This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Mar 2012]
Function:
Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. 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 KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. 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.
Subunit:
Interacts (phosphorylated at Tyr-731) with PIK3R1. Associates with NCK via its SH3 domain.
Subcellular Location:
Cytoplasm. Cell membrane. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane.
DISEASE:
Defects in CBL are the cause of Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:613563]. 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.
Similarity:
Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.
Contains 1 RING-type zinc finger.
Contains 1 UBA domain.
SWISS:
P22681
Gene ID:
867
Database links:
Entrez Gene: 867 Human
Entrez Gene: 1482 Mouse
Entrez Gene: 500985 Rat
Omim: 16572 Human
SwissProt: P22681 Human
SwissProt: P22682 Mouse
Unigene: 504096 Human
Unigene: 266871 Mouse
C CBL是泛素一蛋白酶体(ubiquitin proteasome)通路中的一个新的RINGFinger型泛素连接酶(ubiquitinligase ,E3).C CBL可以介导受体酪氨酸激酶和非受体酪氨酸受体激酶的降解.
|
|
