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CBL Gene

protein-coding   GIFtS: 71
GCID: GC11P119110

Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase

(Previous name: Cas-Br-M (murine) ecotropic retroviral transforming sequence)
(Previous symbol: CBL2)
  See CBL-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase1 2     RING Finger Protein 552 3
CBL21 2 3 5     NSLL2 5
Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence1 2     C-CBL2
Oncogene CBL21 2     FRA11B2
Casitas B-Lineage Lymphoma Proto-Oncogene2 3     E3 Ubiquitin-Protein Ligase CBL2
Proto-Oncogene C-Cbl2 3     Fragile Site, Folic Acid Type, Rare, Fra(11)(Q23.3)2
Signal Transduction Protein CBL2 3     EC 6.3.2.-3
RNF552 3     EC 6.3.28

External Ids:    HGNC: 15411   Entrez Gene: 8672   Ensembl: ENSG000001103957   OMIM: 1653605   UniProtKB: P226813   

Export aliases for CBL gene to outside databases

Previous GC identifers: GC11M121124 GC11P120588 GC11P118614 GC11P118582 GC11P115017


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CBL Gene:
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. Mutations in this gene are also the cause of Noonan syndrome-like disorder. (provided by
RefSeq, Mar 2012)

GeneCards Summary for CBL Gene:
CBL (Cbl proto-oncogene, E3 ubiquitin protein ligase) is a protein-coding gene. Diseases associated with CBL include noonan-like syndrome disorder with or without juvenile myelomonocytic leukemia, and noonan syndrome. GO annotations related to this gene include ubiquitin-protein ligase activity and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is CBLC.

UniProtKB/Swiss-Prot: CBL_HUMAN, P22681
Function: 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

Gene Wiki entry for CBL Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000011.9  NC_018922.2  NT_033899.9  
Regulatory elements:
   Regulatory transcription factor binding sites in the CBL gene promoter:
         Elk-1   AP-1   ATF-2   STAT1beta   STAT5A   STAT1alpha   PPAR-gamma1   STAT3   PPAR-gamma2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCBL promoter sequence
   Search Chromatin IP Primers for CBL

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CBL


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11q23.3   Ensembl cytogenetic band:  11q23.3   HGNC cytogenetic band: 11q23.3

CBL Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CBL gene location

GeneLoc information about chromosome 11         GeneLoc Exon Structure

GeneLoc location for GC11P119110:  view genomic region     (about GC identifiers)

Start:
119,076,752 bp from pter      End:
119,178,859 bp from pter
Size:
102,108 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: CBL_HUMAN, P22681 (See protein sequence)
Recommended Name: E3 ubiquitin-protein ligase CBL  
Size: 906 amino acids; 99633 Da
Subunit: Interacts (phosphorylated at Tyr-731) with PIK3R1. Associates with NCK via its SH3 domain. The
phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with
adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the
highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2.
May interact with CBLB (By similarity). Interacts with ALK, AXL, BLK, FGR and FGFR2. Interacts with CSF1R, EPHB1,
FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN.
Interacts with TEK/TIE2 (tyrosine phosphorylated)
Miscellaneous: This protein has one functional calcium-binding site
Selected PDB 3D structures from and Proteopedia for CBL (see all 21):
1B47 (3D)        1FBV (3D)        1YVH (3D)        2CBL (3D)        2JUJ (3D)        2K4D (3D)    
Secondary accessions: A3KMP8

Explore the universe of human proteins at neXtProt for CBL: NX_P22681

Explore proteomics data for CBL at MOPED

Post-translational modifications: 

  • Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and ZAP70 (By similarity). Phosphorylated on tyrosine
    residues in response to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR and FGR.
    Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Not phosphorylated at Tyr-731 by
    FGFR3. Phosphorylated on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. Phosphorylated on tyrosine
    residues by HCK1
  • Ubiquitinated, leading to its degradation via the proteasome1
  • Ubiquitination2 at Lys7, Lys74, Lys105, Lys424, Lys471, Lys521
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for CBL (P22681) (see all 9)
     LPDTYQHLR  LKNSPPYILD  NPDLTGLCEPTP  LFKEGKERMYEE 


