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FLASH GENE
Symbol WWP1 contributors: mct/npt/pgu - updated : 10-04-2017
HGNC name WW domain containing E3 ubiquitin protein ligase 1
HGNC id 17004
Location 8q21.3      Physical location : 87.354.993 - 87.480.176
Synonym name
  • WW domain-containing protein 1
  • atrophin-1 interacting protein 5
  • Nedd-4-like ubiquitin-protein ligase
  • TGIF-interacting ubiquitin ligase 1
  • Synonym symbol(s) AIP5, Tiul1, hSDRP1, DKFZP434D2111
    EC.number 6.3.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 125.18 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 4120 - 922 - 2002 11779188
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Hearing/Equilibriumearinnercochlea highly
    Reproductivefemale systembreastmammary gland highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • at the N terminus, a proline-rich domain and a polyserine motif with an adjacent C2 domain
  • four tandem WW domains for substrate binding
  • two highly conserved tryptophans
  • a partial HECT (homologous to the E6-associated protein carboxyl terminus) domain
  • PPXY motif, not required for spartin ubiquitination
  • a C-terminal catalytic HECT domain for ubiquitin transferring
  • HOMOLOGY
    interspecies homolog to murine Wwp1
    Homologene
    FAMILY
  • NEDD4-like protein family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • ubiquitin protein ligase, regulating key trafficking decisions, including targeting of proteins to proteasomes or lysosomes
  • upregulates and maintains erythroblastic leukemia viral oncogene homolog 2 (ERBB2) and epithelial growth factor receptor (EGFR) in multiple cell lines
  • may promote cell proliferation and survival partially through suppressing RNF11-mediated ERBB2 and EGFR downregulation
  • suppressing ERBB4 expression and function in breast cancer
  • may play an important role in ER positive breast cancer
  • may have a context-dependent role in regulating cell survival through targeting different TP63 proteins for degradation
  • markedly inhibited the replicative senescence induced by CDKN1B by promoting CDKN1B degradation
  • may promote human fibroblast proliferation by stimulating cell cycle progression
  • promotes CDKN1B degradation through the ubiquitin-proteasome pathway, and plays an important role in the regulation of cellular senescence
  • function as the E3 ligase for several PY motif-containing proteins
  • appears to be involved in insulin resistance through suppressing PRKAA2 expression
  • acting as an E3 ubiquitin ligase in TLR-mediated inflammation
  • important negative regulator of TLR4-mediated TNF and Il6 production
  • participates in a wide variety of biological processes and is tightly related to the initiation and progression of many tumors
  • acts as an oncogenic factor and should be considered as a novel interfering molecular target for gastric carcinoma
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • WWP1 forms a protein complex with RNF11
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ZCCHC14
  • interacting with KLF5 (WWP1 mediated the ubiquitination and degradation of KLF5, through the catalytic cysteine residue)
  • interaction with RNF11 through the first and third WW domains of WWP1 and the PY motif of RNF11
  • interacting partner for RTN4 (interaction which may regulate the RTN4 level by controlling its ubiquitination)
  • targets KLF5 for ubiquitin-mediated degradation
  • regulates deltaNp63 (TP63) transcriptional activity, acting thus as a potential regulator of the proliferation and survival of epithelial-derived cells
  • decreases CDKN1B protein levels and CDKN1B may play a key regulatory role in WWP1-mediated cellular senescence
  • EZR ubiquitylation by WWP1 in epithelial cells leads to the upregulation of MET level in absence of HGF stimulation and increases the response of MET to HGF stimulation as measured by the ability of the cells to heal a wound
  • down-regulated PRKAA2 under high glucose culture conditions via the ubiquitin-proteasome pathway
  • is essential for LATS1 stability and negatively regulate LATS1 by promoting LATS1 degradation through polyubiquitination and the 26S proteasome pathway
  • WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway
  • functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination
  • phosphatase PPM1G is a functional switch that controls the balance between monomeric WWP2 and a WWP2/WWP1 heterodimeric state in the cell
  • BAP1 antagonized WWP1-mediated ubiquitination of KLF5 to inhibit autophagy and promote melanoma development
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in some cancer cell lines from the prostate and breast
    tumoral     --over  
    associated with the estrogen receptor and insulin-like growth factor receptor 1 in breast carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    promising therapeutic strategy in which developed drugs targeting WWP1 cause activation of LATS1 in suppressing breast cancer cell growth
    ANIMAL & CELL MODELS