PMID: 28082680
  14. we report that two JMML patients survived >20 years without HSCT and both patients had uniparental disomy of 11q23 where CBL is located without the phenomenon found in neither Noonan syndrome nor Noonan syndrome-like disorder. We think that some JMML patients with CBL mutation might show the good prognosis in later life after remission of JMML. PMID: 26911351
  15. we found that CQ decreased the expression of Cbl, an E3 ligase of DR5, and knock-down of Cbl markedly enhanced DR5 up-regulation. Other lysosomal inhibitors, including monensin and nigericin, also up-regulated DR5 and sensitized TRAIL-mediated apoptosis PMID: 26964637
  16. miR-513a-5p, miR-22-3p and miR-625-5p may have an impact on the regulation of the immune response and inflammatory cytokine pathways through the regulation of their target gene(s), CBL, PPARGC1B and ESR1, which may then lead to a dust mite-induced asthma attack PMID: 27277384
  17. Data suggest that the combination of peritumoral Cbl and EGFR serves as a much stronger indicator to make an accurate prognosis, especially during early recurrence. PMID: 26474280
  18. H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b. PMID: 26353930
  19. By up-regulating the expression of c-Cbl and Cbl-b, which leads to inhibition of PI3K/Akt signaling and down-regulation of P-gp expression, beta-elemene is capable of enhancing the efficacy of doxorubicin in leukemia and gastric cancer cells. PMID: 23665906
  20. Genotype-phenotype correlation analysis performed on available records indicated that germline CBL mutations cause a variable phenotype characterized by a relatively high frequency of neurological features, predisposition to diseases. PMID: 25952305
  21. The result indicated that TMZ may overcome TRAIL resistance in GSCs by suppressing c-FLIP expression through c-Cbl-mediated ubiquitination and degradation PMID: 26142735
  22. Overexpression of Smad7 in human HaCaT keratinocyte cells and mouse skin tissues elevated EGF receptor (EGFR) activity by impairing ligand-induced ubiquitination and degradation of activated receptor, which is induced by the E3 ubiquitin ligase c-Cbl. PMID: 26055326
  23. Here we report on three unrelated patients with CBL mutations manifesting with hydrops fetalis, fetal pleural effusions and/or congenital hydro-/chylothorax. Our findings further connect the CBL syndrome with the RASopathies. PMID: 25358541
  24. These results suggest that dysregulation of ubiquitination is a key mechanism of EGFR hyperactivation in PDAC and that low CBL may define PDAC tumors likely to respond to erlotinib treatment. PMID: 25348515
  25. The penetrance of the CBL Y371C mutation was 30% for JMML and 40% for all leukemia. PMID: 25939664
  26. novel mechanism for the regulation of active nuclear beta-catenin by c-Cbl and its critical role in angiogenesis. PMID: 25784557
  27. Erbin promotes tumourigenesis and tumour growth in colorectal cancer by stabilizing epidermal growth factor receptor PMID: 25521828
  28. RASopathy-associated CBL germline mutations cause aberrant ubiquitylation and trafficking of EGFR. PMID: 25178484
  29. Cbl negatively regulates EPO signaling mainly through the proteasome-dependent degradation of Src, and the E3 ligase activity of Cbl and its tyrosine phosphorylation are regulated by Src but not Jak2. PMID: 25084697
  30. c-CBL E3 ubiquitin ligase is upregulated in cutaneous T-cell lymphoma. PMID: 25140833
  31. molecular or pharmacologic inhibition of the Lyn-PI3K/AKT pathway, markedly increased the sensitivity of the otherwise chemoresistant Cbl mutant-JMML cells to chemotherapeutic agents currently used in the treatment of JMML patients PMID: 24469048
  32. Germline mutation of CBL is associated with moyamoya disease in a child with juvenile myelomonocytic leukemia and Noonan syndrome-like disorder. PMID: 25283271
  33. over time with physiological levels of receptor phosphorylation, cell surface receptors produced either enhanced or sustained mitogen-activated protein kinase kinase (MEK), Casitas B-lineage lymphoma (c-Cbl), and the pro-oncogene Src activity PMID: 25074934
  34. c-Cbl negatively regulates alphaPix-mediated cell migration and invasion; the lack of c-Cbl in C6 and A172 glioma cells is responsible for their malignant behavior PMID: 25450678
  35. We demonstrate for the first time a significant decrease in c-Cbl mRNA levels in the prefrontal cortex of suicide subjects indicating the possible role of c-Cbl in the pathophysiology of suicidal behavior. PMID: 24845182
  36. Data indicate that suppression of c-Cbl protein by rho guanine nucleotide exchange factor 7 (Cool-1) may be critical for generation of at least a subset of glioblastoma (GBM). PMID: 24458840
  37. Copy neutral loss of heterozygosity for the CBL mutation. PMID: 24458550
  38. Our findings suggest that c-Cbl deregulation is a recurrent event that could be playing a role in the acquisition of invasiveness properties of colorectal cancer cells PMID: 24525700
  39. c-Cbl regulates MICA- but not ULBP2-induced NKG2D down-modulation in human NK cells. PMID: 24846123
  40. Mechanistic model of EGFR endocytosis to determine the relative contributions of three parallel pathways of MIG6, ubiquitin ligase CBL and Sprouty2. PMID: 24445374
  41. Low cbl-c expression is associated with breast neoplasms. PMID: 24466333
  42. The data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relatively infrequent in oral squamous cell carcinoma samples. PMID: 23621189
  43. A PKC-SHP1 signaling axis desensitizes Fcgamma receptor signaling by reducing the tyrosine phosphorylation of CBL and regulates FcgammaR mediated phagocytosis. PMID: 24886428
  44. The results suggest that proteins, post-translational modifications or mutations that alter structural flexibility of the TKB domain of Cbl-family proteins could regulate their binding to target phosphoproteins and thereby, affect PTK-mediated signalling. PMID: 22888118
  45. c-Cbl activation promotes myocyte apoptosis, inhibits angiogenesis, and causes adverse cardiac remodeling after myocardial infarction. PMID: 24583314
  46. LOH of the mutated CBL allele can be absent in children with bona fide JMML and CBL mutations PMID: 23823657
  47. Data suggest that EPHA2 (ephrin type-A receptor 2) regulates polyubiquitination via proto-oncogene protein c-CBL, phosphorylation of clathrin, integrin signal transduction, and endocytosis of Kaposi sarcoma-associated herpesvirus into fibroblasts. PMID: 23874206
  48. CBL(mut) are frequent in chronic myelomonocytic leukemia. PMID: 22733026
  49. The expression of Cbl-b gene in MM patients (median: 0.714%) also dropped significantly. PMID: 23948411
  50. This study also showed that ubiquitin ligase proteins Cbl-b and c-Cbl might be involved in IL-2-induced Jurkat T-cell activation by negatively regulating the MAPK/ERK signaling pathway. PMID: 23586039

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Involvement in disease Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)
Subcellular Location Cytoplasm. Cell membrane. Cell projection, cilium. Golgi apparatus. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane.
Database Links

HGNC: 1541

OMIM: 165360

KEGG: hsa:867

STRING: 9606.ENSP00000264033

UniGene: Hs.504096

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