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FLASH GENE
Symbol NEDD9 contributors: mct - updated : 22-04-2011
HGNC name neural precursor cell expressed, developmentally down-regulated 9
HGNC id 7733
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a SH3 domain interacting with two proline-rich regions of focal adhesion kinase and a substrate domain
  • multiple SH2-binding motifs
  • a C-terminal domain containing a divergent helix-loop-helix (hlh) motif
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to rattus Nedd9 (87.5pc)
    ortholog to murine Nedd9 (89.2pc)
    Homologene
    FAMILY CAS family
    CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text different location in fibroblasts and in epithelial cells, predominantly in nucleus and in the cell periphery respectively
  • recruited to the centrosome during cell cycle progression
  • basic FUNCTION
  • focal adhesion-associated signaling protein that undergoes a striking relocalization to the spindle at mitosis
  • cell-cycle regulated proteine kinase required for regulation of centrosome structure at the G/M transition
  • playing a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion
  • may be an important linking element between extracellular signaling and regulation of the cytoskeleton
  • playing an important role in the pathophysiology of rheumatoid arthritis
  • regulating activation of AURKA and NEK at the centrosome
  • enhanced invasion in vitro and metastasis in vivo of both normal and transformed melanocytes
  • with ARHGAP22, DOCK3, WASF2, are key molecules regulating RAC1 and RHO signaling that determine the mode of movement driving melanoma cell metastasis
  • promotes the migration of neural crest cells in a graded manner and suggest a role for retinoic acid in the control of NEDD9 expression levels (
  • required for VEGF-mediated head and neck squamous cell carcinoma (HNSCC) cell migration and invasion, consistent with its recent identification as a metastatic regulator (
  • act as scaffolds to regulate protein complexes controlling migration and chemotaxis, apoptosis, cell cycle, and differentiation, and is linked to a role in progenitor cell function
  • important role for CAS proteins in cell-cell adhesion signaling in development
  • role of NEDD9 as a mediator of the canonical Wnt/CTNNB signaling pathway for cell proliferation, migration, and tumorigenesis, as well as an important player in colorectal tumorigenesis and progression
  • new role for CAS proteins in cell-cell adhesion signaling in cancer
  • CELLULAR PROCESS cell cycle, progression
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the cell division control machinery
  • CAS scaffolding proteins (NEDD9, BCAR1, and CASS4) regulate cell migration, division and survival, and are often deregulated in cancer
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PTK2
  • NICAL
  • interacting with RHOA (impairs M-phase progression by disrupting the RhoA activation cycle)
  • interacting with SH2D3C (constitutively bound to NEDD9 in B cells and this association is required for NEDD9 serine/threonine phosphorylation)
  • novel Wnt signaling target
  • cell & other
    REGULATION
    activated by induction of cell growth
    WNT3A, CTNNB, and DVL2 in a dose-dependent manner
    induced by two xenobiotic responsive elements present in its promoter
    inhibited by PTPN11 (PTPN11 inhibits tyrosine phosphorylation of Crk-associated substrate lymphocyte type (NEDD9)) (
    Other regulated by TGF-beta1
    phosphorylation dependent on cell adhesion and Src kinase activity
    association with SH2D3C in B cells required for the generation of the hyperphosphorylated p115 CASL (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    contributes to the metastatic behavior of melanoma and glioblastoma cells
    tumoral     --over  
    in colorectal tumor tissues, increased with the tumor grade
    Susceptibility to late-onset Alzheimer and Parkinson disease
    Variant & Polymorphism SNP
  • associated with late-onset Alzheimer's and Parkinson's disease (minor role)
  • significant association of a common single nucleotide polymorphism (SNP) rs760678 gene with predisposition to late-onset Alzheimer disease (
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS