Cbl adaptor proteins are RING-type E3 ubiquitin ligases. Cbl may be involved in the negative regulation of thymocyte development, targeting its substrate for ubiquitination . The ubiquitin ligase activity of Cbl, and of its homologue Cbl-b, plays a role in the negative regulation of upstream kinases, such as Lck, Syk and PI3K, in T and B cells . Cbl can interact with the EGF receptor (EGFR), causing the ubiquitination of the receptor following EGF ligand binding and Grb2 association. Ubiquitination is required for ligand-induced endocytosis of the EGFR .
The N-terminal region is composed of three evolutionarily conserved domains: an N-terminal four-helix bundle domain, an EF Hand-like domain and a SH2-like domain, which together are known to bind to phosphorylated tyrosine residues. This entry represents the N-terminal four-helical bundle domain.