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FLASH GENE
Symbol WWTR1 contributors: mct/npt/pgu - updated : 23-02-2016
HGNC name WW domain containing transcription regulator 1
HGNC id 24042
Location 3q25.1      Physical location : 149.235.021 - 149.421.060
Synonym name transcriptional co-activator with PDZ-binding motif (TAZ)
Synonym symbol(s) DKFZp586I1419, TAZ
DNA
TYPE functioning gene
STRUCTURE 186.04 kb     7 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
7 - 5135 - 400 - 2008 18568018
8 - 5052 - 400 - 2008 18568018
7 - 4999 - 400 - 2008 18568018
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systemuterus    Homo sapiensAdult
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier liningendometrium   Homo sapiensAdult
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a PDZ-binding motif
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • enhancing GLIS3-mediated transcriptional activation, indicating that WWTR1 functions as a coactivator of GLIS3
  • functioning as a modulator of several transcription factors
  • 14-3-3 binding protein, which modulates mesenchymal stem cell differentiation and plays a critical role in the migration, invasion, and tumorigenesis of breast cancer cells
  • transcription coactivator that modulates mesenchymal differentiation and development of multiple organs
  • potential function as an important target of the Hippo pathway in regulating cell proliferation tumorigenesis
  • functions as a novel transcriptional modulator of myogenic differentiation by promoting MYOD1-mediated myogenic gene expression
  • transcriptional coactivator involved in the differentiation of stem cell as well as the development of multiple organs
  • oncogene and has an important role in tumorigenicity of non-small cell lung cancer cells
  • fundamental role of the transcriptional regulators YAP1 and WWTR1 as downstream elements in how cells perceive their physical microenvironment
  • promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation and enhancing KLF5 activities
  • its activity is associated with tumor differentiation and prognosis
  • required for self-renewal and tumor initiation of breast cancer cells
  • regulates mesenchymal differentiation in malignant glioma
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • component of the novel Hippo-LATS tumor suppressor pathway
  • downstream effector of the Hippo pathway
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with and functions as a coactivator of GLIS3 (GLIS3 and WWTR1 are part of overlapping transcription regulatory networks that play a critical role in the maintenance of normal renal architecture and function)
  • physically interacts with MYOD1 through the WW domain and activates MYOD1-dependent gene transcription
  • overexpression of AMOT and AMOTL1 caused cytoplasmic retention of WWTR1 and suppressed its transcriptional outcome such as the expression of CTGF and CYR61
  • YAP1/WWTR1 interaction are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry
  • NEK1 phosphorylates WWTR1 at a site essential for the ubiquitination and proteasomal degradation of PKD2
  • in epithelial cancer cells, SCRIB is an upstream activator of the Hippo pathway leading to WWTR1 inhibition
  • modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation
  • BMP4 is a mediator of WWTR1-induced cell migration (WWTR1induces BMP4 transcription through the TEAD family of transcription factors, which mediate BMP4 promoter activation through binding to TEAD response element 1)
  • ARHGEF7 is a key component that links the Hippo kinase cassette to YAP1/WWTR1 in response to multiple upstream Hippo pathway activators
  • actin remodelling factors LIMK2 and TESK1 are key players in the ciliogenesis control network in which YAP1/WWTR1 and directional vesicle trafficking are integral components
  • cell & other
    REGULATION
    Phosphorylated by NEK1
    Other phosphorylated by LATS1 tumor suppressor kinase, a key component of the Hippo pathway, whose alterations result in organ and tissue hypertrophy
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in approximately 20 p100 of breast cancer samples
    constitutional     --over  
    in placentas of preeclampsia and HELLP syndrome
    tumoral fusion      
    WWTR1-CAMTA1 fusion in all epithelioid hemangioendothelioma tested from bone, soft tissue, and visceral location (liver, lung) in keeping with a unique and specific pathological entity
    tumoral     --over  
    in non-small cell lung cancer (NSCLC)
    tumoral     --over  
    in high-grade breast cancers
    constitutional     --low  
    during decidualization
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    may present a novel target for the future diagnosis, prognosis and therapy of lung cancer
    ANIMAL & CELL MODELS