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CBL Cbl proto-oncogene [ Homo sapiens (human) ]

Gene ID: 867, updated on 16-Jul-2019

Summary

Official Symbol
CBLprovided by HGNC
Official Full Name
Cbl proto-oncogeneprovided by HGNC
Primary source
HGNC:HGNC:1541
See related
Ensembl:ENSG00000110395 MIM:165360
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CBL2; NSLL; C-CBL; RNF55; FRA11B
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]
Expression
Broad expression in testis (RPKM 12.3), lymph node (RPKM 6.0) and 23 other tissues See more
Orthologs

Genomic context

See CBL in Genome Data Viewer
Location:
11q23.3
Exon count:
16
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 11 NC_000011.10 (119206276..119308149)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (119076986..119178859)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 11099 Neighboring gene small nucleolar RNA, C/D box 150 Neighboring gene coiled-coil domain containing 153 Neighboring gene FRA11B repeat instability region Neighboring gene RNA, U6 small nuclear 262, pseudogene Neighboring gene melanoma cell adhesion molecule Neighboring gene microRNA 6756 Neighboring gene ring finger protein 26

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Juvenile myelomonocytic leukemia
MedGen: C0349639 OMIM: 607785 GeneReviews: Not available
Compare labs
Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
MedGen: C3150803 OMIM: 613563 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated (2019-04-24)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated (2019-04-24)

