CBL


Summary: 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].

NameOMIM IDEnsembl IDHGNC IDPHARMGKB IDMap Location
Cbl proto-oncogeneMIM:165360Ensembl:ENSG00000110395HGNC:HGNC:1541PA2611511q23.3

GO terms in CBL


Term TypeEvidence TypeGO Term IDGO Des.
MFIEAGO:0001784phosphotyrosine residue binding
MFTASGO:0003700DNA-binding transcription factor activity
MFTASGO:0004842ubiquitin-protein transferase activity
MFIEAGO:0005154epidermal growth factor receptor binding
MFIEAGO:0005509calcium ion binding
MFIPIGO:0005515protein binding
MFIBAGO:0017124SH3 domain binding
MFIPIGO:0017124SH3 domain binding
MFIBAGO:0030971receptor tyrosine kinase binding
MFIEAGO:0036312phosphatidylinositol 3-kinase regulatory subunit binding
MFHDAGO:0045296cadherin binding
MFIPIGO:0046875ephrin receptor binding
MFIBAGO:0061630ubiquitin protein ligase activity
MFTASGO:0061630ubiquitin protein ligase activity
BPIEAGO:0000209protein polyubiquitination
BPIEAGO:0006355regulation of transcription, DNA-templated
BPIMPGO:0006511ubiquitin-dependent protein catabolic process
BPIEAGO:0006513protein monoubiquitination
BPIEAGO:0006974cellular response to DNA damage stimulus
BPIBAGO:0007165signal transduction
BPTASGO:0007166cell surface receptor signaling pathway
BPTASGO:0007173epidermal growth factor receptor signaling pathway
BPIBAGO:0007175negative regulation of epidermal growth factor-activated receptor activity
BPTASGO:0007179transforming growth factor beta receptor signaling pathway
BPTASGO:0008543fibroblast growth factor receptor signaling pathway
BPIEAGO:0008584male gonad development
BPIEAGO:0010332response to gamma radiation
BPIMPGO:0014068positive regulation of phosphatidylinositol 3-kinase signaling
BPIEAGO:0014823response to activity
BPTASGO:0016567protein ubiquitination
BPTASGO:0019221cytokine-mediated signaling pathway
BPIEAGO:0033574response to testosterone
BPTASGO:0035635entry of bacterium into host cell
BPIEAGO:0036120cellular response to platelet-derived growth factor stimulus
BPIMPGO:0042059negative regulation of epidermal growth factor receptor signaling pathway
BPTASGO:0042059negative regulation of epidermal growth factor receptor signaling pathway
BPIEAGO:0042594response to starvation
BPIMPGO:0043066negative regulation of apoptotic process
BPIEAGO:0043303mast cell degranulation
BPIEAGO:0045471response to ethanol
BPTASGO:0045742positive regulation of epidermal growth factor receptor signaling pathway
BPIMPGO:0048260positive regulation of receptor-mediated endocytosis
BPTASGO:0048260positive regulation of receptor-mediated endocytosis
BPTASGO:0061024membrane organization
BPTASGO:0070102interleukin-6-mediated signaling pathway
BPIEAGO:0070997neuron death
BPIEAGO:0071364cellular response to epidermal growth factor stimulus
BPIEAGO:0090650cellular response to oxygen-glucose deprivation
BPIEAGO:1901215negative regulation of neuron death
BPIEAGO:1990090cellular response to nerve growth factor stimulus
CCIDAGO:0005829cytosol
CCTASGO:0005829cytosol
CCIBAGO:0005886plasma membrane
CCIDAGO:0005886plasma membrane
CCTASGO:0005886plasma membrane
CCIEAGO:0005925focal adhesion
CCISSGO:0016600flotillin complex
CCIEAGO:0030426growth cone
CCIEAGO:0042629mast cell granule
CCIBAGO:0045121membrane raft
CCIEAGO:0048471perinuclear region of cytoplasm