    See CBL Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_005179.2  
    ENSEMBL proteins: 
     ENSP00000264033  
    Reactome Protein details: P22681

    CBL Human Recombinant Protein Products:

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    Novus Biologicals CBL Proteins
    Novus Biologicals CBL Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for CBL 

     
    antibodies-online proteins for CBL (4 products) 

     
    antibodies-online peptides for CBL

    CBL Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of CBL
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    Cell Signaling Technology (CST) Antibodies for CBL 
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    Novus Biologicals CBL Antibodies
    Abcam antibodies for CBL
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for CBL
    LSBio Antibodies in human, mouse, rat for CBL
    antibodies-online antibodies for CBL (222 products) 

    CBL Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for CBL 
    antibodies-online kits for CBL (8 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    RNF: RING-type (C3HC4) zinc fingers

    Selected InterPro protein domains (see all 14):
     IPR001841 Znf_RING
     IPR011992 EF-hand-dom_pair
     IPR014742 Adaptor_Cbl_SH2-like
     IPR024162 Adaptor_Cbl
     IPR013083 Znf_RING/FYVE/PHD

    Graphical View of Domain Structure for InterPro Entry P22681

    ProtoNet protein and cluster: P22681

    3 Blocks protein domains:
    IPB000449 Ubiquitin-associated domain
    IPB001841 Zn-finger
    IPB003153 Adaptor protein Cbl


    UniProtKB/Swiss-Prot: CBL_HUMAN, P22681
    Domain: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme
    Domain: The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the
    RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of
    three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain
    Similarity: Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain
    Similarity: Contains 1 RING-type zinc finger
    Similarity: Contains 1 UBA domain


    Find genes that share domains with CBL           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CBL_HUMAN, P22681
    Function: 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

         Genatlas biochemistry entry for CBL:
    Cas-Br-M (murine) ecotropic retroviral transforming sequence,including a CGG trinucleotide repeat,abundantly
    expressed in thymus,acting as a RING-type E2-dependent ubiquitin protein ligase,binding and stimulating the
    ubiquitination of PDGFRs,EGFR,CSF1R,also interacting with signal transduction molecules,key mediator of HCK
    (hematopoietic cell kinase) induced signaling in hematopoietic cells

         Enzyme Numbers (IUBMB): EC 6.3.2.-1 EC 6.3.22

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001784phosphotyrosine binding IEA--
    GO:0003700sequence-specific DNA binding transcription factor activity TAS2030914
    GO:0004842ubiquitin-protein ligase activity TAS15465819
    GO:0004871signal transducer activity IEA--
    GO:0005509calcium ion binding IEA--
         
    Find genes that share ontologies with CBL           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for CBL:
     Metaphase cells  Synthetic lethal with Ras 

         Selected MGI mutant phenotypes (inferred from 7 alleles(MGI details for Cbl) (see all 20):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  craniofacial 
     endocrine/exocrine gland  growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  liver/biliary system  mortality/aging 

    Find genes that share phenotypes with CBL           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for CBL: Cbltm1Soga Cbltm1Ddlb Cbltm1.1Hua

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CBL
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for CBL

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CBL
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CBL

    miRNA
    Products:
        
    miRTarBase miRNAs that target CBL:
    hsa-let-7c-5p (MIRT051757), hsa-mir-17-5p (MIRT050866)

    Block miRNA regulation of human, mouse, rat CBL using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate CBL (see all 176):
    hsa-miR-26a-2* hsa-miR-520f hsa-miR-605 hsa-miR-502-3p hsa-miR-200b hsa-miR-642b hsa-miR-4326 hsa-miR-3909
    Browse SwitchGear 3'UTR luciferase reporter plasmids
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for CBL
    Predesigned siRNA for gene silencing in human, mouse, rat CBL

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for CBL

    Clone
    Products:
         
    OriGene clones in human, mouse for CBL (see all 6)
    OriGene ORF clones in mouse, rat for CBL
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: CBL (NM_005188)
    Sino Biological Human cDNA Clone for CBL
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CBL
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CBL

    Cell Line
    Products:
         
