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

    Gene ID: 867, updated on 10-Dec-2024

    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; AllianceGenome:HGNC:1541
    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
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (119206339..119308149)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (119226712..119328785)
    RS_2024_09 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 NHERF family PDZ scaffold protein 4 Neighboring gene small nucleolar RNA, C/D box 150 Neighboring gene dynein regulatory complex subunit 12 homolog Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3973 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3974 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3975 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3976 Neighboring gene fragile site, folic acid type, rare, fra(11)(q23.3) Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5627 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5628 Neighboring gene RNA, U6 small nuclear 262, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119177198-119177943 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:119185831-119186526 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3977 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5629 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119191423-119192048 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119192049-119192674 Neighboring gene uncharacterized LOC124900316 Neighboring gene microRNA 6756 Neighboring gene melanoma cell adhesion molecule

    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

    BioGRID CRISPR Screen Phenotypes (38 hits/1334 screens)

    Associated conditions

    Description Tests
    CBL-related disorder
    MedGen: C3150803 OMIM: 613563 GeneReviews: Not available
    Compare labs
    Juvenile myelomonocytic leukemia
    MedGen: C0349639 OMIM: 607785 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2024-02-14)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2024-02-14)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    New gene functions in megakaryopoiesis and platelet formation.
    EBI GWAS 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 PubChem

    Interactions

    General gene information

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables SH3 domain binding PubMed 
    enables cadherin binding PubMed 
    enables calcium ion binding  
    enables ephrin receptor binding PubMed 
    enables phosphatidylinositol 3-kinase regulatory subunit binding  
    enables phosphotyrosine residue binding  
    enables protein binding PubMed 
    enables receptor tyrosine kinase binding  
    enables ubiquitin protein ligase activity  
    enables ubiquitin protein ligase activity  
    enables ubiquitin-protein transferase activity PubMed 
    Items 1 - 25 of 31
    Process Evidence Code Pubs
    involved_in DNA damage response  
    involved_in cellular response to hypoxia  
    involved_in cellular response to nerve growth factor stimulus  
    involved_in cellular response to platelet-derived growth factor stimulus  
    involved_in cytokine-mediated signaling pathway  
    involved_in male gonad development  
    involved_in mast cell degranulation  
    involved_in negative regulation of apoptotic process PubMed 
    involved_in negative regulation of epidermal growth factor receptor signaling pathway  
    involved_in negative regulation of epidermal growth factor receptor signaling pathway PubMed 
    involved_in negative regulation of epidermal growth factor receptor signaling pathway  
    involved_in positive regulation of epidermal growth factor receptor signaling pathway  
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction PubMed 
    involved_in positive regulation of receptor-mediated endocytosis PubMed 
    involved_in protein autoubiquitination  
    involved_in protein monoubiquitination  
    involved_in protein polyubiquitination  
    involved_in protein ubiquitination PubMed 
    involved_in protein ubiquitination PubMed 
    involved_in protein ubiquitination PubMed 
    involved_in regulation of Rap protein signal transduction  
    involved_in regulation of platelet-derived growth factor receptor-alpha signaling pathway  
    involved_in response to activity  
    involved_in response to ethanol  
    involved_in response to gamma radiation  
    involved_in response to starvation  
    involved_in response to testosterone  
    involved_in signal transduction  
    involved_in symbiont entry into host cell  
    involved_in ubiquitin-dependent endocytosis  
    involved_in ubiquitin-dependent protein catabolic process PubMed 
    Items 1 - 25 of 31
    Component Evidence Code Pubs
    located_in Golgi apparatus PubMed 
    located_in cilium PubMed 
    located_in cytosol  
    located_in cytosol  
    part_of flotillin complex  
    located_in focal adhesion  
    located_in growth cone  
    is_active_in membrane raft  
    located_in perinuclear region of cytoplasm  
    is_active_in plasma membrane  
    located_in plasma membrane PubMed 
    located_in plasma membrane  

    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_005188.4 → NP_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
      A3KMP8, P22681
      UniProtKB/TrEMBL
      A0A0U1RR39
      Related
      ENSP00000264033.3, ENST00000264033.6
      Conserved Domains (6) summary
      cd09920
      Location:256 → 352
      SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
      cd14393
      Location:857 → 896
      UBA_c-Cbl; UBA domain found in E3 ubiquitin-protein ligase Cbl and similar proteins
      pfam02262
      Location:54 → 175
      Cbl_N; CBL proto-oncogene N-terminal domain 1
      pfam02761
      Location:179 → 262
      Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain
      cd16709
      Location:362 → 427
      RING-HC_Cbl-b; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-b and similar proteins
      cl26464
      Location:480 → 810
      Atrophin-1; Atrophin-1 family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      119226712..119328785
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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