======= CBL =======
== Gene Information ==
* **Official Symbol**: CBL
* **Official Name**: Cbl proto-oncogene
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=867|867]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P22681|P22681]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=CBL&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CBL|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/165360|Open OMIM]]
== Function Summary ==
* **Entrez 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].
* **UniProt Summary**: 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, 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. {ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, ECO:0000269|PubMed:21596750}.
|Cbl N3|
|Cbl N2|
|zf-C3HC4|
|Cbl N|
|regulation of Rap protein signal transduction|
|regulation of platelet-derived growth factor receptor-alpha signaling pathway|
|entry of bacterium into host cell|
|response to oxygen-glucose deprivation|
|cellular response to oxygen-glucose deprivation|
|flotillin complex|
|phosphatidylinositol 3-kinase regulatory subunit binding|
|negative regulation of epidermal growth factor-activated receptor activity|
|interleukin-6-mediated signaling pathway|
|mast cell degranulation|
|mast cell activation involved in immune response|
|mast cell mediated immunity|
|cellular response to platelet-derived growth factor stimulus|
|response to platelet-derived growth factor|
|mast cell granule|
|mast cell activation|
|regulation of platelet-derived growth factor receptor signaling pathway|
|regulation of epidermal growth factor-activated receptor activity|
|ephrin receptor binding|
|negative regulation of protein tyrosine kinase activity|
|positive regulation of epidermal growth factor receptor signaling pathway|
|cellular response to interleukin-6|
|epidermal growth factor receptor binding|
|positive regulation of ERBB signaling pathway|
|response to interleukin-6|
|response to testosterone|
|phosphotyrosine residue binding|
|cellular response to epidermal growth factor stimulus|
|lysosome localization|
|negative regulation of epidermal growth factor receptor signaling pathway|
|response to epidermal growth factor|
|cellular response to nerve growth factor stimulus|
|epidermal growth factor receptor signaling pathway|
|negative regulation of peptidyl-tyrosine phosphorylation|
|negative regulation of ERBB signaling pathway|
|neuron death|
|response to nerve growth factor|
|positive regulation of receptor-mediated endocytosis|
|response to gamma radiation|
|receptor tyrosine kinase binding|
|negative regulation of signaling receptor activity|
|protein monoubiquitination|
|response to activity|
|ERBB signaling pathway|
|fibroblast growth factor receptor signaling pathway|
|regulation of epidermal growth factor receptor signaling pathway|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|regulation of protein tyrosine kinase activity|
|regulation of ERBB signaling pathway|
|positive regulation of endocytosis|
|regulation of receptor-mediated endocytosis|
|entry into host|
|entry into host cell|
|transforming growth factor beta receptor signaling pathway|
|cellular response to fibroblast growth factor stimulus|
|response to fibroblast growth factor|
|regulation of phosphatidylinositol 3-kinase signaling|
|response to ethanol|
|growth cone|
|SH3 domain binding|
|male gonad development|
|development of primary male sexual characteristics|
|response to ionizing radiation|
|cellular response to transforming growth factor beta stimulus|
|male sex differentiation|
|interaction with host|
|response to transforming growth factor beta|
|regulation of signaling receptor activity|
|response to starvation|
|response to ketone|
|cellular response to decreased oxygen levels|
|cilium|
|transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of endocytosis|
|negative regulation of neuron death|
|gonad development|
|cellular response to oxygen levels|
|development of primary sexual characteristics|
|ubiquitin protein ligase activity|
|negative regulation of protein kinase activity|
|membrane raft|
|response to alcohol|
|cellular response to nutrient levels|
|regulation of Ras protein signal transduction|
|negative regulation of kinase activity|
|ubiquitin-protein transferase activity|
|regulation of peptidyl-tyrosine phosphorylation|
|cellular response to extracellular stimulus|
|sex differentiation|
|negative regulation of transferase activity|
|protein polyubiquitination|
|response to antibiotic|
|cadherin binding|
|regulation of neuron death|
|cellular response to external stimulus|
|regulation of small GTPase mediated signal transduction|
|response to decreased oxygen levels|
|establishment of organelle localization|
|response to oxygen levels|
|negative regulation of protein phosphorylation|
|focal adhesion|
|reproductive structure development|
|reproductive system development|
|response to radiation|
|negative regulation of phosphorylation|
|response to nutrient levels|
|cellular response to growth factor stimulus|
|response to toxic substance|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|myeloid cell activation involved in immune response|
|ubiquitin-dependent protein catabolic process|
|response to extracellular stimulus|
|response to growth factor|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|regulation of vesicle-mediated transport|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|organelle localization|
|myeloid leukocyte activation|
|proteolysis involved in cellular protein catabolic process|
|negative regulation of protein modification process|
|cellular protein catabolic process|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|developmental process involved in reproduction|
|cytokine-mediated signaling pathway|
|protein catabolic process|
|protein ubiquitination|
|perinuclear region of cytoplasm|
|regulated exocytosis|
|enzyme linked receptor protein signaling pathway|
|calcium ion binding|
|leukocyte mediated immunity|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|symbiotic process|
|negative regulation of catalytic activity|
|exocytosis|
|regulation of protein kinase activity|
|interspecies interaction between organisms|
|membrane organization|
|response to lipid|
|regulation of kinase activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|cellular macromolecule catabolic process|
|response to hormone|
|response to organic cyclic compound|
|leukocyte activation|
|regulation of transferase activity|
|Golgi apparatus|
|protein modification by small protein conjugation or removal|
|positive regulation of transport|
|negative regulation of cell death|
|secretion by cell|
|cellular response to cytokine stimulus|
|positive regulation of intracellular signal transduction|
|response to drug|
|negative regulation of cellular protein metabolic process|
|export from cell|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|cell activation|
|cell death|
|immune effector process|
|response to cytokine|
|negative regulation of protein metabolic process|
|secretion|
|negative regulation of molecular function|
|response to abiotic stimulus|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|negative regulation of signal transduction|
|proteolysis|
|negative regulation of cell communication|
|negative regulation of signaling|
|reproductive process|
|reproduction|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|intracellular transport|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|negative regulation of response to stimulus|
|positive regulation of signal transduction|
|regulation of cell death|
|cellular response to stress|
|organic substance catabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|establishment of localization in cell|
|regulation of protein modification process|
|regulation of transport|
|immune response|
|vesicle-mediated transport|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp246|UM0011500 10μM R05 exp246]]|-2.1|
|[[:results:exp237|NN-Diethyl-meta-toluamide 100μM R05 exp237]]|-2.08|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|-1.92|
|[[:results:exp439|QNZ 0.01μM R08 exp439]]|-1.78|
|[[:results:exp226|Cerivastatin 0.15μM R05 exp226]]|-1.77|
|[[:results:exp415|Trichostatin-A 0.06μM R07 exp415]]|-1.76|
|[[:results:exp374|Latrunculin-B 10μM R07 exp374]]|1.75|
|[[:results:exp79|Q15 2.7μM R02 exp79]]|1.81|
|[[:results:exp346|CoCl2 18μM R07 exp346]]|1.88|
|[[:results:exp518|RK-33 8μM R08 exp518]]|1.91|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 10889
* **Expression level (log2 read counts)**: 6.48
{{:chemogenomics:nalm6 dist.png?nolink |}}