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CBL

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, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]
Full Name
Cbl Proto-Oncogene
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 (PubMed:17094949).
Ubiquitinates SPRY2 (PubMed:17094949, PubMed:17974561).
Ubiquitinates EGFR (PubMed:17974561).
Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC 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. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity).
Biological Process
Cell surface receptor signaling pathway Source: HGNC-UCL
Cellular response to DNA damage stimulus Source: Ensembl
Cellular response to epidermal growth factor stimulus Source: Ensembl
Cellular response to nerve growth factor stimulus Source: Ensembl
Cellular response to oxygen-glucose deprivation Source: Ensembl
Cellular response to platelet-derived growth factor stimulus Source: Ensembl
Cytokine-mediated signaling pathway Source: Reactome
Entry of bacterium into host cell Source: Reactome
Epidermal growth factor receptor signaling pathway Source: HGNC-UCL
Fibroblast growth factor receptor signaling pathway Source: Reactome
Interleukin-6-mediated signaling pathway Source: Reactome
Male gonad development Source: Ensembl
Mast cell degranulation Source: Ensembl
Membrane organization Source: Reactome
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of epidermal growth factor-activated receptor activity Source: GO_Central
Negative regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
Negative regulation of neuron death Source: Ensembl
Neuron death Source: Ensembl
Positive regulation of epidermal growth factor receptor signaling pathway Source: Reactome
Positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
Positive regulation of receptor-mediated endocytosis Source: UniProtKB
Protein monoubiquitination Source: Ensembl
Protein polyubiquitination Source: Ensembl
Protein ubiquitination Source: UniProtKB
Regulation of platelet-derived growth factor receptor-alpha signaling pathway Source: UniProtKB
Regulation of Rap protein signal transduction Source: Ensembl
Response to activity Source: Ensembl
Response to antibiotic Source: Ensembl
Response to ethanol Source: Ensembl
Response to gamma radiation Source: Ensembl
Response to starvation Source: Ensembl
Response to testosterone Source: Ensembl
Signal transduction Source: GO_Central
Transforming growth factor beta receptor signaling pathway Source: Reactome
Ubiquitin-dependent protein catabolic process Source: UniProtKB
Cellular Location
Cell membrane; Golgi apparatus; Cytoplasm; Cilium. Colocalizes with FGFR2 in lipid rafts at the cell membrane.
Involvement in disease
Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL): 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. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia.
PTM
Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and ZAP70 (By similarity). Phosphorylated on tyrosine residues in response to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR and FGR. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Not phosphorylated at Tyr-731 by FGFR3. Phosphorylated on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. Phosphorylated on tyrosine residues by HCK.
Ubiquitinated, leading to its degradation via the proteasome (PubMed:11896602, PubMed:20094046). Ubiquitination is negatively regulated by IFT20 (PubMed:29237719).

Anti-CBL antibodies

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Target: CBL
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human
Clone: 1G11
Application*: E, M
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBXC-0092
Application*: WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBXC-2511
Application*: DB, IC, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: CBXC-0091
Application*: IC, IP, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human
Clone: CBXC-3000
Application*: E, IP, WB
Target: CBL
Host: Human
Antibody Isotype: IgG1
Specificity: Human, Mouse
Clone: CBXC-0824
Application*: F
Target: CBL
Host: Human
Antibody Isotype: IgG1
Specificity: Human
Clone: CBXC-0713
Application*: F
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBFYC-0887
Application*: DB, IC, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Chicken, Dog, Mouse, Rat
Clone: CBFYC-0886
Application*: WB, IF, IH, IP
Target: CBL
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: CBFYC-0885
Application*: E, IF, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBFYC-0884
Application*: IC, IP, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse, Rat
Clone: CBFYC-0883
Application*: E, F, IH, WB
Target: CBL
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey
Clone: D4E10
Application*: WB, IP
Target: CBL
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human
Clone: S.551.7
Application*: IP, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse
Clone: 47/c-Cbl
Application*: FC
Target: CBL
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: 11D16
Application*: WB
Target: CBL
Host: Mouse
Specificity: Human
Clone: CBYY-C1025
Application*: WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Mouse
Clone: CBYY-C0503
Application*: WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse
Clone: CBYY-C0244
Application*: IS, WB, IF
Target: CBL
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: CBLC-LY-003
Application*: IC, IP, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: 8C50
Application*: WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Mouse
Clone: 648005
Application*: WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Mouse, Rat, Human
Clone: 3B12
Application*: WB, E, P, F, IC/IF
Target: CBL
Host: Mouse
Antibody Isotype: IgG3
Specificity: Human, Mouse, Pig, Rat
Clone: 2D3A2
Application*: E, WB, IH, IF
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 2111C3a
Application*: DB, C, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Mouse, Rat
Clone: 13B86
Application*: E, F, C, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: 0.T.12
Application*: IC, IP, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: 1762CT401.80.60
Application*: E, WB
Target: CBL
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human, Chicken, Dog, Mouse, Rat
Clone: 17/c-Cbl
Application*: WB, IF, IH, IP
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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