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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
    Physical map
    MAIL 3p12-q12 molecule possessing ankyrin repeats induced by lipopolysaccharide (MAIL), homolog of mouse LOC131368 3q13.11 hypothetical protein LOC131368 LOC391561 3 similar to MLRQ subunit of the NADH: ubiquinone oxidoreductase complex LOC391562 3 similar to villin 2; ezrin; cytovillin ALCAM 3q13.1-q13.2 activated leukocyte cell adhesion molecule CBLB 3q21-q25 Cas-Br-M (murine) ecotropic retroviral transforming sequence b LOC344593 3q13.12 similar to protein tyrosine phosphatase, non-receptor type 11; protein-tyrosine phosphatase 2C; Noonan syndrome 1 LOC344595 3q13.12 hypothetical LOC344595 LOC391563 3 similar to citrate synthase (51.5 kD) (3L304) NYD-SP17 3q13.12 testes development-related NYD-SP17 BBX 3q13.1 bobby sox homolog (Drosophila) LOC285205 3q13.12 hypothetical protein LOC285205 CD47 3q13.1-q13.2 CD47 antigen (Rh-related antigen, integrin-associated signal transducer) ESRRBL1 3q13.13 estrogen-related receptor beta like 1 HHLA2 3q13.13 HERV-H LTR-associating 2 KIAA1000 3q13.13 HERV-H LTR-associating 2 KIAA1524 3q13.13 KIAA1524 protein DZIP3 3q13.1-q13.2 KIAA1524 protein RETNLB 3q13.1 resistin like beta TRIM 3q13 resistin like beta GUCA1C 3q13.1 guanylate cyclase activator 1C MORC 3q13 microrchidia homolog (mouse) LOC151871 3q13.13 hypothetical protein BC018070
    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