Gene expression in normal tissue: CBL

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in CBL


DatabasePathway IDPathway Des.
wikipathwaysWP2018RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway
wikipathwaysWP2037Prolactin Signaling Pathway
wikipathwaysWP2261Signaling Pathways in Glioblastoma
wikipathwaysWP23B Cell Receptor Signaling Pathway
wikipathwaysWP2512Integrated Lung Cancer Pathway
wikipathwaysWP2593JAK-STAT
wikipathwaysWP286IL-3 Signaling Pathway
wikipathwaysWP304Kit receptor signaling pathway
wikipathwaysWP3680Association Between Physico-Chemical Features and Toxicity Associated Pathways
wikipathwaysWP3863T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection
wikipathwaysWP3888VEGFA-VEGFR2 Signaling Pathway
wikipathwaysWP3915Angiopoietin Like Protein 8 Regulatory Pathway
wikipathwaysWP395IL-4 Signaling Pathway
wikipathwaysWP4205MET in type 1 papillary renal cell carcinoma
wikipathwaysWP437EGF-EGFR Signaling Pathway
wikipathwaysWP481Insulin Signaling
wikipathwaysWP49IL-2 Signaling Pathway
wikipathwaysWP585Interferon type I signaling pathways
wikipathwaysWP69T-Cell antigen Receptor (TCR) Signaling Pathway
kegghsa04012ErbB signaling pathway - Homo sapiens (human)
kegghsa04120Ubiquitin mediated proteolysis - Homo sapiens (human)
kegghsa04144Endocytosis - Homo sapiens (human)
kegghsa04910Insulin signaling pathway - Homo sapiens (human)
kegghsa05100Bacterial invasion of epithelial cells - Homo sapiens (human)
kegghsa05200Pathways in cancer - Homo sapiens (human)
kegghsa05205Proteoglycans in cancer - Homo sapiens (human)
kegghsa05220Chronic myeloid leukemia - Homo sapiens (human)
pidavb3_integrin_pathwayIntegrins in angiogenesis
pidcd8tcrpathwayTCR signaling in naïve CD8+ T cells
pidcdc42_pathwayCDC42 signaling events
pidepha_fwdpathwayEPHA forward signaling
pidepopathwayEPO signaling pathway
piderbb1_internalization_pathwayInternalization of ErbB1
pidfcer1pathwayFc-epsilon receptor I signaling in mast cells
pidfgf_pathwayFGF signaling pathway
pidifngpathwayIFN-gamma pathway
pidil4_2pathwayIL4-mediated signaling events
pidil8cxcr1_pathwayIL8- and CXCR1-mediated signaling events
pidil8cxcr2_pathwayIL8- and CXCR2-mediated signaling events
pidinsulin_pathwayInsulin Pathway
pidkitpathwaySignaling events mediated by Stem cell factor receptor (c-Kit)
pidmet_pathwaySignaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
pidpdgfrbpathwayPDGFR-beta signaling pathway
pidtcr_pathwayTCR signaling in naïve CD4+ T cells
pidvegfr1_2_pathwaySignaling events mediated by VEGFR1 and VEGFR2
pidvegfr1_pathwayVEGFR1 specific signals
netpathPathway_BCRBCR
netpathPathway_EGFR1EGFR1
netpathPathway_IL2IL2
netpathPathway_IL3IL3
netpathPathway_IL4IL4
netpathPathway_IL5IL5
netpathPathway_IL6IL6
netpathPathway_KitReceptorKitReceptor
netpathPathway_TCRTCR
biocartacblpathwaycbl mediated ligand-induced downregulation of egf receptors pathway
biocartail2rbpathwayil-2 receptor beta chain in t cell activation
biocartasprypathwaysprouty regulation of tyrosine kinase signals
reactomeR-HSA-1059683Interleukin-6 signaling
reactomeR-HSA-1236382Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
reactomeR-HSA-1280215Cytokine Signaling in Immune system
reactomeR-HSA-1280215Cytokine Signaling in Immune system
reactomeR-HSA-1280218Adaptive Immune System
reactomeR-HSA-1295596Spry regulation of FGF signaling
reactomeR-HSA-1433557Signaling by SCF-KIT
reactomeR-HSA-1433559Regulation of KIT signaling
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-1643685Disease
reactomeR-HSA-1643685Disease
reactomeR-HSA-1643713Signaling by EGFR in Cancer
reactomeR-HSA-168256Immune System
reactomeR-HSA-168256Immune System
reactomeR-HSA-170834Signaling by TGF-beta Receptor Complex
reactomeR-HSA-177929Signaling by EGFR
reactomeR-HSA-182971EGFR downregulation
reactomeR-HSA-190236Signaling by FGFR
reactomeR-HSA-199991Membrane Trafficking
reactomeR-HSA-2173789TGF-beta receptor signaling activates SMADs
reactomeR-HSA-449147Signaling by Interleukins
reactomeR-HSA-449147Signaling by Interleukins
reactomeR-HSA-512988Interleukin-3, Interleukin-5 and GM-CSF signaling
reactomeR-HSA-512988Interleukin-3, Interleukin-5 and GM-CSF signaling
reactomeR-HSA-5637810Constitutive Signaling by EGFRvIII
reactomeR-HSA-5637812Signaling by EGFRvIII in Cancer
reactomeR-HSA-5637815Signaling by Ligand-Responsive EGFR Variants in Cancer
reactomeR-HSA-5653656Vesicle-mediated transport
reactomeR-HSA-5654726Negative regulation of FGFR1 signaling
reactomeR-HSA-5654727Negative regulation of FGFR2 signaling
reactomeR-HSA-5654732Negative regulation of FGFR3 signaling
reactomeR-HSA-5654733Negative regulation of FGFR4 signaling
reactomeR-HSA-5654736Signaling by FGFR1
reactomeR-HSA-5654738Signaling by FGFR2
reactomeR-HSA-5654741Signaling by FGFR3
reactomeR-HSA-5654743Signaling by FGFR4
reactomeR-HSA-5663202Diseases of signal transduction
reactomeR-HSA-5663205Infectious disease
reactomeR-HSA-5663205Infectious disease
reactomeR-HSA-6783589Interleukin-6 family signaling
reactomeR-HSA-6806834Signaling by MET
reactomeR-HSA-6807004Negative regulation of MET activity
reactomeR-HSA-8848021Signaling by PTK6
reactomeR-HSA-8849469PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1
reactomeR-HSA-8856825Cargo recognition for clathrin-mediated endocytosis
reactomeR-HSA-8856828Clathrin-mediated endocytosis
reactomeR-HSA-8875360InlB-mediated entry of Listeria monocytogenes into host cell
reactomeR-HSA-8875360InlB-mediated entry of Listeria monocytogenes into host cell
reactomeR-HSA-8876384Listeria monocytogenes entry into host cells
reactomeR-HSA-8876384Listeria monocytogenes entry into host cells
reactomeR-HSA-9006927Signaling by Non-Receptor Tyrosine Kinases
reactomeR-HSA-9006934Signaling by Receptor Tyrosine Kinases
reactomeR-HSA-9006936Signaling by TGF-beta family members
reactomeR-HSA-912631Regulation of signaling by CBL
reactomeR-HSA-912631Regulation of signaling by CBL
reactomeR-HSA-983695Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
reactomeR-HSA-983705Signaling by the B Cell Receptor (BCR)

