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FLASH GENE
Symbol SKAP2 contributors: mct/npt - updated : 25-08-2015
HGNC name src kinase associated phosphoprotein 2
HGNC id 15687
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a coiled-coil domain at its N-terminus for self-dimerization
  • SH3 domain acting on cell migration, being the binding site for WASF2 suggesting that SKAP2 may interact with proline-rich proteins that coexist at the cell membrane and contribute to the reorganization of the actin cytoskeleton
  • a pleckstrin homology (PH) domain for interaction with lipids at the membrane
  • HOMOLOGY
    interspecies ortholog to murine Scap2
    intraspecies homolog to src family associated phosphoprotein 1
    Homologene
    FAMILY
  • src family kinases
  • SKAP family
  • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • highly expressed at the anterior tip of lens elongating fiber cells (Zhou 2010)
  • localized at actin-rich ruffles in lens epithelial cell (Zhou 2010)
  • basic FUNCTION
  • playing an essential role in the src signaling pathway in various cells
  • its expression in dendritic cells is required for the induction of an optimal immune response
  • essential role for HSF4-mediated SKAP2 expression in the regulation of actin reorganization during lens differentiation, likely through a mechanism that SKAP2 anchors the complex of NCK2/focal adhesion to FGF receptors at the lamellipodium in lens epithelial cells (Zhou 2010)
  • hematopoietic adaptor protein that is necessary for macrophage migration, chemotaxis, global actin reorganization and local actin reorganization upon integrin engagement
  • macrophages require SKAP2 and SIRPA for integrin-stimulated cytoskeletal rearrangement
  • is a negative regulator of actin assembly and tumor invasion
  • negatively regulates cell migration and tumor invasion in fibroblasts and glioblastoma cells by suppressing actin assembly induced by the WASF2-CTTN complex
  • plays an important role in the control of actin assembly and cell migration
  • novel role of SKAP2 and its phosphorylation in the regulation of cellular motility
  • integrin activation by the FYB-SKAP2-signaling module controls the stability and duration of T cell-dendritic cell contacts during the progressive phases necessary for optimal T cell activation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    src signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to Src family protein tyrosine kinases and SLAP/FYB (SLA)
  • downstream target of HSF4b and highly expressed at the anterior tip of lens elongating fiber cells (Zhou 2010)
  • interacted with the SH2 domain of non-catalytic region of tyrosine kinase adaptor protein 2 (NCK2) via its N-terminus
  • essential role for HSF4-mediated SKAP2 expression in the regulation of actin reorganization during lens differentiation, likely through a mechanism that SKAP2 anchors the complex of NCK2/focal adhesion to FGF receptors at the lamellipodium in lens epithelial cells
  • SKAP2 requires SIRPA for its recruitment to engaged integrins and for coordinating downstream actin rearrangement
  • suppresses actin polymerization and cell migration by inhibiting the interaction between WASF2 and CTTN
  • may be a unique Src family kinases (SFK) substrate that negatively regulates the invasiveness of certain types of tumor cells
  • suppresses potentially the translocation of WASF2 and causes changes in the cell membrane cytoskeleton
  • SKAP2 is a novel substrate of PTPN12
  • interaction of FYB with the adapter src kinase-associated phosphoprotein SKAP2
  • FAM102A is a new interactor of SKAP2
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    in pancreatic ductal adenocarcinoma (Harada 2008)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS