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FLASH GENE
Symbol WASF2 contributors: mct/ - updated : 09-09-2016
HGNC name WAS protein family, member 2
HGNC id 12733
Location 1p36.11      Physical location : 27.732.125 - 27.816.669
Synonym name
  • Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2
  • WASP family Verprolin-homologous protein 2
  • suppressor of cyclic-AMP receptor (WASP-family)
  • Synonym symbol(s) dJ393P12.2, WAVE2, SCAR2
    DNA
    TYPE functioning gene
    STRUCTURE 84.54 kb     9 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    HMGN2 1p36.1 high-mobility group nucleosomal binding domain 2 RPS6KA1 1p36-p35 ribosomal protein S6 kinase, 90kDa, polypeptide 1 SMARCF1 1p36.1-p35 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily f, member 1 FLJ20477 1p35.3 hypothetical protein FLJ20477 ZDHHC18 1p35.3 zinc finger, DHHC domain containing 18 SFN 1p35.3 stratifin FLJ10349 1p35.3 hypothetical protein FLJ10349 FLJ12455 1p35.3-p35.1 hypothetical protein FLJ12455 NR0B2 1p36.1 nuclear receptor subfamily 0, group B, member 2 NUDC 1p35-p34 nuclear distribution gene C homolog (A. nidulans) FLJ34633 1p35.3 hypothetical protein FLJ34633 LOC391022 1 similar to DC2 protein LOC388610 1 LOC388610 MGC16491 1p35.3 hypothetical protein MGC16491 SLC9A1 1p35 solute carrier family 9 (sodium/hydrogen exchanger), isoform 1 (antiporter, Na+/H+, amiloride sensitive) LOC391023 1 similar to ribosomal protein L18a; 60S ribosomal protein L18a LOC284609 1p35.3 similar to hypothetical protein FLJ20420 LOC148356 1p35.3 similar to nucleophosmin 1; nucleolar phosphoprotein B23; numatrin; nucleophosmin/nucleoplasmin family, member 1 WDTC1 1p35.3 WD and tetratricopeptide repeats 1 DKFZP564D0478 1p35.3 hypothetical protein DKFZp564D0478 JFC1 1p35.3 hypothetical protein DKFZp564D0478 MAP3K6 1p35.2 mitogen-activated protein kinase kinase kinase 6 FCN3 1p36-p32 ficolin (collagen/fibrinogen domain containing) 3 (Hakata antigen) LOC388611 1 similar to EAPG6122 GPR3 1p35.1-p34.3 G protein-coupled receptor 3 WASF2 1p36.11-p34.3 WAS protein family, member 2 DJ159A19.3 1p36.13 hypothetical protein DJ159A19.3 LOC388612 1 LOC388612 FGR 1p35 Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog G1P3 1p35 interferon, alpha-inducible protein (clone IFI-6-16) LOC339409 1p35.3 similar to Procollagen (type III) N-endopeptidase MGC34648 1p35.3 hypothetical protein MGC34648 STX12 1p35-p34.1 syntaxin 12 PPP1R8 1p35 protein phosphatase 1, regulatory (inhibitor) subunit 8 C1orf38 1p35.2 chromosome 1 open reading frame 38 RPA2 1p35 replication protein A2, 32kDa ASML3B 1p35.2 acid sphingomyelinase-like phosphodiesterase FLJ10307 1p35.2 hypothetical protein FLJ10307 EYA3 1p36 eyes absent homolog 3 (Drosophila) LOC388613 1 similar to Microsomal signal peptidase 25 kDa subunit (SPase 25 kDa subunit) (SPC25) LOC391024 1 similar to RIKEN cDNA 2610313E07 PTAFR 1p35.1-p34.3 platelet-activating factor receptor DNAJC8 1p35.3 DnaJ (Hsp40) homolog, subfamily C, member 8 ATPIF1 1p35.3 ATPase inhibitory factor 1 SESN2 1p35.3 sestrin 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 4270 - 498 - 2009 19917258
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   moderately
     pharynx   moderately
    Lymphoid/Immunetonsils   moderately
    Nervousnervecranial nerve  highly
    Reproductivefemale systemuteruscervix highly
    Respiratorylung    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion moderately in lymph
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text placenta, vascular endothelial cells, predominantly in umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • a N terminal leucine-zipper and a highly basic region
  • three MAP kinase phosphorylation sites
  • a proline-rich domain that regulates actin assembly at the cell membrane
  • a C terminal VPH (verproline homology)/WH2 (WASP homology 2) domain, verprolin central acidic (VCA) domain, responsible for binding to and activating the Arp2/3 complex, which in-turn nucleates the formation of new actin filaments
  • HOMOLOGY
    Homologene
    FAMILY
  • SCAR/WAVE family
  • CATEGORY regulatory , structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microfilament
    text
  • actin cytoskeleton
  • at the interface between the lamellipodial actin meshwork and the membrane
  • PRKACA is localized at the leading edge of membrane protrusions and colocalized with WASF2
  • MAPK1 colocalizes with the WASF2 regulatory complex (WRC) at lamellipodial leading edges and directly phosphorylates two WRC components: WASF2 and ABI1