Gene-Drug: Aster Plot


Drug IDDrug NameModel Num.
iGMDRD202Curcumin3
iGMDRD103SN-383
iGMDRD5Tyrphostin AG 14786
iGMDRD192CIL563
iGMDRD289Parthenolide3
iGMDRD481Dactolisib1
iGMDRD269Purmorphamine2
iGMDRD662JQ-13
iGMDRD147Prima-14
iGMDRD246NPC264
iGMDRD932JAK inhibitor4
iGMDRD307Manumycin A1
iGMDRD148Pifithrin-mu1
iGMDRD512nutlin 34
iGMDRD424Tamatinib4
iGMDRD701NVP-AUY9227
iGMDRD85Ursolic acid4
iGMDRD57Chloropentafluorobenzene6
iGMDRD123Isoevodiamine3
iGMDRD211(1S,3R)-RSL33
iGMDRD511CHEMBL3993793
iGMDRD945ML2143
iGMDRD138PX 123
iGMDRD513BML-2591
iGMDRD171Pemetrexed3
iGMDRD887Compound 23 citrate3
iGMDRD398Sepantronium4
iGMDRD562Navitoclax3
iGMDRD690PRIMA-1MET4
iGMDRD451Serdemetan4
iGMDRD444Tivantinib1
iGMDRD126Tipifarnib1
iGMDRD76Simvastatin1
iGMDRD599Salermide3
iGMDRD889Compound 7d-cis1
iGMDRD239Dasatinib4
iGMDRD427ABT7374
iGMDRD670ML 2103
iGMDRD394BX-7952

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in CBL

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