ClinGen Genome Curation Page

NHGRI GWAS Catalog

Description
New gene functions in megakaryopoiesis and platelet formation.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Nef nef In the presence of Nef, lipid raft Cdc42 is activated and forms a ternary complex between the c-Cbl-interacting protein p85Cool-1/betaPix and c-Cbl, displacing UbcH7 from rafts PubMed
nef HIV-1 Nef enhances the phosphorylation of c-Cbl in CD4+ T cells, an effect that requires the Src tyrosine kinase Lck PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Angiopoietin Like Protein 8 Regulatory Pathway, organism-specific biosystem (from WikiPathways)
    Angiopoietin Like Protein 8 Regulatory Pathway, organism-specific biosystemThe hepatic ANGPTL8 (Angiopoietin Like Protein 8) regulatory pathway represents an up-to-date curated interactive pathway for all of the interactions from the known regulators of ANGPTL8 and updated ...
  • Antigen activates B Cell Receptor (BCR) leading to generation of second messengers, organism-specific biosystem (from REACTOME)
    Antigen activates B Cell Receptor (BCR) leading to generation of second messengers, organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, Fu et al. 1975, Kunkel e...
  • Association Between Physico-Chemical Features and Toxicity Associated Pathways, organism-specific biosystem (from WikiPathways)
    Association Between Physico-Chemical Features and Toxicity Associated Pathways, organism-specific biosystemThis pathway is based on Figure 8 of "Mapping drug physico-chemical features to pathway activity reveals molecular networks linked to toxicity outcome."(See bibliography). These 3 pathways demonstr...
  • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
    B Cell Receptor Signaling Pathway, organism-specific biosystemThe functional B-cell receptor is a multi-protein complex consisting of an antigen binding subunit and a signaling subunit. The antigen binding subunit is the membrane bound immunoglobulin and the si...
  • Bacterial invasion of epithelial cells, organism-specific biosystem (from KEGG)
    Bacterial invasion of epithelial cells, organism-specific biosystemMany pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. Invasive bacteria induce their own uptake by non-ph...
  • Bacterial invasion of epithelial cells, conserved biosystem (from KEGG)
    Bacterial invasion of epithelial cells, conserved biosystemMany pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize them intracellularly, then become disseminated to other cells. Invasive bacteria induce their own uptake by non-ph...
  • CDC42 signaling events, organism-specific biosystem (from Pathway Interaction Database)
    CDC42 signaling events, organism-specific biosystem
    CDC42 signaling events
  • Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystemRecruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-...
  • Chronic myeloid leukemia, organism-specific biosystem (from KEGG)
    Chronic myeloid leukemia, organism-specific biosystemChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (C...
  • Chronic myeloid leukemia, conserved biosystem (from KEGG)
    Chronic myeloid leukemia, conserved biosystemChronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (C...
  • Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
  • Constitutive Signaling by EGFRvIII, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by EGFRvIII, organism-specific biosystemIn glioblastoma, the most prevalent EGFR mutation, present in ~25% of tumors, is the deletion of the ligand binding domain of EGFR, accompanied with amplification of the mutated allele, which results...
  • Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants, organism-specific biosystemSignaling by EGFR is frequently activated in cancer through activating mutations in the coding sequence of the EGFR gene, resulting in expression of a constitutively active mutant protein. Epidermal ...
  • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
    Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
    Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
  • EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
    EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
  • EGFR downregulation, organism-specific biosystem (from REACTOME)
    EGFR downregulation, organism-specific biosystemRegulation of receptor tyrosine kinase (RTK) activity is implicated in the control of almost all cellular functions. One of the best understood RTKs is epidermal growth factor receptor (EGFR). Growth...
  • EPHA forward signaling, organism-specific biosystem (from Pathway Interaction Database)
    EPHA forward signaling, organism-specific biosystem
    EPHA forward signaling
  • EPHA2 forward signaling, organism-specific biosystem (from Pathway Interaction Database)
    EPHA2 forward signaling, organism-specific biosystem
    EPHA2 forward signaling
  • EPO signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    EPO signaling pathway, organism-specific biosystem
    EPO signaling pathway
  • Endocytosis, organism-specific biosystem (from KEGG)
    Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endocytosis, conserved biosystem (from KEGG)
    Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • ErbB signaling pathway, organism-specific biosystem (from KEGG)
    ErbB signaling pathway, organism-specific biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
  • ErbB signaling pathway, conserved biosystem (from KEGG)
    ErbB signaling pathway, conserved biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
  • FGF signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    FGF signaling pathway, organism-specific biosystem
    FGF signaling pathway
  • Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem (from Pathway Interaction Database)
    Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem
    Fc-epsilon receptor I signaling in mast cells
  • IFN-gamma pathway, organism-specific biosystem (from Pathway Interaction Database)
    IFN-gamma pathway, organism-specific biosystem
    IFN-gamma pathway
  • IL-2 Signaling Pathway, organism-specific biosystem (from WikiPathways)
    IL-2 Signaling Pathway, organism-specific biosystemIL-2 is a multifunctional cytokine with pleiotropic effects on several cells of the immune system. IL-2 was originally discovered as a T cell growth factor, but it was also found to have actions rela...
  • IL-3 Signaling Pathway, organism-specific biosystem (from WikiPathways)
    IL-3 Signaling Pathway, organism-specific biosystemInterleukin 3 (IL-3) is a potent growth factor belonging to the super family of cytokines. IL-3 is a 20- 32kDa glycoprotein involved in the process of hematopoiesis. It is involved in the proliferati...
  • IL-4 Signaling Pathway, organism-specific biosystem (from WikiPathways)
    IL-4 Signaling Pathway, organism-specific biosystemIL-4 is a glycoprotein which is composed of 129 amino acids and has a molecular weight of 20kDa. IL-4 and IL-13 are produced by CD4+ cells and exhibit significant functional overlap. Both these cytok...
