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FLASH GENE
Symbol CRB3 contributors: mct - updated : 26-03-2019
HGNC name crumbs cell polarity complex component 3
HGNC id 20237
Location 19p13.3      Physical location : 6.464.259 - 6.467.228
Synonym name
  • crumbs homolog 3 (Drosophila)
  • Synonym symbol(s) MGC17303, CRUMBS3, UNQ588/PRO1158
    DNA
    TYPE like-sequence
    STRUCTURE 2.97 kb     5 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
    4 splicing 1453 - 120 - 2016 26975581
  • CRB3A
  • CRB3A containing vesicles are slightly more immobile than CRB3B ones
  • different intracellular mobility patterns for CRB3A and CRB3B
  • 4 splicing 1118 - 120 - 2016 26975581
  • CRB3A
  • CRB3A containing vesicles are slightly more immobile than CRB3B ones
  • different intracellular mobility patterns for CRB3A and CRB3B
  • 5 - 777 - 123 - 2016 26975581
  • CRB3B
  • novel C-terminal sequence ending in CLPI (CRB3-CLPI)
  • CRB3-CLPI localizes to the cilia membrane and a membrane compartment at the mitotic spindle poles
  • different intracellular mobility patterns for CRB3A and CRB3B
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     stomach    
    Endocrinepancreas    
    Lymphoid/Immunespleen    
    Reproductivemale systemtestis    Homo sapiens
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegerm cell Homo sapiens
    ReproductiveSertoli cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • conserved cytoplasmic domain with other Crumbs but exhibiting a very short extracellular domain without the EGF- and laminin A-like G repeats present in the other Crumbs, including a conserved N glycosylation site
  • a transmembrane domain
  • a carboxy terminal PDZ domain
  • HOMOLOGY
    interspecies homolog to Drosophila Crumbs1
    intraspecies homolog to CRB1
    Homologene
    FAMILY Crumbs protein family
    CATEGORY structural protein , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    basic FUNCTION
  • playing a role in apical membrane morphogenesis and tight junction regulation
  • plays potentially an important role in epithelial tight junction formation
  • potential expanded role for Crumbs proteins in polarized membrane targeting and cell division via unique interactions with importin proteins
  • seems to be involved in regulating the establishment and stability of tight junctions and in ciliogenesis
  • is crucial for epithelial morphogenesis and plays a role in linking the apical membrane to the underlying ezrin-containing cytoskeleton
  • is required for airway differentiation by controlling the localization of the transcriptional regulator YAP1
  • is an actin microfilament regulator, playing a pivotal role in organizing actin filament bundles at the ES (ectoplasmic specialization)
  • CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions
  • regulates contact inhibition by activating the Hippo pathway in mammary epithelial cells
  • role for CRB3 in regulating proliferation in mammalian cells that is associated with changes in the endocytic trafficking machinery
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text cell polarity
    PATHWAY
    metabolism
    signaling
    cell cell signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with PARD6A
  • CRB3 and the RAC1-PI3K module are antagonists, and the fine balance between the activities of these proteins is crucial to maintain epithelial organization and an appropriate apical to basolateral ratio
  • binds directly to PAR6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells
  • WDR83 interacts with the apical transmembrane protein CRB3 to promote PARD6A- Atypical protein kinase C (aPKC) binding to CRB3, which is reinforced with the apically localized small GTPase CDC42
  • CRB3 promotes the interaction between YAP1 and the Hippo pathway kinases LATS1/2 at apical cell junctions to induce YAP1 phosphorylation and cytoplasmic retention, which drive cell differentiation
  • YAP1 promotes myelin and non-myelin genes transcription while the polarity protein CRB3, localized at the tips of the myelin sheath, activates the Hippo pathway to temper YAP1 activity, therefore allowing for optimal myelin growth
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    favors tumor cell growth, metastasis and epithelial to mesenchymal transition (EMT)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may be used as a new independent favorable prognostic factor for clear cell renal cell carcinoma
  • Therapy target
    ANIMAL & CELL MODELS