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FLASH GENE
Symbol CBLB contributors: mct - updated : 24-06-2015
HGNC name Cas-Br-M (murine) ecotropic retroviral transforming sequence b
HGNC id 1542
Location 3q13.11      Physical location : 105.377.109 - 105.587.887
Synonym name
  • Casitas B-lineage lymphoma b
    • Synonym symbol(s) FLJ36865, FLJ41152, RNF56, Cbl-b, RNF56, Nbla00127
    DNA
    TYPE functioning gene
    STRUCTURE 214.09 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 3976 - 982 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   highly
    Respiratorylung    
     respiratory tracttrachea  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticgranulocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an UBA domain sufficient to confer the receptor trafficking functions of CBLB on CBL
    • HOMOLOGY
    intraspecies homolog to v-cbl proto-oncogene
    Homologene
    FAMILY Cbl family of E3 ubiquitin (Ub) ligase
    CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • functioning as a negative regulator of T-cell activation
  • E3 ubiquitin ligase having a crucial role in the prevention of chronic inflammation and autoimmunity
  • regulates the TLR4-mediated acute inflammatory response that is induced by sepsis
  • both CBL and CBLB perform regulatory functions in osteoclasts that are unique to one or the other protein (i.e., functions that cannot be compensated by the other homolog)
  • necessary role to prevent the inappropriate activation of NF-B in response to lipopolysaccharide and to polymicrobial sepsis
  • involvement of CBLB in the regulation of osteoblast-related genes expression
  • catalytic function of E3 ligase, CBLB, is essential for negative regulation of T cells
  • plays a crucial role in T cell activation and tolerance induction
  • essential and non-redundant role for CBLB in controlling TGFBR signaling by directly targeting SMAD7 for degradation during T cell responses
  • is critical for establishing the threshold for T cell activation and is essential for induction of T cell anergy
  • ubiquitin ligase (E3) that modulates signaling by tagging molecules for degradation
  • is a type of E3 ubiquitin ligase that interacted with PTK2B, reduced the expression of PTK2B, and promoted trypsin-induced degradation of PTK2B
  • role of CBLB in cell detachment
  • acts as a scaffolding molecule to coordinate the delivery of the BCR and TLR9 into subcellular compartments required for productively delivering BCR-captured ligands to TLR9
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • potentially interacting with signal transduction molecules
  • CBLB would control RUNX2 protein levels at the post-translational event
  • inhibits T cell activation by suppressing PTEN
    • inactivation independently of its ubiquitin ligase activity
  • CLEC4G-mediated signaling up-regulates the threshold of CD4(+) T cell activation via tuning the expression of CBLB
  • AKT2 but not AKT1 regulates FOXP3 expression downstream of CBLB
  • CBLB, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway
  • is also required for entry of the Toll-like receptor 9 (TLR9) into late endosomes
  • CBLB and CBL increased the protein level and stability of SIRT2 and CBLB and CBL interact with SIRT2
  • NFKB1 downregulated CBLB by binding and suppressing CBLB promoter in T cell activation
  • CBLB suppresses ORMDL3 expression through STAT6
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    increases sepsis-induced release of inflammatory cytokines and chemokines
    constitutional       loss of function
    renders T cells hyperresponsive to antigenic stimulation and predisposes individuals toward developing autoimmunity
    Susceptibility
  • to autoimmune diseases
  • to type 1 diabetes in Japanese
  • to multiple sclerosis
    • Variant & Polymorphism SNP , other
  • missense mutations of CBLB in Japanese subjects with type 1 diabetes
  • T allele of rs9657904 within the CBLB gene significantly associated with multiple sclerosis (MS)
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    modulation of the E3 ligase activity of CBLB might be a novel modality to control T cell immunity in vaccination, cancer biology, or autoimmunity
    ANIMAL & CELL MODELS
  • Cblb(-/-) mice are osteopenic, because of increased bone resorption with little compensating increase in bone formation