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FLASH GENE
Symbol NUMBL contributors: mct - updated : 13-09-2017
HGNC name numb homolog (Drosophila)-like
HGNC id 8061
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