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FLASH GENE
Symbol WASL contributors: npt/mct/pgu - updated : 19-08-2010
HGNC name Wiskott-Aldrich syndrome-like
HGNC id 12735
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a pleckstrin homology domain (PH)
  • an IQ motif,a PBD/CRIB motif
  • a proline-rich region
  • a WASP homology region (WH1) region
  • a Cterminal VCA region (a verprolin homology, cofilin homology and acidic region)inducing actin polymerization
    • HOMOLOGY
    intraspecies homolog to WASP
    Homologene
    FAMILY
    CATEGORY regulatory , structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microfilament
    intracellular,nucleus
    text
  • actin-cytoskeleton associated
  • localized to the Z bands in mature skeletal muscle and became confined to the Z bands during muscle regeneration
  • recruited to the Z bands through the binding to nebulin
    • basic FUNCTION
  • inducing long actin microspikes when coexpressed with active CDC42
  • activating the ARPCs complex, for the actin polymerization
  • playing a critical role for the formation of large integrin structures and assembly of vinculin patches and in cell adhesion to fibronectin
  • regulates the formation of dendritic spines and synapses in hippocampal neurons
  • critical role for WASL and the Arp2/3 complex in spine and synapse formation
  • activator of actin nucleation through the Arp2/3 complex
  • actin nucleation regulator and a novel element of hair-cycle control that modulates the antiproliferative and pro-apoptotic TGFbeta pathway in keratinocytes
  • required for IGF1–induced muscle hypertrophy
  • involved in the regulation of actin filament nucleation in Schwann cells, which is crucial for membrane wrapping, longitudinal extension, and myelination
  • WASF2 and WASL have parallel pathways to F-actin reorganization and function in human NK cells
  • WIPF3 and WASL play likely a role in the pathogenesis of azoospermia
  • major cytoskeletal regulator that stimulates Arp2/3-mediated actin nucleation
  • a junctional protein whose depletion decreased junctional F-actin content and organization
  • is crucial for extension of invasive pseudopods into which MMP14 traffics and for providing the correct cytoskeletal framework to couple matrix remodeling with protrusive invasion
  • WASL-mediated actin nucleation of branched microfilament networks is likely specifically required for the maintenance of podocyte foot processes, presumably sustaining the mechanical resistance of the filtration barrier
  • is required for structural integrity of the blood-testis barrier
  • regulates endothelial monolayer integrity by affecting the organization of cell junctions
  • novel role for WASL in remodeling EC junctions, which is critical for monolayer integrity and function
  • CDC42/WASL/stress fibers/YAP1 signal pathway may potentially play an important role in regulating podocyte apoptosis
  • positively regulates demarcation membrane system (DMS) development and proplatelet formation (PPF), and the Src family kinases in association with CDC42 regulate PPF through WASL
    • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    text
  • filopodium formation
  • actin polymerization
    • PATHWAY
    metabolism
    signaling signal transduction
    a component
  • associating with the cytoskeletal organizing complex Arp2/3(ARPCs)
  • part of FNBP1L-WASL complex (this complex can link filopodial formation to endocytosis)
  • nebulin–WASL complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex *
  • ABI1 and the neural WASL, forms a complex with KCNN3- channels in neural stem cells, involved in early neurogenesis
  • WASL/WIPF2 serves as an integrator that couples actin nucleation with the subsequent steps of filament stabilization and organization necessary for zonula adherens integrity
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NICKIPSD-interacting protein that binds and activates WASL to recruit the Arp2/3 complex in a Cdc42-independent manner
  • actin
  • ARP2/3(activated by the VCA region)
  • WIRE
  • synergize with CTTN for ARCTs-dependent actin polymerization
  • interacting with WAS (T cell development depends on the combined activity of WAS and WASL)
  • interact with the verprolin family of proteins, WIPF1, WIPF2, and WIPF3
  • interaction with FNBP1L (both require each other to induce filopodia)
  • interaction between GAS7 and WASL is mediated by WW-Pro domains, which is unique in the PCH protein family, where most interactions are of the SH3-Pro kind
  • by mediating intensive F-actin accumulation at the sites of cell infiltration, WASF2, WASL, and ENAH are crucial for PI3K-dependent cell invasion induced by PDGFA
  • in actively invading cells, WASL promoted trafficking of MMP14 into invasive pseudopodia, primarily from late endosomes, from which it was delivered to the plasma membrane
  • WIPF1 acts as an essential link between NCK1 and WASL
  • ITSN1 is an important general regulator of CDC42-, NCK1- and WASL-dependent actin polymerisation
  • CTTN is a key scaffold for actin regulation at the zonula adherens (ZA), which localizes to the ZA through influences from both CDH1 and WASL
  • N-terminus of BCAR1 associates with the PTK2-WASL complex at the protrusive edge of the cell and the C-terminus of BCAR1 associates with the immobilized integrin-Src family kinases (SFKs) cluster
  • role for WASL in BIN1-dependent nuclear positioning and triad organization and in centronuclear myopathy (CNM) and myotonic dystrophy pathophysiology
  • NCK1 was the most potent activator of WASL-driven actin assembly
  • GRB2 N-terminal and C-terminal SH3 domains bind to proline rich proteins such as WASL
    • cell & other
    REGULATION
    Other insertion of I30 region in WASL (WASL-I30) enabled WASL to rescue the chemotactic defect of Jurkat(WKD) T-cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    deficiency leads to reduced adhesion to fibronectin and increased cell motility
    tumoral   LOH    
    in breast cancer
    constitutional     --low  
    in men with idiopathic azoospermia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    is an important potential therapeutic target in lung cancer invasion
    ANIMAL & CELL MODELS