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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| Cbl proto-oncogene | MIM:165360 | Ensembl:ENSG00000110395 | HGNC:HGNC:1541 | PA26115 | 11q23.3 |
GO terms in CBL
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IEA | GO:0001784 | phosphotyrosine residue binding |
| MF | TAS | GO:0003700 | DNA-binding transcription factor activity |
| MF | TAS | GO:0004842 | ubiquitin-protein transferase activity |
| MF | IEA | GO:0005154 | epidermal growth factor receptor binding |
| MF | IEA | GO:0005509 | calcium ion binding |
| MF | IPI | GO:0005515 | protein binding |
| MF | IBA | GO:0017124 | SH3 domain binding |
| MF | IPI | GO:0017124 | SH3 domain binding |
| MF | IBA | GO:0030971 | receptor tyrosine kinase binding |
| MF | IEA | GO:0036312 | phosphatidylinositol 3-kinase regulatory subunit binding |
| MF | HDA | GO:0045296 | cadherin binding |
| MF | IPI | GO:0046875 | ephrin receptor binding |
| MF | IBA | GO:0061630 | ubiquitin protein ligase activity |
| MF | TAS | GO:0061630 | ubiquitin protein ligase activity |
| BP | IEA | GO:0000209 | protein polyubiquitination |
| BP | IEA | GO:0006355 | regulation of transcription, DNA-templated |
| BP | IMP | GO:0006511 | ubiquitin-dependent protein catabolic process |
| BP | IEA | GO:0006513 | protein monoubiquitination |
| BP | IEA | GO:0006974 | cellular response to DNA damage stimulus |
| BP | IBA | GO:0007165 | signal transduction |
| BP | TAS | GO:0007166 | cell surface receptor signaling pathway |
| BP | TAS | GO:0007173 | epidermal growth factor receptor signaling pathway |
| BP | IBA | GO:0007175 | negative regulation of epidermal growth factor-activated receptor activity |
| BP | TAS | GO:0007179 | transforming growth factor beta receptor signaling pathway |
| BP | TAS | GO:0008543 | fibroblast growth factor receptor signaling pathway |
| BP | IEA | GO:0008584 | male gonad development |
| BP | IEA | GO:0010332 | response to gamma radiation |
| BP | IMP | GO:0014068 | positive regulation of phosphatidylinositol 3-kinase signaling |
| BP | IEA | GO:0014823 | response to activity |
| BP | TAS | GO:0016567 | protein ubiquitination |
| BP | TAS | GO:0019221 | cytokine-mediated signaling pathway |
| BP | IEA | GO:0033574 | response to testosterone |
| BP | TAS | GO:0035635 | entry of bacterium into host cell |
| BP | IEA | GO:0036120 | cellular response to platelet-derived growth factor stimulus |
| BP | IMP | GO:0042059 | negative regulation of epidermal growth factor receptor signaling pathway |
| BP | TAS | GO:0042059 | negative regulation of epidermal growth factor receptor signaling pathway |
| BP | IEA | GO:0042594 | response to starvation |
| BP | IMP | GO:0043066 | negative regulation of apoptotic process |
| BP | IEA | GO:0043303 | mast cell degranulation |
| BP | IEA | GO:0045471 | response to ethanol |
| BP | TAS | GO:0045742 | positive regulation of epidermal growth factor receptor signaling pathway |
| BP | IMP | GO:0048260 | positive regulation of receptor-mediated endocytosis |
| BP | TAS | GO:0048260 | positive regulation of receptor-mediated endocytosis |
| BP | TAS | GO:0061024 | membrane organization |
| BP | TAS | GO:0070102 | interleukin-6-mediated signaling pathway |
| BP | IEA | GO:0070997 | neuron death |
| BP | IEA | GO:0071364 | cellular response to epidermal growth factor stimulus |
| BP | IEA | GO:0090650 | cellular response to oxygen-glucose deprivation |
| BP | IEA | GO:1901215 | negative regulation of neuron death |
| BP | IEA | GO:1990090 | cellular response to nerve growth factor stimulus |
| CC | IDA | GO:0005829 | cytosol |
| CC | TAS | GO:0005829 | cytosol |
| CC | IBA | GO:0005886 | plasma membrane |
| CC | IDA | GO:0005886 | plasma membrane |
| CC | TAS | GO:0005886 | plasma membrane |
| CC | IEA | GO:0005925 | focal adhesion |
| CC | ISS | GO:0016600 | flotillin complex |
| CC | IEA | GO:0030426 | growth cone |
| CC | IEA | GO:0042629 | mast cell granule |
| CC | IBA | GO:0045121 | membrane raft |
| CC | IEA | GO:0048471 | perinuclear region of cytoplasm |