  • IL4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL4-mediated signaling events, organism-specific biosystem
    IL4-mediated signaling events
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • InlB-mediated entry of Listeria monocytogenes into host cell, organism-specific biosystem (from REACTOME)
    InlB-mediated entry of Listeria monocytogenes into host cell, organism-specific biosystemInlB, a cell wall protein of Listeria monocytogenes, binds MET receptor, acting as an HGF agonist (Shen et al. 2000, Veiga and Cossart 2005). Listeria monocytogenes InlB proteins dimerize through the...
  • Insulin Pathway, organism-specific biosystem (from Pathway Interaction Database)
    Insulin Pathway, organism-specific biosystem
    Insulin Pathway
  • Insulin Signaling, organism-specific biosystem (from WikiPathways)
    Insulin Signaling, organism-specific biosystemInsulin signaling influences energy metabolism as well as growth. The presence of insulin signals the fed state, and this signal is passed via the AKT branch, which leads to the uptake of glucose fro...
  • Insulin signaling pathway, organism-specific biosystem (from KEGG)
    Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
  • Insulin signaling pathway, conserved biosystem (from KEGG)
    Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
  • Integrins in angiogenesis, organism-specific biosystem (from Pathway Interaction Database)
    Integrins in angiogenesis, organism-specific biosystem
    Integrins in angiogenesis
  • Interferon type I signaling pathways, organism-specific biosystem (from WikiPathways)
    Interferon type I signaling pathways, organism-specific biosystemThe type I IFNs (IFN? family, IFN?, IFN?, IFN? and IFN?) all bind to and signal via the type I IFN receptor complex. The type I receptor consists of two main IFNAR1, IFNAR2c receptor chains and other...
  • Interleukin-3, 5 and GM-CSF signaling, organism-specific biosystem (from REACTOME)
    Interleukin-3, 5 and GM-CSF signaling, organism-specific biosystemThe Interleukin-3 (IL-3), IL-5 and Granulocyte-macrophage colony stimulating factor (GM-CSF) receptors form a family of heterodimeric receptors that have specific alpha chains but share a common beta...
  • Interleukin-6 family signaling, organism-specific biosystem (from REACTOME)
    Interleukin-6 family signaling, organism-specific biosystemThe interleukin (IL)-6 family of cytokines is defined by the shared use of the common signal transducing receptor gp130 beta-subunit. This family includes structurally and functionally related IL-6, ...
  • Interleukin-6 signaling, organism-specific biosystem (from REACTOME)
    Interleukin-6 signaling, organism-specific biosystemInterleukin-6 (IL-6) is a pleiotropic cytokine with roles in processes including immune regulation, hematopoiesis, inflammation, oncogenesis, metabolic control and sleep. It is the founding member o...
  • Internalization of ErbB1, organism-specific biosystem (from Pathway Interaction Database)
    Internalization of ErbB1, organism-specific biosystem
    Internalization of ErbB1
  • Kit receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Kit receptor signaling pathway, organism-specific biosystemKit is a cytokine receptor that belongs to the type III receptor tyrosine kinase family. It is structurally similar to platelet-derived growth factor recpetors (PDGFRs), colony stimulating factor-1 r...
  • Listeria monocytogenes entry into host cells, organism-specific biosystem (from REACTOME)
    Listeria monocytogenes entry into host cells, organism-specific biosystemListeria monocytogenes is a short, gram-positive, nonspore-forming motile rod. Serotypes 1/2a, 1/2b and 4b make up more than 95% of isolates from humans, with serotype 4b causing most of the food-bor...
  • Membrane Trafficking, organism-specific biosystem (from REACTOME)
    Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
  • Negative regulation of FGFR1 signaling, organism-specific biosystem (from REACTOME)
    Negative regulation of FGFR1 signaling, organism-specific biosystemOnce activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-m...
  • Negative regulation of FGFR2 signaling, organism-specific biosystem (from REACTOME)
    Negative regulation of FGFR2 signaling, organism-specific biosystemOnce activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-m...
  • Negative regulation of FGFR3 signaling, organism-specific biosystem (from REACTOME)
    Negative regulation of FGFR3 signaling, organism-specific biosystemOnce activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-m...
  • Negative regulation of FGFR4 signaling, organism-specific biosystem (from REACTOME)
    Negative regulation of FGFR4 signaling, organism-specific biosystemOnce activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-m...
  • Negative regulation of MET activity, organism-specific biosystem (from REACTOME)
    Negative regulation of MET activity, organism-specific biosystemSignaling by MET receptor is negatively regulated mainly by MET receptor dephosphorylation or MET receptor degradation. Protein tyrosine phosphatase PTPRJ dephosphorylates MET tyrosine residue Y1349,...
  • Notch signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Notch signaling pathway, organism-specific biosystem
    Notch signaling pathway
  • PDGFR-beta signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    PDGFR-beta signaling pathway, organism-specific biosystem
    PDGFR-beta signaling pathway
  • PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1, organism-specific biosystem (from REACTOME)
    PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1, organism-specific biosystemPTK6 enhances EGFR signaling by inhibiting EGFR down-regulation (Kang et al. 2010, Li et al. 2012, Kang and Lee 2013). PTK6 may also enhance signaling by other receptor tyrosine kinases (RTKs), such ...
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Paxillin-dependent events mediated by a4b1, organism-specific biosystem (from Pathway Interaction Database)
    Paxillin-dependent events mediated by a4b1, organism-specific biosystem
    Paxillin-dependent events mediated by a4b1
  • Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem (from Pathway Interaction Database)
    Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem
    Paxillin-independent events mediated by a4b1 and a4b7
  • Prolactin Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Prolactin Signaling Pathway, organism-specific biosystemProlactin (PRL), a pleiotropic polypeptide hormone, mostly secreted by the lactotrophic cells of anterior pituitary gland and to a lesser extent expressed in numerous extra pituitary tissues such as ...
  • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
    Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • Proteoglycans in cancer, conserved biosystem (from KEGG)
    Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
  • RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway, organism-specific biosystem (from WikiPathways)
    RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway, organism-specific biosystemRANKL (Receptor activator of nuclear factor-kappa B ligand), RANK (Receptor activator of nuclear factor-kappa B) and the natural decoy receptor of RANKL, OPG (Osteoprotegerin) are three important mol...
  • Reelin signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Reelin signaling pathway, organism-specific biosystem
    Reelin signaling pathway
  • Regulation of KIT signaling, organism-specific biosystem (from REACTOME)
    Regulation of KIT signaling, organism-specific biosystemSCF induced proliferation is negatively regulated by various proteins including SHP1, PKC, CBL, SOCS1, SOCS6 and LNK.
  • Regulation of signaling by CBL, organism-specific biosystem (from REACTOME)
    Regulation of signaling by CBL, organism-specific biosystemCbl is an E3 ubiquitin-protein ligase that negatively regulates signaling pathways by targeting proteins for ubiquitination and proteasomal degradation (Rao et al. 2002). Cbl negatively regulates PI3...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
    Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...
  • Signaling by EGFR, organism-specific biosystem (from REACTOME)
    Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
  • Signaling by EGFR in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by EGFR in Cancer, organism-specific biosystemThe pathway "Signaling by EGFR in Cancer" shows signaling by constitutively active EGFR cancer variants in the context of "Signaling by EGFR", allowing users to compare cancer events with the wild-ty...
  • Signaling by EGFRvIII in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by EGFRvIII in Cancer, organism-specific biosystemEGFRvIII (EGFR V30_R297delinsG) is the most prevalent EGFR variant in glioblastoma, but it is also found in other cancer types. In-frame deletion of the ligand binding domain in EGFRvIII is frequentl...
  • Signaling by FGFR, organism-specific biosystem (from REACTOME)
    Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
  • Signaling by FGFR1, organism-specific biosystem (from REACTOME)
    Signaling by FGFR1, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
  • Signaling by FGFR2, organism-specific biosystem (from REACTOME)
    Signaling by FGFR2, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
  • Signaling by FGFR3, organism-specific biosystem (from REACTOME)
    Signaling by FGFR3, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
  • Signaling by FGFR4, organism-specific biosystem (from REACTOME)
    Signaling by FGFR4, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
  • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
    Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
  • Signaling by Ligand-Responsive EGFR Variants in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by Ligand-Responsive EGFR Variants in Cancer, organism-specific biosystemLigand-responsive EGFR cancer variants harbor mutations in the kinase domain or point mutations in the extracellular domain. These altered EGFR proteins are able to signal in the absence of ligands, ...
  • Signaling by MET, organism-specific biosystem (from REACTOME)
    Signaling by MET, organism-specific biosystemMET is a receptor tyrosine kinase (RTK) (Cooper et al. 1984, Park et al. 1984) activated by binding to its ligand, Hepatocyte growth factor/Scatter factor (HGF/SF) (Bottaro et al. 1991, Naldini et al...
  • Signaling by PTK6, organism-specific biosystem (from REACTOME)
    Signaling by PTK6, organism-specific biosystemPTK6 (BRK) is an oncogenic non-receptor tyrosine kinase that functions downstream of ERBB2 (HER2) (Xiang et al. 2008, Peng et al. 2015) and other receptor tyrosine kinases, such as EGFR (Kamalati et ...
  • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
    Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
  • Signaling by TGF-beta Receptor Complex, organism-specific biosystem (from REACTOME)
    Signaling by TGF-beta Receptor Complex, organism-specific biosystemThe TGF-beta/BMP pathway incorporates several signaling pathways that share most, but not all, components of a central signal transduction engine. The general signaling scheme is rather simple: upon ...
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
    Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
  • Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem
    Signaling events mediated by Stem cell factor receptor (c-Kit)
  • Spry regulation of FGF signaling, organism-specific biosystem (from REACTOME)
    Spry regulation of FGF signaling, organism-specific biosystemSprouty was initially characterized as a negative regulator of FGFR signaling in Drosophila. Human cells contain four genes encoding Sprouty proteins, of which Spry2 is the best studied and most wid...
  • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
    T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • T cell receptor signaling pathway, conserved biosystem (from KEGG)
    T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystem (from WikiPathways)
    T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
  • T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystem (from WikiPathways)
    T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystemThis pathway is based on Figure 4 of "A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus au...
  • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
    TCR signaling in naive CD4+ T cells, organism-specific biosystem
    TCR signaling in naive CD4+ T cells
  • TCR signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
    TCR signaling in naive CD8+ T cells, organism-specific biosystem
    TCR signaling in naive CD8+ T cells
  • TGF-beta receptor signaling activates SMADs, organism-specific biosystem (from REACTOME)
    TGF-beta receptor signaling activates SMADs, organism-specific biosystemBinding of transforming growth factor beta 1 (TGF beta 1, i.e. TGFB1) to TGF beta receptor type 2 (TGFBR2) activates TGF beta receptor signaling cascade. TGFB1 is posttranslationally processed by fur...
  • Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
    Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
    Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
  • VEGFR1 specific signals, organism-specific biosystem (from Pathway Interaction Database)
    VEGFR1 specific signals, organism-specific biosystem
    VEGFR1 specific signals
  • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
    Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
SH3 domain binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SH3 domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
cadherin binding HDA PubMed 
calcium ion binding IEA
Inferred from Electronic Annotation
more info
 
