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Symbol SCRIB contributors: mct/pgu - updated : 24-08-2016
HGNC name scribbled homolog (Drosophila)
HGNC id 30377
  • 18 leucine-rich (LRR) repeats
  • four PDZ(DHR) domains
  • mono polymer heteromer , complex
    interspecies homolog to drosophila tumor suppressor Scribble
  • LAP (LRR and PDZ) protein family
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
  • 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
  • NOS1AP colocalizes with both SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells, but does not colocalize with either SCRIB or VANGL1 at cell junctions in normal breast cells
  • 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
  • ERBIN, LRRC1, and SCRIB act at the post-synaptic membrane of NMJs in a concerted fashion to regulate nicotinic acetylcholine receptors cluster morphology and neural transmission
  • CELLULAR PROCESS cell migration & motility
    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
    small molecule
  • 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
  • when CD74 is overexpressed in cancer and noncancerous epithelial cells, it interacts and interferes with the function of SCRIB, a product of a well-known tumor suppressor gene
  • ZDHHC7-mediated SCRIB palmitoylation is critical for SCRIB membrane targeting, cell polarity and tumor suppression
  • cell & other
    inhibited by Tax protein
    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
    Therapy target
  • 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