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Casitas B-lineage lymphoma proto-oncogene B (Cbl-b) is an E3 ubiquitin ligase and a member of Cbl RING-type E3 ubiquitin ligases.1,2 It is composed of an N-terminal tyrosine kinase-binding domain, a helix linker region, and a RING finger domain, which is necessary for Cbl-b homodimerization and heterodimerization with the related homolog c-Cbl, and a C-terminal region containing proline- and tyrosine-rich motifs and a ubiquitin-association domain.2 Cbl-b is autoinhibited by its helix linker region but folds into the active conformation following tyrosine 371 phosphorylation by various kinases.3 Cbl-b is ubiquitously expressed but primarily found in leukocytes and is found in the cytoplasm.1 It has roles in negatively regulating immune cell responses, preventing autoimmune activity, and promoting immune tolerance by targeting receptor and non-receptor tyrosine kinase signaling proteins for proteasomal degradation.1,4 Knockout of Cblb increases the percentage of natural killer (NK) cells expressing IFN-γ, as well as decreases tumor volume and number of total metastases, in a B16/F10 murine melanoma model of metastasis.4 Knockout of Cblb increases serum IgG levels, as well as induces Cd28-independent lymphocyte hyperproliferation and B and T cell infiltration into the pancreas, salivary glands, and lungs, in mice.5 Cbl-b levels are decreased in T cell lymphocytes isolated from patients with systemic lupus erythematosus (SLE).6 Cayman's Cbl-b Substrate-binding Domain (human, recombinant) protein has a calculated molecular weight of 48.2 kDa.
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1. Modulation of immune cell functions by the E3 ligase Cbl-
2. The co-
3. Casitas B-
4. The E3 ligase Cbl-
5. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-
6. Expression and function of Cbl-