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FLASH GENE
Symbol SCRIB contributors: mct/pgu - updated : 24-03-2012
HGNC name scribbled homolog (Drosophila)
HGNC id 30377
Location 8q24.3      Physical location : 144.873.089 - 144.897.549
Synonym name
  • scribble
  • protein LAP4
  • Synonym symbol(s) SCRB1, CRIB1, Vartul, KIAA0147
    DNA
    TYPE functioning gene
    STRUCTURE 24.46 kb     37 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    MGC3113 8q24 hypothetical protein MGC3113 RHPN1 8q24.3 rhophilin, Rho GTPase binding protein 1 LOC389692 KIAA0150 8q24.3 rhophilin, Rho GTPase binding protein 1 LOC389693 8 LOC389693 FLJ12150 8q24.3 hypothetical protein FLJ12150 LOC389694 8 similar to FLJ46354 protein PP3856 8q24.3 similar to CG3714 gene product EEF1D 13q12 eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein) TIGD5 8q24.3 tigger transposable element derived 5 FLJ13852 8q24.3 hypothetical protein FLJ13852 TSTA3 8q24.3 tissue specific transplantation antigen P35B KIAA0628 8q24.3 tissue specific transplantation antigen P35B LOC286075 8q24.3 hypothetical protein LOC286075 LOC286076 8q24.3 similar to hypothetical protein ERK8  extracellular signal-regulated kinase 8 FLJ46072 8q24.3 FLJ46072 protein LOC389695 8 LOC389695 LOC389696 8 LOC389696 LOC286080 8q24.3 similar to CG3104-PA SCRIB 8q24.3 similar to CG3104-PA SIAHBP1 8q24.2-qtel similar to CG3104-PA LOC340371 8q24.3 hypothetical protein LOC340371 LOC389697 8 similar to epiplakin LOC392274 8 similar to cDNA sequence BC024139 PLEC1 8q24 plectin 1, intermediate filament binding protein 500kDa FLJ14464 8q24.3 hypothetical protein FLJ14464 GRINA 8q24 glutamate receptor, ionotropic, N-methyl D-asparate-associated protein 1 (glutamate binding) MGC61633 8q24.3 similar to Putative protein C21orf56 LOC392275 8 similar to sphingomyelin phosphodiesterase 3, neutral membrane (neutral sphingomyelinase II) OPLAH 8q24 5-oxoprolinase (ATP-hydrolysing) RRP41 8q24.3 exosome complex exonuclease RRP41 GPAA1 8q24.3 GPAA1P anchor attachment protein 1 homolog (yeast)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - 5201 - 1630 - 2006 16611247
    - - 5109 - 1601 - 2006 16611247
    - - 5276 - 1655 - 2006 16611247
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
    Endocrinepancreas    
    Nervousnerve   highly
    Respiratorylung    
    Skin/Tegumentskin   highly
    Urinarykidney    
    Visualeye   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 18 leucine-rich (LRR) repeats
  • four PDZ(DHR) domains
  • mono polymer heteromer , complex
    HOMOLOGY
    interspecies homolog to drosophila tumor suppressor Scribble
    Homologene
    FAMILY
  • LAP (LRR and PDZ) protein family
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • localized to cell junctions
  • co-localized with APC at the synaptic sites of hippocampal neuron and at the tip of membrane protrusion in the epithelial cell line
  • instead of a membrane association seen in normal epithelia, tumor-associated SCRIB is mislocalized and found predominantly in the cytosol
  • basic FUNCTION
  • playing a role in planar cell polarity
  • may be required for polarization of epithelia
  • may participate in the DLG1-APC complex through its PDZ domains and regulate cell cycle and neural function by associating with APC
  • participating in oncogenic processes
  • implicated in vesicle trafficking in neurons and receptor recycling in thyroid cells
  • playing a role in cell migration
  • crucial regulator of brain development and spine morphology
  • apical-basal polarity determinant and an essential component of the adherens junction
  • critical contributor to the clustering of immature T cells, an event shown here to be necessary for efficient developmental progression
  • Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity
  • negatively regulate the MAPK cascade to suppress tumorigenesis
  • in epithelial cancer cells, SCRIB is an upstream activator of the Hippo pathway leading to WWTR1 inhibition
  • CELLULAR PROCESS cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forming a complex Scrib-ARHGEF7-GIT1
  • part of DLG1/SCRIB/LLGL1 tumour suppressor complex, interacting with tSNARE syntaxin 4
  • ARHGEF7 forms a complex with cadherin, CTNNB1, and SCRIB at synapses and enhances localized actin polymerization in rat hippocampal neurons
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to k-ras and n-ras
  • interacting with APC and LPP
  • interacting through its PDZ domains with VANGL2
  • also interacting with TRIP6
  • interacting with UBE3A through its PDZ domains and C-terminal PDZ domain-binding motif of UBE3A protein
  • interacting with Tax protein and this complex is present in human T cell leukemia virus type 1-infected T cells
  • interacting with the E6 oncoprotein encoded by HPV16
  • interacting through its PDZ domains with ARHGEF7
  • interaction between p21-activated kinase proteins and Scrib-ARHGEF7-GIT1 complex
  • interacting with MCC
  • SCRIB-NOS1AP association is direct and is mediated through the phosphotyrosine-binding (PTB) domain of NOS1AP and the fourth PDZ domain of SCRIB
  • a functional interaction between PHLPP1 and SCRIB in negatively regulating AKT signalling
  • cell & other
    REGULATION
    inhibited by Tax protein
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    deregulation strongly correlated with poor survival in human prostate cancer
    tumoral     --low  
    and changed localization of SCRIB were associated with clinical stage, histopathological differentiation, and lymph node metastasis in endometrial cancer
    Susceptibility to craniorachischisis (CRN)
    Variant & Polymorphism other
  • missense variants in SCRIB may represent a cause of CRN
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Scrib1-deficient mice exhibit enhanced learning and memory abilities and impaired social behavior, two features relevant to autistic spectrum disorders
  • in Drosophila, loss of Scribbled (Scrib), a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc