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

    Gene ID: 867, updated on 8-Jul-2021

    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
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    Genomic context

    See CBL in Genome Data Viewer
    Location:
    11q23.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 11 NC_000011.10 (119206339..119308149)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (119077049..119178859)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 11099 Neighboring gene coiled-coil domain containing 153 Neighboring gene fragile site, folic acid type, rare, fra(11)(q23.3) 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 Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Juvenile myelomonocytic leukemia
    MedGen: C0349639 OMIM: 607785 GeneReviews: Not available
    Compare labs
    New gene functions in megakaryopoiesis and platelet formation.
    GeneReviews: Not available
    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

    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 PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

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

    NEW Try the new Transcript table

    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_005188.4NP_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, ENST00000264033.6
      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 Updated Annotation Release 109.20210514

    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
      119206339..119308149
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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