Cbl-b is an E3 ligase which regulates a large number of different signaling molecules in the cell. The mammalian Cbl family of proteins is highly conserved throughout evolution from nematodes to humans and consists of c-Cbl, Cbl-b, and Cbl-3. All three members of the Cbl family of proteins share a highly Homologous tyrosine kinase-binding (TKB) domain. The TKB domain is followed by a highly conserved helical linker (L) domain and a RING (really interesting new gene) finger (RF) domain, which bind to ubiquitin-conjugating enzymes (E2). In contrast, the C-terminal regions of this family of proteins are less conserved. Cbl-b has been demonstrated to play a crucial role in establishing the threshold for T-cell activation and controlling peripheral T-cell tolerance via multiple mechanisms.(1-3)

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