  • DIAPH1 and WASF2 synergize with BAIAP2 to form filopodia
  • might be retained in the cytoplasm through its association with SKAP2
  • basic FUNCTION
  • acting as a potential regulator of actin cytoskeleton and playing a key role in the induction of actin-based processes
  • required for directed cell migration, angiogenesis and cardiovascular development
  • playing a critical role in actin-based processes downstream of Rac that are essential for cell movement
  • implicated in cancer metastasis
  • implicated in the formation of peripheral ruffles and chemotactic migration
  • with DOCK3, NEDD9, ARHGAP22, are key molecules regulating RAC1 and RHO signaling that determine the mode of movement driving melanoma cell metastasis
  • membrane transport of WASF2 implicated in formation of lamellipodia, the first step during cell migration, and involves actin reassembly
  • involved in lamellipodia formation necessary for epithelial cell migration and invasion
  • regulates membrane protrusions and cell migration by promoting Arp2/3 complex-dependent actin reorganization
  • WASF2 and WASL have parallel pathways to F-actin reorganization and function in human NK cells
  • critical role for WASF2 complex in regulation of cellular signaling and epithelial morphogenesis
  • mediates actin cytoskeletal reorganization and lamellipodia protrusion formation, which are required for cell migration and invasion
  • WAS and WASF2 differ in their dynamics and their associated proteins
  • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    text
  • cell shape control
  • PATHWAY
    metabolism
    signaling signal transduction
    downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton
    a component
  • associating with the Arp2/3 complex a nucleating core constituent for actin polymerization in vitro
  • complex ABL1/ABI1/WASF2 as critical pathway for coupling stimulatory signals to actin cytoskeletal remodeling
  • WAVE complex can integrate coincident signals to promote localized actin nucleation during cell motility
  • WASF2-PRKACA complex is potentially localized at membrane protrusions
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
  • DIAPH1 and WASF2 are important SH3 domain partners of BAIAP2 involved in filopodial protrusion
  • effect of EXOC7 on actin is mediated by promoting the interaction of the Arp2/3 complex with WASF2, a member of the N-WASP/WAVE family of nucleation promoting factors
  • SKAP2 suppresses actin polymerization and cell migration by inhibiting the interaction between WASF2 and CTTN
  • SKAP2 suppresses potentially the translocation of WASF2 and causes changes in the cell membrane cytoskeleton
  • WASF2 complex regulates breast epithelial morphology by a complex mechanism involving repression of TWIST1 expression and ABL kinase activity
  • CTTN can directly bind WASF2, as well as Arp2/3, and both these interactions are necessary for actin assembly at the zonula adherens (ZA)
  • SH3BP1 specifically inactivating RAC1 and its target WASF2 is required for cell motility, thus regarded as an essential regulator of cancer cell metastasis
  • cell & other
    REGULATION
    activated by ABL1 via tyrosine phosphorylation (to promote actin remodeling ABL1 forms the crucial link between these two factors)
    phosphorylation (activation of the WASF2 complex requires simultaneous interactions with prenylated Rac-GTP and acidic phospholipids, as well as a specific state of phosphorylation)
    Other phosphorylation of WASF2 by MAP kinases regulates cell polarity during migration
    ARHGEF7 and GIT1 regulate HGF-induced lamellipodia formation and WASF2 transport
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    the chromosome region frequently undergoes loss of heterozygosity in advanced stage of neuroblastoma
    tumoral   deletion    
    the chromosome region frequently undergoes deletion in advanced stage of neuroblastoma
    tumoral     --over  
    in node-positive cases as well as in moderately and poorly differentiated breast tumours
    constitutional     --low  
    excessive oxidative stress can decrease WASF2 expression in trophoblasts and the decreased expression of WASF2 in trophoblast cells may be involved in the development of pre-eclampsia
    Susceptibility
    Variant & Polymorphism
    Candidate gene for a candidate prognostic marker of hepatocellular carcinoma (HCC)
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Wave2 deficient mice generated by a targeted gene disruption