Gene expression in normal tissue: CBL
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in CBL
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| wikipathways | WP2018 | RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway |
| wikipathways | WP2037 | Prolactin Signaling Pathway |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| wikipathways | WP23 | B Cell Receptor Signaling Pathway |
| wikipathways | WP2512 | Integrated Lung Cancer Pathway |
| wikipathways | WP2593 | JAK-STAT |
| wikipathways | WP286 | IL-3 Signaling Pathway |
| wikipathways | WP304 | Kit receptor signaling pathway |
| wikipathways | WP3680 | Association Between Physico-Chemical Features and Toxicity Associated Pathways |
| wikipathways | WP3863 | T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection |
| wikipathways | WP3888 | VEGFA-VEGFR2 Signaling Pathway |
| wikipathways | WP3915 | Angiopoietin Like Protein 8 Regulatory Pathway |
| wikipathways | WP395 | IL-4 Signaling Pathway |
| wikipathways | WP4205 | MET in type 1 papillary renal cell carcinoma |
| wikipathways | WP437 | EGF-EGFR Signaling Pathway |
| wikipathways | WP481 | Insulin Signaling |
| wikipathways | WP49 | IL-2 Signaling Pathway |
| wikipathways | WP585 | Interferon type I signaling pathways |
| wikipathways | WP69 | T-Cell antigen Receptor (TCR) Signaling Pathway |
| kegg | hsa04012 | ErbB signaling pathway - Homo sapiens (human) |
| kegg | hsa04120 | Ubiquitin mediated proteolysis - Homo sapiens (human) |
| kegg | hsa04144 | Endocytosis - Homo sapiens (human) |
| kegg | hsa04910 | Insulin signaling pathway - Homo sapiens (human) |
| kegg | hsa05100 | Bacterial invasion of epithelial cells - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05205 | Proteoglycans in cancer - Homo sapiens (human) |
| kegg | hsa05220 | Chronic myeloid leukemia - Homo sapiens (human) |
| pid | avb3_integrin_pathway | Integrins in angiogenesis |
| pid | cd8tcrpathway | TCR signaling in naïve CD8+ T cells |
| pid | cdc42_pathway | CDC42 signaling events |
| pid | epha_fwdpathway | EPHA forward signaling |
| pid | epopathway | EPO signaling pathway |
| pid | erbb1_internalization_pathway | Internalization of ErbB1 |
| pid | fcer1pathway | Fc-epsilon receptor I signaling in mast cells |
| pid | fgf_pathway | FGF signaling pathway |
| pid | ifngpathway | IFN-gamma pathway |
| pid | il4_2pathway | IL4-mediated signaling events |
| pid | il8cxcr1_pathway | IL8- and CXCR1-mediated signaling events |
| pid | il8cxcr2_pathway | IL8- and CXCR2-mediated signaling events |
| pid | insulin_pathway | Insulin Pathway |
| pid | kitpathway | Signaling events mediated by Stem cell factor receptor (c-Kit) |
| pid | met_pathway | Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) |
| pid | pdgfrbpathway | PDGFR-beta signaling pathway |
| pid | tcr_pathway | TCR signaling in naïve CD4+ T cells |
| pid | vegfr1_2_pathway | Signaling events mediated by VEGFR1 and VEGFR2 |
| pid | vegfr1_pathway | VEGFR1 specific signals |
| netpath | Pathway_BCR | BCR |
| netpath | Pathway_EGFR1 | EGFR1 |
| netpath | Pathway_IL2 | IL2 |
| netpath | Pathway_IL3 | IL3 |
| netpath | Pathway_IL4 | IL4 |
| netpath | Pathway_IL5 | IL5 |
| netpath | Pathway_IL6 | IL6 |
| netpath | Pathway_KitReceptor | KitReceptor |
| netpath | Pathway_TCR | TCR |
| biocarta | cblpathway | cbl mediated ligand-induced downregulation of egf receptors pathway |
| biocarta | il2rbpathway | il-2 receptor beta chain in t cell activation |
| biocarta | sprypathway | sprouty regulation of tyrosine kinase signals |
| reactome | R-HSA-1059683 | Interleukin-6 signaling |
| reactome | R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants |
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-1280218 | Adaptive Immune System |
| reactome | R-HSA-1295596 | Spry regulation of FGF signaling |
| reactome | R-HSA-1433557 | Signaling by SCF-KIT |
| reactome | R-HSA-1433559 | Regulation of KIT signaling |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-1643713 | Signaling by EGFR in Cancer |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-170834 | Signaling by TGF-beta Receptor Complex |
