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FLASH GENE
Symbol NET1 contributors: mct - updated : 25-05-2011
HGNC name neuroepithelial cell transforming gene 1
HGNC id 14592
Location 10p15      Physical location : 5.454.517 - 5.500.424
Synonym name
  • guanine nucleotide regulatory protein (oncogene)
  • Rho guanine nucleotide exchange factor (GEF) 8
  • p65 Net1 proto-oncogene protein
  • Synonym symbol(s) NET1A, ARHGEF8, RP11-116G8.1
    DNA
    TYPE functioning gene
    STRUCTURE 45.91 kb     12 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
    12 - 3414 67.7 596 - 2013 23184663
  • NET1
  • RAC1 activation causes relocalization of NET1 isoforms outside the nucleus and stimulates NET1A catalytic activity
  • 10 - 3297 - 542 - 2013 23184663
  • NET1A
  • RAC1 activation causes relocalization of NET1 isoforms outside the nucleus and stimulates NET1A catalytic activity
  • NET1A, but not NET1, is required for cell spreading on collagen, myosin light chain phosphorylation, and focal adhesion maturation
  • role for NET1A in regulating cell adhesion.
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestiveesophagus   highly
     mouth   highly
    Respiratoryrespiratory tracttrachea  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text highly in placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • guanine nucleotide exchange factor domain
  • a PH domain
  • Rho GEF domain
  • a DBL homology domain (DH)
  • a potential PDZ binding site in the C terminus critical to its ability to transform cells, but not required for enzymatic activity or for effects on the actin cytoskeleton
  • HOMOLOGY
    interspecies homolog to murine Net1
    Homologene
    FAMILY
    CATEGORY protooncogene , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • predominantly localizes to the cell nucleus at steady-state (
  • basic FUNCTION
  • guanine nucleotide exchange factors (GEFs) specific for RhoA, but not CDC42 or RAC1
  • having ability to stimulate cytoskeletal reorganization and to transform cells
  • acting as guanine nucleotide exchange factor (GEF) for RhoA GTPase
  • may be involved in activation of the SAPK/JNK pathway
  • importance of NET1 in controlling RHOA and MAPK14 mediated cell survival in cells exposed to DNA damaging agents
  • driver of tumour cell invasion, an activity mediated by RhoA activation and cytoskeletal reorganisation
  • requires interaction with PDZ domain proteins, such as DLG1, to protect it from proteasome-mediated degradation and to maximally stimulate RHOA and that this interaction is regulated by cell-cell contact
  • guanine nucleotide exchange factor of RHOA, critical for TGF-beta1-induced cytoskeletal reorganization, N-cadherin expression, and RHOA activation
  • nuclear guanine nucleotide exchange factors ECT2 and NET1 regulate RHOB-mediated cell death after DNA damage
  • might potentially have a previously unidentified function in the nucleus of cells
  • functional NET1/RHOA signaling pathway within the nucleus of the cell and implicate them in the DNA damage response
  • required for chromosome congression during metaphase and generation of stable kinetochore microtubule attachments
  • is a novel regulator of mitosis, indicating that altered expression of NET1, as occurs in human cancers, may adversely affect genomic stability
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    SAPK/JNK pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with RHOA in its GTP- and GDP-bound states, and with CDC42 in its GTP-bound
  • state
  • interacts with the PDZ1 domain of BAIAP1
  • interaction between NET1 and DLG1 may contribute to the mechanism of NET1-mediated transformation
  • interacts with PDZ domain-containing proteins within the Discs Large (Dlg) family and relocalizes them to the nucleus
  • binds directly to the first two PDZ domains of DLG1 and both PDZ domains are required for maximal interaction in cells
  • direct gene target of TGF-beta1 via SMAD3
  • ability of NET1 to control mitosis is independent of RHOA or RHOB activation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS