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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
Location 6p24.2      Physical location : 11.183.530 - 11.382.581
Synonym name
  • Crk-associated substrate related
  • cas-like docking
  • enhancer of filamentation 1
  • Synonym symbol(s) HGNC7733, HEF1, CAS-L, CASL, CAS2, CASL, CASS2
    DNA
    TYPE functioning gene
    STRUCTURE 199.05 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    OFCC1 6p24.3 orofacial cleft 1 candidate 1 LOC346096 6p24.1 similar to Rpl7a protein LOC391868 6 similar to 60S ribosomal protein L21 LOC391869 6 similar to ribosomal protein L7-like 1 TFAP2A 6p24.3-p24.2 transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha) MGC40222 6p24.1 hypothetical protein MGC40222 MRPL48P1 6p24.1 mitochondrial ribosomal protein L48 pseudogene 1 GCNT2 6p24.1 glucosaminyl (N-acetyl) transferase 2, I-branching enzyme LOC389366 6 similar to C6orf52 protein PAK1IP1 6p24.1 PAK1 interacting protein 1 C6orf53 6p24.1 chromosome 6 open reading frame 53 TMEM14B 6p25.1-p23 transmembrane protein 14B MAK 6q22 male germ cell-associated kinase GCM2 6p23 glial cells missing homolog 2 (Drosophila) LOC221711 6p24.1 hypothetical protein LOC221711 ELOVL2 6p22.3 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 2 LOC389367 6 LOC389367 LOC389368 6 similar to hypothetical protein D930020E02 NEDD9 6p25-p24 neural precursor cell expressed, developmentally down-regulated 9 C6orf105 6p24.1 chromosome 6 open reading frame 105 LOC389369 6 LOC389369 HIVEP1 6p24.1 human immunodeficiency virus type I enhancer binding protein 1 EDN1 6p24.1 endothelin 1 RPEL1 6p23 RPEL repeat containing 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 4550 92.9 834 - 1996 8879209
    - - 1329 - 174 - 1996 8879209
    8 - 4745 92.9 834 - 1996 8879209
    - - - 115 - - 2010 20956287
  • hyperphosphorylated isoform, p115 CASL is likely necessary for the integration of BCR and S1P-dependent integrin signaling that permits MZ(marginal zone) B cells to be retained in the MZ, whereas dephosphorylation of CASLL contributes to cell detachment and trafficking to the follicle
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineplacenta   highly
    Nervousbrain    
    Respiratorylung   highly
    Urinarykidney   highly
    Visualeyelacrimal gland   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsensoryolfactory  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    Lymphoid/Immunelymphocyte
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    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