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FLASH GENE
Symbol DAB2IP contributors: mct/pgu - updated : 13-02-2010
HGNC name DAB2 interacting protein
HGNC id 17294
Location 9q33.2      Physical location : 124.329.398 - 124.547.807
Synonym name
  • DOC-2/DAB2 interactive protein
  • nGAP-like protein
  • ASK-interacting protein
  • disabled homolog 2 interacting protein
  • Synonym symbol(s) AF9Q34, KIAA1743, DIP1/2, AIP1, FLJ39072
    DNA
    TYPE functioning gene
    STRUCTURE 218.41 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure binding for Sp1, AP-2, AP-3, E4TF1, ISRE
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 5472 - 1132 - 2009 PMID: 199038
    17 exons
    14 - 3500 - 1065 - 2009 PMID: 199038
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvesselaorta  highly Homo sapiens
    Endocrinethyroid   highly
    Nervousbrain   highly Homo sapiensAdult
    Reproductivefemale systemplacenta  highly
     female systemovary  highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmoothvessel highly Homo sapiens
    Muscularstriatumcardiac highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Reproductiveepithelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminus containing the C2 and GAP domains constitutively binds to MAP3K5 and facilitating the release of 14-3-3 from MAP3K5
  • one PH domain and one FLR motif
  • a proline-rich region (amino acids 796-807) critical for maintaining DAB2IP in a closed form, which associates with a region of TNFR1 distinct from the death domain, the site of TNFR1 association with TRADD
  • C terminal leucine zipper domain
  • HOMOLOGY
    interspecies homolog to rattus Dip1/2
    intraspecies homolog to RASA1
    Homologene
    FAMILY
  • RAS GTPase activating protein family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,nucleus
    basic FUNCTION
  • mediating TNF-alpha-induced ASK1 activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5, a novel mechanism by which TNF-alpha activates MAP3K5
  • transducer in TNF-induced TRAF2-dependent activation of MAP3K5 that mediates a balance between JNK versus NF-kappaB signaling
  • being essential for transducing the IRE1-mediated ER stress response
  • potent growth inhibitor by inducing G0/G1 cell cycle arrest and is proapoptotic in response to stress
  • can coordinate PI3K-Akt inactivation with ASK1 activation pathways
  • unique scaffold protein to balance pathways of cell proliferation, survival, and death
  • functions as a scaffold protein in regulating epithelial-to-mesenchymal transition by modulating nuclear beta-catenin/T-cell factor activity
  • ; suppress cell survival and proliferation through suppression of the PI3K-Act and RAS pathways and to induce apoptosis through activation of MAP3K5, a member of the JNK and MAPK14 pathways
  • endogenous inhibitor of KDR-mediated signaling, an important regulator of angiogenesis control (
  • GTPase activating protein that binds to Disabled-1, a cytosolic adapter protein involved in Reelin signaling and brain development
  • plays an important role in dendrite development and regulates the number of synapses in the cerebellum
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DAB2
  • MAP3K5
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in prostate cancer
    tumoral fusion translocation    
    fused with MLL in t(9;11) (q34;q23) in acute myeloid leukemia
    tumoral        
    leads to imbalance of cell survival and apoptosis pathways, which plays a significant role in tumor development
    Susceptibility
  • to aggressive prostate cancer
  • to early onset myocardial infarction, peripheral arterial disease, abdominal aortic aneurysms and pulmonary embolism
  • Variant & Polymorphism SNP
  • in the DAB2IP gene is associated with risk of aggressive prostate cancer (PCa), and loss of DAB2IP expression is frequently detected in metastatic PCa
  • rs7025486[A] is associated with early onset myocardial infarction, peripheral arterial disease, abdominal aortic aneurysms and pulmonary embolism
  • Candidate gene
    Marker assessment of DAB2IP may provide a prognostic biomarker in prostate carcinoma metastasis
    Therapy target
    SystemTypeDisorderPubmed
    cancermetastases 
    potential therapeutic target for Prostate Carcinoma metastasis
    ANIMAL & CELL MODELS
  • AIP1-deficient mice (AIP1-KO)
  • Dab2IP knock-down mice did not exhibit severe ataxia or cerebellar hypoplasia, but Dab2IP deficiency produced a number of cerebellar abnormalities such as a delay in the development of Purkinje cell (PC) dendrites