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FLASH GENE
Symbol PALS1 contributors: npt/mct/pgu - updated : 24-05-2017
HGNC name protein associated with LIN7 1, MAGUK p55 family member
HGNC id 18669
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a PDZ/DHR domain
  • a central SH3 domain + HOOK domain, interacting with the C-terminus of MPP1
  • a C terminal GUK domain, also containing a EPB41 binding domain
  • a L27 domain targeting MPP to tight junction
  • guanylate kinase like (GUK) domain
  • conjugated LipoP
    HOMOLOGY
    interspecies ortholog to Drosophila Stardust (Sdt)
    ortholog to murine Mpp5
    homolog to C.elegans C01B7.4
    homolog to zebrafish nagie oko
    Homologene
    FAMILY
  • MAGUK family
  • CATEGORY adaptor , storage , signaling
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    basic FUNCTION
  • scaffold protein that targets to the tight junction in epithelia
  • required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton
  • involved in intracellular signaling cascade
  • required for correct localization of CRB1 at the subapical region in polarized Muller glia cells
  • may play a role in tight junctions biogenesis and in the establishment of cell polarity in epithelial cells
  • playing a role in the biogenesis of adherens junction
  • may be essential for the maintenance of epithelial cell polarity
  • polarity protein which plays an essential role in the radial and longitudinal extension of the myelin sheath, likely involving a functional role in membrane protein trafficking
  • roles in cell survival through interactions with MTOR signaling
  • participates to the optimal activation of NFKB1 following TCR stimulation
  • important functions in the retinal pigment epithelium in addition to the neural retina
  • indispensible role in retinal development, likely involving the maintenance of retinal polarity and survival of retinal neurons
  • its function is likely essential for laminar formation in both embryonic and postnatal retinas
  • encodes a scaffolding protein essential for the assembly and function of the CRB polarity complex in epithelial tissues, including the retina
  • specifically required for full maturation of photoreceptor cells
  • role of the canonical polarity protein MPP5 in radial sorting of axons by Schwann cells
  • is not only essential for cerebellum organogenesis, but also for preventing premature differentiation and thus maintaining progenitor pools in cerebellar germinal zones, including cerebellar granule neuron precursors in the external granule layer
  • is a novel intrinsic factor that regulates the generation of cerebellar cells and its deficiency is a potential inhibitor of overactive mitogenic signaling
  • core component of the apical membrane-determining CRB complex in the nephron
  • functions as a dose-dependent upstream regulator of the crosstalk between Hippo- and TGFB1-mediated signaling
  • new function of PALS1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • component of a complex with CRB1 and INADL
  • part of CRB1-membrane-associated palmitoylated protein (MPP)5 protein complex (may organize an intracellular protein scaffold in the retina involved in maintenance of photoreceptor-Müller glia cell adhesion)
  • member of the mammalian CRB-MPP5 polarity complex
  • importance of the FAT4-DCHS1-MPP5 complex in organizing the apical membrane architecture of neural progenitor cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to LIN7A
  • interacts with CRB3 and MPDZ
  • interacts with INADL, PARD6B, and EZR (essential role of ezrin (EZR)-PALS1 interaction in the apical membrane remodeling associated with parietal cell secretion)
  • interacting with MPP1 and whirlin
  • FAT4 is associated and colocalized with the MPP5 complex
  • MPDZ and INADL are closely related scaffold proteins and bind to many common interactors including MPP5 (protein associated with Lin seven) a member of the Crumbs complex
  • functional interaction of CDH5 with the cell polarity protein PALS1
  • biological activity of CDH5 in regulating endothelial polarity and vascular lumen formation is mediated through its interaction with the two cell polarity proteins PALS1 and PARD3
  • C-terminal PDZ binding motifs of SARS-CoV-1 and SARS-CoV-2 E proteins bind the PALS1 PDZ domain
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    leads to the disruption of the apical localization of Crb proteins in retinal progenitors and the adult retina, validating their mutual interaction
    tumoral     --low  
    in colorectal cancer, correlating with poorer survival of patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Pals1 mutant mouse exhibits the critical features of LCA such as early visual impairment as assessed by electroretinogram, disorganization of lamination and apical junctions and retinal degeneration