CBLC
Domain
EF-hand-like and Sh2-like domains are required for N-terminal inhibition of E3 activity.
The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
Function
Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Functionally coupled with the E2 ubiquitin-protein ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-419'. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival.
Post-translational modifications
Phosphorylated on multiple tyrosine residues by SRC. Isoform 1, but not isoform 2, is phosphorylated on tyrosines by EGFR.
Autoubiquitinated when phosphorylated at Tyr-341, enhanced by SRC; suggesting proteasomal degradation.
Tissue Specificity
Ubiquitous.
Alternative names
CBL3, RNF57, CBLC, E3 ubiquitin-protein ligase CBL-C, RING finger protein 57, RING-type E3 ubiquitin transferase CBL-C, SH3-binding protein CBL-3, SH3-binding protein CBL-C, Signal transduction protein CBL-C