10.5 kb; 2718 bp open reading frame

906 amino acids; 115 kDa; the evolutionarily conserved amino-terminal region of CBL is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium binding domain, and a divergent SH2 domain; the three domains together form an integrated phosphoprotein-recognition module; this aminoterminal region is followed by a central Ring finger with a Cys3HisCys4 motif and a carboxy-terminal region with multiple proline-rich sequences, a putative leucine zipper and several potential tyrosine phosphorylation sites

ubiquitous but predominant in hematopoietic cells

cytoplasmic; cellular activation induces translocation of CBL to the plasma membrane or cytoskeleton

CBL has been shown to have a negative regulatory activity in protein tyrosine kinase-mediated signaling pathways; CBL overexpresion inhibits cell growth resulting from activation of the EGF and PDGF receptors (EGFR, PDGFRa, PDFFRb) and enhances ubiquitination and degradation of these receptors; CBL also negatively regulates the tyrosine phosphorylation of ZAP70 substrates in T cells

the fragile site FRA11B has been localized to a stretch of CCG trinucleotides found in the 5 part of the CBL gene and has been involved in the pathogenesis of a proportion of inherited Jacobsen syndroms (OMIM 147791) which have a del(11)(q23qter) telomeric of an expansion of the stretch of CCG tripletsSOMATIC in 9% of the genetically unstable sporadic gastrointestinal tumors, an extension of an ATG trinucleotide repeat with no translation shift was detected in the coding region of CBL; this alteration was not present in cancers without the mutator phenotype