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FLASH GENE
Symbol VANGL2 contributors: mct/pgu - updated : 03-04-2015
HGNC name vang-like 2 (van gogh, Drosophila)
HGNC id 15511
Location 1q23.2      Physical location : 160.370.363 - 160.398.467
Synonym name
  • strabismus 1
  • loop-tail mouse homolog, Drosophila strabismus homolog
  • vang-like protein 2
  • van, van gogh-like 2
  • loop tail protein 1 homolog
  • loop tail associated protein
    • Synonym symbol(s) KIAA1215, LTAP, LPP1, STB1, MGC5338, STBM, STBM1, MGC119403, MGC119404
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text STB1/CASQ1 gene cluster
    STRUCTURE 28.10 kb     8 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map qter - D1S2170 - D1S484 - LY9 - CD48 - SETDB1 - SLAMF1 - D1S2771 - [CD84 - VANGL2 - NHLH1 - NCSTN - COPA - PEX19 - PEA15 - CASQ1 - ATP1A4 - ATP1A2 - KCNJ9 - KCNJ10 - IGSF9 ] - TAGLN2 - CCDC19 - CRP - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 5415 - 521 - 1999 10574462
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Cardiovascularheart    
    Endocrinepancreas    
    Hearing/Equilibriumearinnercochlea  
    Nervousbrainhindbrainmedulla oblongata  
     braindiencephalonamygdala  
     brainhindbraincerebellum  
    Reproductivefemale systemovary   
     male systemprostate  highly
     male systemtestis   
    Respiratorylung    
     respiratory tracttrachea  highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text neuroectoderm throughout early neurogenesis, fetalbrain and liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four transmembrane domains with Dishevelled-binding motif
  • a PDZ-domain binding motif at the Cterminus
    • HOMOLOGY
    interspecies homolog to Drosophila strabismus/van Gogh
    homolog to murine Vangl2 (99.4pc)
    homolog to rattus Vangl2 (99.4pc)
    intraspecies homolog to VANGL1
    Homologene
    FAMILY
  • Vang family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • localizes to the basal body and axoneme of ciliated cells
  • integral membrane proteins that assemble into asymmetrically distributed membrane complexes that establish planar cell polarity in epithelial cells and that regulate convergent extension movements during embryogenesis
  • localization of the VANGL2 protein to specific intracellular microdomains is crucial for its function
    • basic FUNCTION
  • planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an peithelial sheet or multicellular clusters, which polarize as a group
  • involved in the control of early morphogenesis and patterning of both axial midlines structures and the development of neural plate
  • plays a role in the regulation of planar cell polarity, particularly in the orientation of stereociliary bundles in the cochlea
  • role for VANGL2 in the targeting or anchoring of FZD3, suggesting that novel Planar cell polarity mechanisms exist in vertebrates
  • required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process
  • regulates tumor cell migration and matrix metalloproteinase-dependent invasion
  • activating the WNT/JNK pathway and inhibiting the WNT/beta catenin pathway
  • required for lung epithelial tube formation
  • is one of the central proteins controlling the establishment of planar cell polarity in multiple tissues of different species
  • CFL1 and VANGL2 cooperate likely in the initiation of planar cell polarity in the embryo
  • play a critical role in establishing planar cell polarity (PCP) in epithelial cells and are required for convergent extension (CE) movements during embryogenesis
  • VANGL1 and VANGL2 are essential for embryonic development, cell adhesion, migration and polarity
    • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    text neurogenesis, neural tube development
    PATHWAY
    metabolism
    signaling signal transduction
  • Drosophila strabismus/van Gogh is a component of the frizzled/dishevelled tissue polarity pathway
  • planar cell polarity signaling pathway
  • potentially part of the WNT5A/PCP/PRICKLE1 signaling, regulating cell polarity and affecting expression of multiple factors to stunt limb growth through altered patterns of gene expression, including the PCP genes WNT5a and VANGL2
    • a component
  • RYK and VANGL2 proteins form a complex, whereas RYK also activated RHOA, a downstream effector of PCP(Planar Cell Polarity) signaling
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with BBS1, BBS2, ARL6, BBS4, MKKS, BBS7, BBS5, TTC8
  • interacting with DVL1, DVL2, DVL3, MAGI3, SCRIB/SCRIB1 and FZD3
  • homotypic intracellular interactions of CELSR1 are required to recruit VANGL2 and FZD6 to sites of cell-cell contact
  • GNB2L1 is an interacting protein of VANGL2 (interact with GNB2L1 to regulate adherens junctions during PCP signaling in vertebrates)
  • VANGL2 promotes Wnt/planar cell polarity-like signaling by antagonizing DVL1-mediated feedback inhibition in growth cone guidance
  • link between MINK1 and the VANGL2-PRICKLE1 complex and importance of PRICKLE1 phosphorylation and endosomal trafficking for its function during WNT-PCP signaling
  • RYK is required for Wnt/planar cell polarity signaling during mammalian development and signals via VANGL2 and RHOA
  • GIPC1 is a new interactor for VANGL2, and MYO6-GIPC1 protein complex can regulate VANGL2 traffic in heterologous cells
  • genetic interactions between FZD2, FZD7 and VANGL2, DVL3 and WNT genes reflect interactions among different signaling pathways in developmental processes that are highly sensitive to perturbations in Frizzled signaling
  • ARFRP1, and the clathrin adaptor complex 1 (JUN) are required for VANGL2 transport from the trans Golgi network (TGN)
  • VANGL2 forms a complex with DLG4 through direct binding (C-terminal PDZ-binding motif of VANGL2 is required for localization to dendritic spines)
  • SDC4 interacts genetically with VANGL2 to regulate neural tube closure and planar cell polarity
  • direct interactions of TTC8 and IFT20 with VANGL2
  • SDC4 controls flow-induced lymphatic endothelial cells (LECs)
    • polarization via regulation of VANGL2 expression
    cell & other
    REGULATION
    Other regulated by DACT1 upstream of cell adhesion and the planar cell polarity pathway
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in primary kidney cancer
    constitutional germinal mutation      
    in sporadic or familial cases of neural tube defects
    Susceptibility to isolated neural tube defects (NTDs)
    Variant & Polymorphism other
  • missense mutations were identified in patients affected with closed spinal NTDs
    • Candidate gene loss of function mutation of VANGL2 show that it has an essential role in hair follicle polarization and orientation
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    in zebrafish embryos, VANGL2 is required for asymmetric localization of cilia to the posterior apical membrane of neuroepithelial cells