ephrin receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
epidermal growth factor receptor binding IEA
Inferred from Electronic Annotation
more info
 
phosphatidylinositol 3-kinase regulatory subunit binding IEA
Inferred from Electronic Annotation
more info
 
phosphotyrosine residue binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor tyrosine kinase binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase activity TAS
Traceable Author Statement
more info
 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
cell surface receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
cellular response to DNA damage stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to epidermal growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to nerve growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to oxygen-glucose deprivation IEA
Inferred from Electronic Annotation
more info
 
cellular response to platelet-derived growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
entry of bacterium into host cell TAS
Traceable Author Statement
more info
 
epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
fibroblast growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
interleukin-6-mediated signaling pathway TAS
Traceable Author Statement
more info
 
male gonad development IEA
Inferred from Electronic Annotation
more info
 
mast cell degranulation IEA
Inferred from Electronic Annotation
more info
 
membrane organization TAS
Traceable Author Statement
more info
 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of epidermal growth factor receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
negative regulation of epidermal growth factor-activated receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of neuron death IEA
Inferred from Electronic Annotation
more info
 
neuron death IEA
Inferred from Electronic Annotation
more info
 
positive regulation of epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
positive regulation of phosphatidylinositol 3-kinase signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of receptor-mediated endocytosis IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of receptor-mediated endocytosis TAS
Traceable Author Statement
more info
PubMed 
protein monoubiquitination IEA
Inferred from Electronic Annotation
more info
 
protein polyubiquitination IEA
Inferred from Electronic Annotation
more info
 
protein ubiquitination TAS
Traceable Author Statement
more info
PubMed 
regulation of Rap protein signal transduction IEA
Inferred from Electronic Annotation
more info
 
regulation of platelet-derived growth factor receptor-alpha signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
response to activity IEA
Inferred from Electronic Annotation
more info
 
response to ethanol IEA
Inferred from Electronic Annotation
more info
 
response to gamma radiation IEA
Inferred from Electronic Annotation
more info
 
response to starvation IEA
Inferred from Electronic Annotation
more info
 
response to testosterone IEA
Inferred from Electronic Annotation
more info
 
signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
cilium IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
colocalizes_with flotillin complex ISS
Inferred from Sequence or Structural Similarity
more info
 
focal adhesion IEA
Inferred from Electronic Annotation
more info
 
growth cone IEA
Inferred from Electronic Annotation
more info
 
mast cell granule IEA
Inferred from Electronic Annotation
more info
 
membrane raft IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
E3 ubiquitin-protein ligase CBL
Names
Cas-Br-M (murine) ecotropic retroviral transforming sequence
Cbl proto-oncogene, E3 ubiquitin protein ligase
RING finger protein 55
RING-type E3 ubiquitin transferase CBL
casitas B-lineage lymphoma proto-oncogene
fragile site, folic acid type, rare, fra(11)(q23.3)
oncogene CBL2
proto-oncogene c-Cbl
signal transduction protein CBL
NP_005179.2

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_016808.1 RefSeqGene

    Range
    4997..106870
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_608

mRNA and Protein(s)

  1. NM_005188.3NP_005179.2  E3 ubiquitin-protein ligase CBL

    See identical proteins and their annotated locations for NP_005179.2

    Status: REVIEWED

    Source sequence(s)
    AA806454, AP002956, BC132733, DB457271
    Consensus CDS
    CCDS8418.1
    UniProtKB/Swiss-Prot
    P22681
    Related
    ENSP00000264033.3, ENST00000264033.5
    Conserved Domains (6) summary
    cd09920
    Location:256352
    SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
    cd14393
    Location:857896
    UBA_c-Cbl; UBA domain found in E3 ubiquitin-protein ligase Cbl and similar proteins
    pfam02262
    Location:54175
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:179262
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain
    cd16709
    Location:362427
    RING-HC_Cbl-b; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-b and similar proteins
    cl26464
    Location:480810
    Atrophin-1; Atrophin-1 family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p13 Primary Assembly

    Range
    119206276..119308149
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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