| reactome | R-HSA-177929 | Signaling by EGFR |
| reactome | R-HSA-182971 | EGFR downregulation |
| reactome | R-HSA-190236 | Signaling by FGFR |
| reactome | R-HSA-199991 | Membrane Trafficking |
| reactome | R-HSA-2173789 | TGF-beta receptor signaling activates SMADs |
| reactome | R-HSA-449147 | Signaling by Interleukins |
| reactome | R-HSA-449147 | Signaling by Interleukins |
| reactome | R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling |
| reactome | R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling |
| reactome | R-HSA-5637810 | Constitutive Signaling by EGFRvIII |
| reactome | R-HSA-5637812 | Signaling by EGFRvIII in Cancer |
| reactome | R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer |
| reactome | R-HSA-5653656 | Vesicle-mediated transport |
| reactome | R-HSA-5654726 | Negative regulation of FGFR1 signaling |
| reactome | R-HSA-5654727 | Negative regulation of FGFR2 signaling |
| reactome | R-HSA-5654732 | Negative regulation of FGFR3 signaling |
| reactome | R-HSA-5654733 | Negative regulation of FGFR4 signaling |
| reactome | R-HSA-5654736 | Signaling by FGFR1 |
| reactome | R-HSA-5654738 | Signaling by FGFR2 |
| reactome | R-HSA-5654741 | Signaling by FGFR3 |
| reactome | R-HSA-5654743 | Signaling by FGFR4 |
| reactome | R-HSA-5663202 | Diseases of signal transduction |
| reactome | R-HSA-5663205 | Infectious disease |
| reactome | R-HSA-5663205 | Infectious disease |
| reactome | R-HSA-6783589 | Interleukin-6 family signaling |
| reactome | R-HSA-6806834 | Signaling by MET |
| reactome | R-HSA-6807004 | Negative regulation of MET activity |
| reactome | R-HSA-8848021 | Signaling by PTK6 |
| reactome | R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 |
| reactome | R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis |
| reactome | R-HSA-8856828 | Clathrin-mediated endocytosis |
| reactome | R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell |
| reactome | R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell |
| reactome | R-HSA-8876384 | Listeria monocytogenes entry into host cells |
| reactome | R-HSA-8876384 | Listeria monocytogenes entry into host cells |
| reactome | R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases |
| reactome | R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases |
| reactome | R-HSA-9006936 | Signaling by TGF-beta family members |
| reactome | R-HSA-912631 | Regulation of signaling by CBL |
| reactome | R-HSA-912631 | Regulation of signaling by CBL |
| reactome | R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messengers |
| reactome | R-HSA-983705 | Signaling by the B Cell Receptor (BCR) |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD202 | Curcumin | 3 |
| iGMDRD103 | SN-38 | 3 |
| iGMDRD5 | Tyrphostin AG 1478 | 6 |
| iGMDRD192 | CIL56 | 3 |
| iGMDRD289 | Parthenolide | 3 |
| iGMDRD481 | Dactolisib | 1 |
| iGMDRD269 | Purmorphamine | 2 |
| iGMDRD662 | JQ-1 | 3 |
| iGMDRD147 | Prima-1 | 4 |
| iGMDRD246 | NPC26 | 4 |
| iGMDRD932 | JAK inhibitor | 4 |
| iGMDRD307 | Manumycin A | 1 |
| iGMDRD148 | Pifithrin-mu | 1 |
| iGMDRD512 | nutlin 3 | 4 |
| iGMDRD424 | Tamatinib | 4 |
| iGMDRD701 | NVP-AUY922 | 7 |
| iGMDRD85 | Ursolic acid | 4 |
| iGMDRD57 | Chloropentafluorobenzene | 6 |
| iGMDRD123 | Isoevodiamine | 3 |
| iGMDRD211 | (1S,3R)-RSL3 | 3 |
| iGMDRD511 | CHEMBL399379 | 3 |
| iGMDRD945 | ML214 | 3 |
| iGMDRD138 | PX 12 | 3 |
| iGMDRD513 | BML-259 | 1 |
| iGMDRD171 | Pemetrexed | 3 |
| iGMDRD887 | Compound 23 citrate | 3 |
| iGMDRD398 | Sepantronium | 4 |
| iGMDRD562 | Navitoclax | 3 |
| iGMDRD690 | PRIMA-1MET | 4 |
| iGMDRD451 | Serdemetan | 4 |
| iGMDRD444 | Tivantinib | 1 |
| iGMDRD126 | Tipifarnib | 1 |
| iGMDRD76 | Simvastatin | 1 |
| iGMDRD599 | Salermide | 3 |
| iGMDRD889 | Compound 7d-cis | 1 |
| iGMDRD239 | Dasatinib | 4 |
| iGMDRD427 | ABT737 | 4 |
| iGMDRD670 | ML 210 | 3 |
| iGMDRD394 | BX-795 | 2 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in CBL
CLASSFICATION
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