C-Cbl (C-Terminal Region) (CBL) Antibody – Mouse Monoclonal

The cbl oncogene was first identified as part of a transforming retrovirus which induces mouse pre-B and pro-B cell lymphomas. As an adaptor protein for receptor protein-tyrosine kinases, it positively regulates receptor protein-tyrosine kinase ubiquitination in a manner dependent upon its variant SH2 and RING finger domains. Ubiquitination of receptor protein-tyrosine kinases terminates signaling by marking active receptors for degradation. [provided by RefSeq]

Function: Participates in signal transduction in hematopoietic cells. Adapter protein that functions as a negative regulator of many signaling pathways that start from receptors at the cell surface. 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. Recognizes activated receptor tyrosine kinases, including PDGFA, EGF and CSF1, and terminates signaling. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Ref.4 Ref.17

Pathway: Protein modification; protein ubiquitination.

Subunit structure: Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2. May interact with CBLB

By similarity. Ref.6 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16

Subcellular location: Cytoplasm.

Domain: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.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.

Post-translational modification: Phosphorylated on tyrosine residues by EGFR, SYK, FYN and ZAP70

By similarity. Phosphorylated on tyrosine residues by INSR. Ref.5 Ref.7 Ref.9 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24

Involvement in disease: Defects in CBL are the cause of Noonan syndrome-like disorder (NSL) [

MIM:613563]. NSL is a syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Ref.29

Miscellaneous: This protein has one functional calcium-binding site.

Sequence similarities: Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.Contains 1 RING-type zinc finger.Contains 1 UBA domain.