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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CBL Gene

protein-coding   GIFtS: 70
GCID: GC11P119110

Cbl proto-oncogene, E3 ubiquitin protein ligase

(Previous name: Cas-Br-M (murine) ecotropic retroviral transforming sequence...)
(Previous symbol: CBL2)
 Explore 47 diseases affiliated with
CBL via
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 Human Malady Compendium 
Biological research products
for CBL    

Aliases
for CBL gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase1 2     C-CBL2
CBL21 2 3 5     FRA11B2
RNF551 2 3     NSLL2
Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence1 2     E3 Ubiquitin-Protein Ligase CBL2
Casitas B-Lineage Lymphoma Proto-Oncogene2 3     Fragile Site, Folic Acid Type, Rare, Fra(11)(Q23.3)2
Proto-Oncogene C-Cbl2 3     Oncogene CBL22
Signal Transduction Protein CBL2 3     EC 6.3.2.-3
RING Finger Protein 552 3     EC 6.3.28
C-Cbl1     

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


Summaries
for CBL gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for CBL:
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)

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 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

Gene Wiki entry for CBL


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000011.9  NC_018922.1  NT_033899.8  
Regulatory elements:
   SABiosciences 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 plasmid: CBL promoter sequence
   Search SABiosciences Chromatin IP Primers for CBL

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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-qter

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

Proteins
for CBL gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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)
Subcellular location: Cytoplasm. Cell membrane. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane
Miscellaneous: This protein has one functional calcium-binding site
6/20 PDB 3D structures from and Proteopedia for CBL (see all 20):
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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P22681

    • 4/9 DME Specific Peptides for CBL (P22681) (see all 9)
     LPDTYQHLR  LKNSPPYILD  NPDLTGLCEPTP  LFKEGKERMYEE 

    CBL Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_005179.2  
    ENSEMBL proteins: 
     ENSP00000264033  
    Reactome Protein details: P22681
    Human Recombinant Protein Products: 
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    Novus Biologicals CBL Proteins
    Novus Biologicals CBL Lysates
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    Browse ProSpec Recombinant Proteins
    Uscn Proteins for CBL

    Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view):    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--


    CBL for ontologies           About GeneDecksing



    CBL Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of CBL
    R&D Systems Antibodies for CBL
    Cell Signaling Technology (CST) Antibodies for CBL 
    OriGene Antibodies (see all 7): CBL
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    GenScript Superior Antibodies for CBL
    Novus Biologicals CBL Antibodies
    Abcam antibodies for CBL 
    Uscn Antibodies for CBL
    ThermoFisher Antibody for CBL

    Assay Products for CBL: 
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    Uscn ELISAs and CLIAs for CBL

    Protein Domains /
    Families
    for CBL gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    CBL for domains           About GeneDecksing

    5/14 InterPro domains/families (see all 14):
     IPR001841 Znf_RING
     IPR011992 EF-hand-like_dom
     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 families:
    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


    Function
    for CBL gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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 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

         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

    miRNA
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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CBL
    8/176 QIAGEN miScript miRNA 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:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CBL (see all 4)
    OriGene shRNA RFP: CBL
    Browse OriGene siRNA
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CBL

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

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CBL (see all 2)
    OriGene untagged cDNA clones in CMV expression vector in human, 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)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CBL 

    Cell Line
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    Search LifeMap BioReagents cell lines for CBL

    In Situ Assay
    Products:       
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    Gene Ontology (GO): 5/9 molecular function terms (GO ID links to tree view) (see all 9):    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 TAS--
    GO:0004871signal transducer activity IEA--
    GO:0005509calcium ion binding IEA--


    CBL for ontologies           About GeneDecksing


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

    Animal Models:
         Mouse knock-outs for CBL: Cbltm1Soga Cbltm1Ddlb Cbltm1.1Hua
         15/20 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  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  integument  limbs/digits/tail  liver/biliary system  mortality/aging 

    CBL for phenotypes           About GeneDecksing


    Pathways & Interactions
    for CBL gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/75 super-pathways (see all 75) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Development HGF signaling pathway
    		Development_EGFR signaling via small GTPases0.44
    		Development_EGFR signaling via PIP30.26
    		Development EGFR signaling via small GTPases0.44
    		Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)0.23
    		Development EGFR signaling via PIP30.26
    2Development FGFR signaling pathway
    		Development FGFR signaling pathway1.00
    		Development_Flt3 signaling0.45
    		Development_FGFR signaling pathway0.98
    		Development Flt3 signaling0.45
    3Signaling by FGFR
    		Signaling by FGFR1.00
    		Signaling by EGFR0.84
    		Signaling by FGFR in disease0.91
    		Signaling by EGFR in Cancer0.83
    4IL-9 Signaling Pathways
    		IL-7 Signaling Pathway0.38
    		Development_Thrombopoietin-regulated cell processes0.36
    		Development Thrombopoietin-regulated cell processes0.36
    		Adipocytokines & Insulin Signaling0.33
    5Development_Prolactin receptor signaling
    		Development_Prolactin receptor signaling1.00
    		Prolactin Signaling Pathway0.39
    		Development Prolactin receptor signaling1.00