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    In Situ Assay
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    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA1-12109) for CBL 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CBL_HUMAN, P22681: Cytoplasm. Cell membrane. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytosol4
    nucleus3
    cytoskeleton2
    endosome2
    lysosome2
    vacuole2
    extracellular1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane TAS--
    GO:0016600colocalizes with flotillin complex ISS--

    Find genes that share ontologies with CBL           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CBL About   (see all 73)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1IL-9 Signaling Pathways
    IL-7 Signaling Pathway0.40
    Adipocytokines and Insulin Signaling0.34
    Development Thrombopoietin regulated cell processes0.38
    2Development EGFR signaling pathway
    Development EGFR signaling pathway0.57
    EGF Pathway0.39
    Development ERBB family signaling0.57
    3RANK Signaling in Osteoclasts
    RANK Signaling in Osteoclasts0.45
    RANKL/RANK Signaling Pathway0.31
    RANK Pathway0.38
    4Immune response IFN gamma signaling pathway
    IFN-gamma pathway0.43
    Immune response IFN gamma signaling pathway0.43
    5Development EPO induced Jak STAT pathway
    Development EPO induced Jak STAT pathway0.42
    EPO signaling pathway0.34


    Find genes that share SuperPaths with CBL           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for CBL
        Adipocytokines & Insulin Signaling

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CBL (see all 14)
        FLT3 Signaling
    Internalin Pathway
    Molecular Mechanisms of Cancer
    Ephrin-Eph Signaling
    Rap1 Pathway

    3 Cell Signaling Technology (CST) Pathways for CBL
        Lymphocyte Signaling
    Tyrosine Kinases / Adaptors
    Protein Stability

    Selected GeneGo (Thomson Reuters) Pathways for CBL (see all 15)
        Development EPO-induced MAPK pathway
    Development EGFR signaling pathway
    Development Thrombopoietin-regulated cell processes
    Development EGFR signaling via small GTPases
    Translation Regulation of EIF2 activity

    Selected BioSystems Pathways for CBL (see all 35)
        EGFR1 Signaling Pathway
    Insulin Signaling
    Interferon type I
    Signaling Pathways in Glioblastoma
    IL-5 Signaling Pathway


    Selected Reactome Pathways for CBL (see all 9)
        TGF-beta receptor signaling activates SMADs
    Regulation of signaling by CBL
    Spry regulation of FGF signaling
    EGFR downregulation
    Negative regulation of FGFR signaling


    Selected Kegg Pathways  (Kegg details for CBL) (see all 10):
        ErbB signaling pathway
    Ubiquitin mediated proteolysis
    Endocytosis
    Jak-STAT signaling pathway
    T cell receptor signaling pathway

    UniProtKB/Swiss-Prot: CBL_HUMAN, P22681
    Pathway: Protein modification; protein ubiquitination

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CBL: 

              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Insulin Signaling Pathway in human mouse rat
              EGF / PDGF Signaling Pathway in human mouse rat
              Notch Signaling Pathway in human mouse rat
              Ubiquitin Ligases in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CBL

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CBL (P226811, 2, 3 ENSP000002640334) via UniProtKB, MINT, STRING, and/or I2D (see all 399)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SPRY2O435971, 2, 3, ENSP000003663064EBI-518228,EBI-742487 MINT-6539050 MINT-6539113 MINT-6170575 MINT-6539098 MINT-6539601 MINT-6538989 MINT-6538901 MINT-6169721 MINT-6539083 MINT-6170624 MINT-6539143 MINT-6539038 MINT-8030771 MINT-6539128 MINT-6169688 MINT-6170593 MINT-6539063 I2D: score=4 STRING: ENSP00000366306
    EGFRP005331, 2, 3, ENSP000002754934EBI-518228,EBI-297353 MINT-6170185 MINT-16158 MINT-6539293 MINT-6539009 MINT-6539329 MINT-61493 MINT-6538916 MINT-6539305 MINT-6539317 MINT-6539560 MINT-6539574 MINT-6170566 MINT-60973 MINT-7046383 MINT-60972 MINT-6539341 I2D: score=9 STRING: ENSP00000275493
    METP085811, 2, 3, ENSP000003172724EBI-518228,EBI-1039152 MINT-14027 MINT-16046 MINT-6538928 MINT-6539019 MINT-6539423 MINT-6539387 MINT-6539363 MINT-6539411 MINT-6539399 MINT-6539587 MINT-6539435 MINT-6539375 I2D: score=4 STRING: ENSP00000317272
    YWHAQP273481, 2, 3, ENSP000002380814EBI-518228,EBI-359854 MINT-8006676 MINT-8005073 MINT-7899812 MINT-8005953 MINT-8005087 MINT-8005023 MINT-8005960 MINT-8005080 MINT-8005974 MINT-8005094 MINT-8005885 MINT-8005967 I2D: score=4 STRING: ENSP00000238081
    ARHGEF7Q141551, 2, 3, ENSP000003648934EBI-518228,EBI-717515 MINT-7211968 MINT-7211987 MINT-7211918 MINT-7211864 MINT-7212521 MINT-7211952 MINT-7211842 MINT-7211850 MINT-7212004 I2D: score=2 STRING: ENSP00000364893
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006355regulation of transcription, DNA-templated TAS2030914
    GO:0007166cell surface receptor signaling pathway TAS15465819
    GO:0007173epidermal growth factor receptor signaling pathway TAS15465819
    GO:0007179transforming growth factor beta receptor signaling pathway TAS--
    GO:0008543fibroblast growth factor receptor signaling pathway TAS--

    Find genes that share ontologies with CBL           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for CBL

    5 HMDB Compounds for CBL    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    CalciumCa (see all 2)7440-70-2--
    Phosphoric acidacide phosphorique (FRENCH) (see all 20)7664-38-2--
    Pyrophosphate(4-)Diphosphoric acid ion (see all 10)14000-31-8--

    Selected Novoseek inferred chemical compound relationships for CBL gene (see all 38)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 85 520 9210408 (8), 8920860 (7), 10204582 (6), 9535867 (6) (see all 99)
    phosphatidylinositol 66.9 71 15581361 (6), 14640702 (5), 7791764 (4), 8612729 (3) (see all 31)
    phosphotyrosine 65.3 18 8995358 (2), 9988765 (2), 10490604 (2), 15465819 (1) (see all 11)
    piceatannol 61.3 1 12435267 (1)
    thiosemicarbazide 49.9 3 8900205 (1), 10779765 (1), 8626543 (1)
    convulxin 46.5 1 9153205 (1)
    geldanamycin 46.2 2 12574167 (1)
    ag 1478 43.6 1 19947936 (1)
    lactacystin 39.9 1 12829707 (1)
    phosphoinositide 36.2 7 11042121 (2), 10940298 (1), 14530346 (1), 9794375 (1) (see all 5)



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    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for CBL gene: 
    NM_005188.3  

    Unigene Cluster for CBL:

    Cbl proto-oncogene, E3 ubiquitin protein ligase
    Hs.504096  [show with all ESTs]
    Unigene Representative Sequence: NM_005188
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000264033(uc001pwe.3)
    miRNA
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    Additional mRNA sequence: 

    AK092300.1 AL832396.1 BC132733.1 BC136463.1 BX648139.1 X57110.1 X69207.1 

    5 DOTS entries:

    DT.453210  DT.120727695  DT.210757  DT.103199  DT.95368792 

    18 AceView cDNA sequences:

    BE550582 NM_005188 AW015807 X69207 AL110451 AI808688 AI206156 BX106739 
    AI633902 AA972853 X57110 AL712494 AI963960 BG722940 BF801902 BF752017 
    AW935681 BF894352 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CBL expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TCTGTAAAAA
    CBL Expression
    About this image


    CBL expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Limb (Muscoskeletal System)
             Limb Bud Mesenchyme Cells Limb Bud
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Placenta (Extraembryonic Tissues)
             Hofbauer Cells Chorionic Villus
     
     Mesoderm (Gastrulation Derivatives)
             Limb Bud Mesenchyme Cells Limb Bud
     
     Chorion (Extraembryonic Tissues)
             Hofbauer Cells Chorionic Villus
    CBL Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CBL Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.504096
        Pathway & Disease-focused RT2 Profiler PCR Arrays including CBL: 
              Ubiquitination (Ubiquitylation) Pathway in human mouse rat
              Insulin Signaling Pathway in human mouse rat
              EGF / PDGF Signaling Pathway in human mouse rat
              Notch Signaling Pathway in human mouse rat
              Ubiquitin Ligases in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for CBL gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cbl1 , 5 Casitas B-lineage lymphoma1, 5 88.08(n)1
    93.02(a)1
      9 (24.72 cM)5
    124021  NM_007619.21  NP_031645.21 
     441492625 
    chicken
    (Gallus gallus)
    Aves CBL1 Cbl proto-oncogene, E3 ubiquitin protein ligase 77.65(n)
    85.63(a)
      374038  NM_204208.1  NP_989539.1 
    lizard
    (Anolis carolinensis)
    Reptilia CBL6
    Cbl proto-oncogene, E3 ubiquitin protein ligase
    80(a)
    1 ↔ 1
    GL343797.1(168280-199197)
    African clawed frog
    (Xenopus laevis)
    Amphibia Cbl2 Cbl proto-oncogene protein 76.21(n)    AF237765.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cbl1 Cas-Br-M (murine) ecotropic retroviral transforming more 68.48(n)
    73.78(a)
      492364  NM_001007330.1  NP_001007331.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Cbl3 dorsal/ventral axis determination,
    follicular more
    71(a)   3 66C12   --
    worm
    (Caenorhabditis elegans)
    Secernentea sli-13 adaptor-like E3 ubiquitin ligase 54(a)   X(756037-761201)   --


    ENSEMBL Gene Tree for CBL (if available)
    TreeFam Gene Tree for CBL (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CBL gene
    CBLC2  CBLB2  
    3 SIMAP similar genes for CBL using alignment to 2 protein entries:     CBL_HUMAN (see all proteins):
    CBLC    CBLB    TRIM39

    Find genes that share paralogs with CBL           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CBL (see all 2081)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 11 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0643344
    Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)4--see VAR_0643342 D Y mis40--------
    VAR_0643324
    Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)4--see VAR_0643322 Q P mis40--------
    VAR_0643354
    Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)4--see VAR_0643352 R Q mis40--------
    VAR_0643334
    Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)4--see VAR_0643332 K E mis40--------
    rs2676067081,2
    Cpathogenic1119013936(+) CTGCCA/GATGTG 2 Q R mis10--------
    rs3776666581,2
    C--115024113(+) CGTCT-/CCAAAA 1 -- int10--------
    rs1127129911,2
    C--115030472(+) GTCTC-/AAAAAA 1 -- int11Minor allele frequency- A:0.50CSA 2
    rs1129177071,2
    F--115030783(+) TTTTTT/GTTTTT 1 -- int12Minor allele frequency- G:0.22CSA WA 119
    rs116018211,2
    C,H--115056290(+) TTTTTT/GTTTTT 1 -- int1 trp31Minor allele frequency- G:0.25NA 4
    rs113137491,2
    C,F--115063869(+) TGGGAG/-GGCTG 1 -- int14Minor allele frequency- -:0.50NA CSA 8

    HapMap Linkage Disequilibrium report for CBL (119076752 - 119178859 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for CBL:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2665710CNV Deletion23128226
    esv1143209CNV Insertion17803354
    esv2519793CNV Insertion19546169
    nsv525043CNV Loss19592680
    nsv898417CNV Loss21882294
    nsv898418CNV Loss21882294
    nsv528636CNV Gain19592680

    Human Gene Mutation Database (HGMD): CBL
    Selected Site Specific Mutation Identification with PCR Assays for CBL (see all 12):
    Cosmic IdAA Change
    34066p.C384Y
    34052p.Y371H
    34077p.R420Q
    34057p.C384R
    41789p.C416Y
    5 Site Specific Cancer Mutation PCR Panels containing CBL:
    Tyrosine Kinases & Cell Signaling Pathways Panel 384HT
    Cancer Comprehensive Panel 384HT
    Oncogene Panel 384HT
    Myelodysplastic Syndromes
    Tumor Suppressor Panel 384HT
    SeqTarget long-range PCR primers for resequencing CBL
    DNA2.0 Custom Variant and Variant Library Synthesis for CBL

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 165360   
    OMIM disorders: 613563  
    UniProtKB/Swiss-Prot: CBL_HUMAN, P22681
  • Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:613563]: A
    syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable,
    including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities
    with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set
    ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for
    certain malignancies, particularly juvenile myelomonocytic leukemia. Note=The disease is caused by mutations
    affecting the gene represented in this entry

  • 8 diseases for CBL:    
    About MalaCards
    noonan-like syndrome disorder with or without juvenile myelomonocytic leukemia    noonan syndrome    jacobsen syndrome    pernicious anemia
    juvenile myelomonocytic leukemia    thanatophoric dysplasia    saethre-chotzen syndrome    methylmalonic acidemia

    5 diseases from the University of Copenhagen DISEASES database for CBL:
    Vitamin B12 deficiency     Methylmalonic acidemia     Pernicious anemia     Lymphoma
    Leukemia

    Find genes that share disorders with CBL           About GenesLikeMe

    Selected Novoseek inferred disease relationships for CBL gene (see all 16)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    myeloid leukemia 38.7 2 7545163 (1), 19734451 (1)
    myeloid leukemia chronic 29.5 3 9845379 (1), 12764153 (1), 18235045 (1)
    lymphoma 27 10 17704644 (1), 14530346 (1), 16289966 (1), 17391982 (1) (see all 8)
    wiskott-aldrich syndrome 17.9 2 8810341 (1), 10427990 (1)
    leukemia 17.5 5 7545163 (1), 9845379 (1), 18974118 (1), 11684286 (1) (see all 5)
    leukemia t-cell 12.8 1 2030914 (1)
    acute leukemia 12.3 1 12764153 (1)
    cancer 5.23 6 10891544 (2), 18632619 (1), 16227975 (1), 19901108 (1)
    metastasis 5.03 3 14991403 (3)
    necrosis 3.42 2 15562428 (1)

    Genetic Association Database (GAD): CBL
    Human Genome Epidemiology (HuGE) Navigator: CBL (18 documents)

    Export disorders for CBL gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CBL gene, integrated from 10 sources (see all 754):
    (articles sorted by number of sources associating them with CBL)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases. (PubMed id 9535867)1, 2, 9 Deckert M.... Liu Y.C. (J. Biol. Chem. 1998)
    2. Fgr but not Syk tyrosine kinase is a target for beta 2 integrin- induced c-Cbl-mediated ubiquitination in adherent human neutrophils. (PubMed id 12435267)1, 2, 9 Melander F.... Dib K. (Biochem. J. 2003)
    3. APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. (PubMed id 11997497)1, 2, 9 Liu J.... Saltiel A.R. (Mol. Cell. Biol. 2002)
    4. APS, an adaptor protein containing pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl. (PubMed id 10374881)1, 2, 9 Wakioka T....Yoshimura A. (Leukemia 1999)
    5. APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis. (PubMed id 9989826)1, 2, 9 Yokouchi M.... Yoshimura A. (Oncogene 1999)
    6. Ligand binding induces Cbl-dependent EphB1 receptor degradation through the lysosomal pathway. (PubMed id 18034775)1, 2, 9 Fasen K.... Huynh-Do U. (Traffic 2008)
    7. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2- dependent ubiquitin-protein ligase. (PubMed id 10514377)1, 2, 9 Joazeiro C.A....Liu Y.-C. (Science 1999)
    8. Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein stability in imatinib-resistant chronic myelogenous leukemia cells. (PubMed id 18235045)1, 2, 9 Wu J....Donato N.J. (Blood 2008)
    9. Binding of Cbl to a phospholipase Cgamma1-docking site on platelet- derived growth factor receptor beta provides a dual mechanism of negative regulation. (PubMed id 17620338)1, 2, 9 Reddi A.L.... Band H. (J. Biol. Chem. 2007)
    10. Catalytic domains of tyrosine kinases determine the phosphorylation sites within c-Cbl. (PubMed id 15556646)1, 2, 9 Grossmann A.H.... Druker B.J. (FEBS Lett. 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 867 HGNC: 1541 AceView: CBL Ensembl:ENSG00000110395 euGenes: HUgn867
    ECgene: CBL Kegg: 867 H-InvDB: CBL

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for CBL Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CBL Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CBL gene:
    Search GeneIP for patents involving CBL

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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