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FLASH GENE
Symbol WIPF1 contributors: mct/npt - updated : 13-06-2015
HGNC name WAS/WASL interacting protein family, member 1
HGNC id 12736
Corresponding disease
WASP2 Wiskott-Aldrich syndrome 2
Location 2q31.1      Physical location : 175.424.302 - 175.547.627
Synonym name
  • WASP-interacting protein
  • Wiskott-Aldrich syndrome protein interacting protein
  • protein PRPL-2
  • Synonym symbol(s) WIP, PRPL-2, MGC111041, WASPIP
    DNA
    TYPE functioning gene
    STRUCTURE 123.32 kb     8 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 4600 - 503 - Dong (2007)
    8 - 4664 - 503 - Dong (2007)
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     spleen   highly
     thymus   highly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminus is a highly inhibitory region for TCR-mediated transcriptional activation in which at least two elements contribute: the N-terminal polyproline and the N-terminal actin-binding WH2 domain, playing a role in filament nucleation by Arp2/3 complex, and interaction with actin is mediated by a pair of conserved actin binding motifs (ABMs) at the WIP N-terminus
  • HOMOLOGY
    Homologene
    FAMILY
  • verprolin family
  • CATEGORY immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • co-localization of ITSN1 and WIPF1 at sites of invadopodia formation and in clathrin-coated pits
  • basic FUNCTION
  • may have direct activity on the actin cytoskeleton and inducing actin polymerization and redistribution
  • playing an important role in the intracellular motility
  • of vaccinia virus by functioning as an adapter for recruiting WASL to vaccinia virus
  • stabilizes WAS and may also be important for its function
  • essential for IL2 signaling and responsiveness in T cells, possibly because of its critical role in TCR-triggered actin cytoskeletal reorganization (le Bras 2009)
  • plays, independently of WAS, a critical role in T cell activation by antigen, IL2 signaling and responsiveness, and cytoskeletal rearrangement (Le Bras 2009)
  • actin-binding protein involved in the regulation of actin polymerization in cells, such as fibroblasts and lymphocytes
  • is a previously unreported regulator of neuronal maturation and synaptic activity
  • WAS and WIPF1 localise to the actin rich core of podosomes and play a critical role in their formation
  • involvement in the control of migratory persistence in both mesenchymal (fibroblast) and amoeboid (B lymphocytes) motility
  • is a novel regulator of focal adhesion (FA) assembly and cell adhesion
  • key role in actin polymerization in activated T cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • WIP-WASP complex playing an important role in WASP stabilization and NFAT activation
  • complex formation of FNBP1 with WAS, WIPF1, and dynamin-2 at the plasma membrane is critical for the formation of podosomes and phagocytic cups (Tsuboi 2009)
  • WIPF1/ITSN1 complex is involved in the cellular vesicle trafficking and actin-dependent membrane processes
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • stabilizes WAS and it may also be important for its function
  • role for DBNL in growth factor-induced dorsal ruffle formation through its interaction with WIPF1
  • WIPF1 acts as an essential link between NCK1 and WASL
  • binds to and stabilizes WAS and also interacts with actin, and WIPF1 interaction with actin may be important for T cell cytoskeletal integrity and function
  • WIPF1 interacts with endocytic adaptor proteins of the intersectin (ITSN) family, ITSN1 and ITSN2
  • WIPF1 interaction with ITSN1 highly implicated in endo-/exocytosis, apoptosis, mitogenic signaling and cytoskeleton rearrangements
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) WASP2
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyimmunodeficiency 
    A WAS-binding WIPF1-derived peptide stabilizes WAS in cells from XLT patients with missense mutations that disrupt WIPF1 binding, and corrects their T-cell actin cytoskeleton defect
    immunologyinflammatory 
    disruption of WIPF1 binding to actin could be of therapeutic value in T cell-driven inflammatory diseases.
    ANIMAL & CELL MODELS
  • Wip(-/-) murine hippocampal neurons exhibit enlargement of somas as well as overgrowth of neuritic and dendritic branches that are more evident in early developmental stages