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FLASH GENE
Symbol NUMBL contributors: mct - updated : 13-09-2017
HGNC name numb homolog (Drosophila)-like
HGNC id 8061
Location 19q13.2      Physical location : 41.171.813 - 41.196.556
Synonym name
  • numb-related protein
  • numb homolog-like
  • Numb-R
    • Synonym symbol(s) NBL, CAG3A, CTG3A, NUMBR, TNRC23, NUMB-R, NUMBLIKE, NUMB-RIKE,
    DNA
    TYPE functioning gene
    STRUCTURE 24.75 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3561 - 609 - 2017 28067668
    9 - 3483 - 568 - 2017 28067668
    9 - 3367 - 568 - 2017 28067668
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Nervousnerve   highly
    Reproductivefemale systembreastmammary gland   Homo sapiens
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductiveepithelial cell Homo sapiens
    cell lineage neurons
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a phosphotyrosine interaction domain in the N terminus
  • a single NPF (asparagine-proline-phenylalanine) motif
  • putative SH3-binding sites in the C terminus
  • eighteen consecutive glutamine residues
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to Drosophila numb homolog-like
    homolog to C.elegans gene
    homolog to signal transducer Eps15-2 of yeast
    homolog to murine Numbl (95.9pc)
    homolog to rattus Numbl (95.4pc)
    Homologene
    FAMILY
    CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • required for maintaining radial glial adherens junctions, and for the tissue architecture of neurogenic niches and the cerebral cortex
  • negatively regulates NF-kappaB signaling pathways
  • role in neurogenesis suggesting that it may contribute to development of glial tumors
  • NUMB and NUMBL have evolved to acquire at least partially distinct functions
  • implicated in early development of the nervous system
  • played an important role in tumorigenesis and invasion by suppressing NFKB1 activation
  • importance of NUMB and NUMBL in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text neurogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associating with EPS15 and NOTCH1
  • interacting with TAB2 and negatively regulates NF-kappaB signaling pathway
  • LNX1 interacts with the cell fate determinant NUMBL, a Numb homolog-like gene involved in the maintenance of neural progenitor cells during embryonic neurogenesis
  • binding to TRAF6 and promoting its degradation, leading to the inhibition of NF-kappB signaling pathway
  • NUMBL interacted directly with TRAF5, which signals upstream and is required for the activation of NFKB, and committed it to proteasomal degradation by promoting K48-linked polyubiquitination of TRAF5
  • potential novel roles of NUMB/NUMBL in regulating heart trabeculation and compaction by inhibiting NOTCH2 and BMP10 signalling
  • developmental regulator OFCC1 enables polarized integrin localization by modulating NUMB/NUMBL, thus directing the basal constriction that shapes the vertebrate retina epithelium
  • could decrease the expression of TRAF6, CCND1, and MMP9 and increase the expression of CASP3
  • NUMB, NUMBL counteract VEGF receptor degradation and promote VEGFR2 recycling back to the plasma membrane
  • endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae
  • NUMB and NUMBL interacted with small GTPase RAB7A to transition ERBB2 from early to late endosome for degradation
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in human lung cancer cell lines, especially in metastatic cell lines
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    nestin-CreER transgenic mice where Numb/Numbl are removed have severe damage to brain lateral ventricle integrity