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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
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