Anti-E3 ubiquitin-protein ligase CBL-C Antibody, clone 10F4.2 clone 10F4.2, from mouse

E3 ubiquitin-protein ligase CBL-C (UniProt Q9ULV8; also known as RING finger protein 57, SH3-binding protein CBL-3, SH3-binding protein CBL-C, Signal transduction protein CBL-C) is encoded by the CBLC (also known as CBL3, RNF57) gene (Gene ID 23624) in human. CBLC belongs to the CBL family of E3 ubiquitin ligases, members of which also include CBL (a.k.a. c-CBL) and CBL-B. Similar to CBL and CBL-B, CBL-C binds SH3 (Src homology 3) domain-containing proto-oncogenic tyrosine kinases such as EGFR, Lyn, Crk, Src and Ret. CBL-C is recruited to EGFR upon EGF stimulation, leading to CBL-C phosphorylation by EGFR and subsequent downstream MAP kinase signalling. In addition to mediating oncoprotein Ret ubiquitination for proteasomal degradation, CBL-C is shown to form a complex with HIC5 (Hydrogen peroxide-inducible clone 5) and the heat shock protein HSP27 that are necessary for the ubiquitination of NOX4. Unlike the other CBL family members, CBL-C expression appears to be restricted to epithelial tissues. Transgenic expression of CBL-C in mouse mammary gland causes impairment of cell proliferation, suggesting that CBL-C might have a growth-inhibitory role. CBL-C contains an N-terminal Cbl-type phosphotyrosine-binding (Cbl-PTB) domain (a.a. 7-321) that mediates SH3 domain interaction and a C-terminal RET-interacting region (a.a. 351-474) harboring the catalytic ring finger domain (a.a. 351-390) that mediates interaction with E2 ubiquitin-conjugating enzyme. The PTB domain, also known as tyrosine kinase-binding (TKB) domain, is subdivided into a four-helix bundle or 4H domain (a.a. 7-145), a calcium-binding EF hand-like domain (a.a. 146-218), and a SH2-like domain (a.a. 219-321).