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    5/16 EMD Millipore Pathways for CBL (see all 16)
        Chemotaxis CXCR4 signaling pathway
    Immune response CD16 signaling in NK cells
    Development EGFR signaling via PIP3
    Translation Regulation activity of EIF2
    Common schema of ubiquitination

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

    5/14 Downloadable PowerPoint Slides of QIAGEN 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

    5/15 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

    5/34 BioSystems Pathways for CBL (see all 34) 
        Signaling Pathways in Glioblastoma
    EGFR1 Signaling Pathway
    Prolactin Signaling Pathway
    IL-5 Signaling Pathway
    IL-3 Signaling Pathway

    5/25        Reactome Pathways for CBL (see all 25)
        Regulation of signaling by CBL
    Signaling by EGFR in Cancer
    CBL ubiquitinates PI3K
    Disease
    EGFR downregulation


    5/9         Kegg Pathways  (Kegg details for CBL) (see all 9):
        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


    CBL for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for CBL

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

    5/383 Interacting proteins for CBL (P226811, 2, 3 ENSP000002640334) via UniProtKB, MINT, STRING, and/or I2D (see all 383)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    EGFRP005331, 2, 3, ENSP000002754934EBI-518228,EBI-297353 MINT-6170185 MINT-16158 MINT-6539293 MINT-6539009 MINT-6539329 MINT-61493 MINT-6539305 MINT-6538916 MINT-6539317 MINT-6539560 MINT-6539574 MINT-6170566 MINT-60973 MINT-7046383 MINT-6539341 MINT-60972 I2D: score=9 STRING: ENSP00000275493
    GRB2P629931, 2, 3, ENSP000003390074EBI-518228,EBI-401755 MINT-65972 MINT-60974 MINT-6169721 MINT-60977 MINT-7040249 MINT-65979 MINT-6539462 MINT-65973 I2D: score=10 STRING: ENSP00000339007
    SPRY2O435972, 3, ENSP000003663064MINT-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
    METP085812, 3, ENSP000003172724MINT-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
    YWHAQP273482, 3, ENSP000002380814MINT-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
    About this table

    Gene Ontology (GO): 5/9 biological process terms (GO ID links to tree view) (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006355regulation of transcription, DNA-dependent TAS2030914
    GO:0007166cell surface receptor signaling pathway TAS15465819
    GO:0007173epidermal growth factor receptor signaling pathway TAS--
    GO:0008543fibroblast growth factor receptor signaling pathway TAS--
    GO:0014068positive regulation of phosphatidylinositol 3-kinase cascade IMP17003487


    CBL for ontologies           About GeneDecksing



    Drugs & Compounds
    for CBL gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    CBL for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
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    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--
    10/38 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about CBL 

    Transcripts
    for CBL gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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
    Products:             		 OriGene 3'-UTR Clone: CBL
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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CBL
    8/176 QIAGEN miScript miRNA 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
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    Additional cDNA 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:

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

    GeneLoc Exon Structure


    Expression
    for CBL gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    CBL expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: TCTGTAAAAA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    CBL expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    4 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    LimbLimb BudLimb Bud Mesenchyme CellsMesoderm
    PlacentaChorionic VillusHofbauer CellsExtraembryonic Tissues, Placenta
    Skeletal MuscleHyoid Arch MusclesMononuclear MyocytesSkeletal Muscle
    Skeletal MuscleMandibular Arch MusclesMononuclear MyocytesSkeletal Muscle
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See CBL Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for CBL

    SOURCE GeneReport for Unigene cluster: Hs.504096
        SABiosciences Expression via Pathway-Focused 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

    Primer
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    In Situ
    Assay Products:     
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    Orthologs
    for CBL gene

    (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)
    About This Section
    This gene was present in the common ancestor of animals.

    Orthologs for CBL gene from 6/22 species (see all 22)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves CBL1 Cas-Br-M (murine) ecotropic retroviral transforming more 77.83(n)
    86.04(a)    		   374038  NM_204208.1  NP_989539.1 
    lizard
    (Anolis carolinensis)    		 Reptilia CBL6
    		 --
    		 82(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 68.45(n)
    74.43(a)    		   492364  NM_001007330.1  NP_001007331.1 
    fruit fly
    (Drosophila melanogaster)    		 Insecta Cbl1 , 3 dorsal/ventral axis determination,
    follicular more3
    CG7037-PA1    		 71(a)3
    53.29(n)1
    50.82(a)1    		   3 66C123
    389611  NM_139967.11  NP_648224.11 
    worm
    (Caenorhabditis elegans)    		 Secernentea sli-11 , 3 adaptor-like E3 ubiquitin ligase3
    Protein SLI-11    		 54(a)3
    55.19(n)1
    51.21(a)1    		   X(756037-761201)3
    1804191  NM_001029627.11  NP_001024798.11 


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

    Paralogs
    for CBL gene

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

    CBL for paralogs           About GeneDecksing



    Genomic Variants
    for CBL gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1670 NCBI SNPs in CBL are shown (see all 1670)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 11 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs71269711,2
    		C--115015950(+) AACTAG/AGTGTT 1 -- us2k12Minor allele frequency- A:0.00NA 4
    rs71271301,2
    		C--115016107(+) ACCCAG/AGATGC 1 -- us2k12Minor allele frequency- A:0.00NA 4
    rs795460261,2
    		C,--115016114(+) ATGCCT/AGTCTG 1 -- us2k13Minor allele frequency- A:0.07WA 122
    rs2021810731,2
    		C--115017023(+) CCCCAA/CCNNNN 1 -- us2k10--------
    rs755409201,2
    		F,--115018280(+) ACATAT/CTGATG 1 -- int11Minor allele frequency- C:0.06WA 118
    rs1121008791,2
    		C,--115018282(+) ATATTG/TATGTT 1 -- int11Minor allele frequency- T:0.50NA 2
    rs178488931,2
    		C,--115018496(+) TCCTCC/TCTACT 1 -- int1 trp30--------
    rs118287011,2
    		C,F,H,--115018988(+) AATAAA/GATGAT 1 -- int15Minor allele frequency- G:0.09WA NA 128
    rs1159523741,2
    		C,F,--115019189(+) ACTAAT/CTTTAT 1 -- int11Minor allele frequency- C:0.03WA 118
    rs25089461,2
    		H--115019410(+) GGTGCA/CGTACA 1 -- int14Minor allele frequency- C:0.00NS EA 418

    HapMap Linkage Disequilibrium report for CBL (119076752 - 119178859 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for CBL
         1 Indel: 101350
    Human Gene Mutation Database (HGMD): CBL

    5/12 SABiosciences Cancer Mutation PCR Assays for CBL (see all 12):
    Cosmic IdAA Change
    34066p.C384Y
    34052p.Y371H
    34077p.R420Q
    34057p.C384R
    41789p.C416Y
    5 SABiosciences Cancer Mutation PCR Arrays containing CBL:
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    Cancer Comprehensive Panel 384HT
    Oncogene Panel 384HT
    Myelodysplastic Syndromes
    Tumor Suppressor Panel 384HT
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing CBL
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    Disorders / Diseases
    for CBL gene

    (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.)
    About This Section
    CBL for disorders           About GeneDecksing

    OMIM gene information: 165360   
    OMIM disorders: 613563  
    UniProtKB/Swiss-Prot: CBL_HUMAN, P22681
  • Defects in CBL are the cause of 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

    20/47 diseases for CBL (see all 47):    About MalaCards
    noonan syndrome-like disorder    noonan syndrome    saethre-chotzen syndrome    wiskott-aldrich syndrome
    juvenile myelomonocytic leukemia    thanatophoric dysplasia    pernicious anemia    myeloid leukemia
    myelomonocytic leukemia    megaloblastic anemia    jacobsen syndrome    b-cell lymphomas
    systemic lupus erythematosus    acute promyelocytic leukemia    lupus erythematosus    hepatitis e
    leukemia    chronic lymphocytic leukemia    acute myeloid leukemia    chronic myeloid leukemia

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

    10/16 Novoseek 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)

    Human Genome Epidemiology (HuGE) Navigator: CBL (18 documents)

    Export disorders for CBL gene to outside databases

    Publications
    for CBL gene

    (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)
    About This Section

    PubMed articles for CBL gene, integrated from 9 sources (see all 716):
    (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. (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. (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. (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. (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. (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. (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. (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. (2008)
    9. Binding of Cbl to a phospholipase Cgamma1-docking sit e 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. (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. (2004)

    External Searches for CBL gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing CBL gene

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

    Other Databases showing CBL gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing CBL gene

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

    Intellectual Property
    for CBL gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		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



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    About This Section

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