The mammalian cbl family of ubiquitin ligases consists of three homologs known as cbl (also known as c-Cbl), Cbl-B, and Cbl-3 which share highly conserved a tyrosine-kinase-binding domain, linker and RING finger domain in their amino-terminal halves. Similar to other E3 ubiquitin ligases, Cbl catalyzes the transfer of ubiquitin from an E2 or Ubc (ubiquitin-conjugating) enzyme to the e-amino group of a lysine residue of the substrate protein. Cbl acts to negatively regulate many types of cell-surface receptors, including the Syk protein tyrosine kinase family. Cbl is thought to be involved in T- and B-cell signaling, in addition to thymus development. Of the three known homologs in the cbl family, cbl antibody reacts specifically with cbl. Multiple isoforms of cbl have been reported.