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FLASH GENE
Symbol DLG3 contributors: mct/pgu - updated : 12-10-2017
HGNC name discs, large homolog 3 (neuroendocrine-dlg, Drosophila)
HGNC id 2902
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a NMDA receptor binding site in the N-terminal domain, which is specific for the GRIN2B subunit
  • three Dlg (DHR/GLGZ/PDZ) motifs
  • PPXY motifs
  • a SH3 domain and a C terminal GUK domain, implicated in stabilization of DLG3
  • PDZ, SH3, and guanylate kinase (GK)-like domains, mediate specific protein-protein interactions
  • mono polymer octamer
    HOMOLOGY
    interspecies homolog to Drosophila tumor suppressor gene,discs large (Dlg)
    Homologene
    FAMILY MAGUK (membrane associated guanylate kinase homolog) superfamily
    CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • putative negative regulator of cell proliferation, through its interaction with APC, critical for synaptogenesis
  • playing a role in the clustering and targeting of NMDA receptors in the postsynaptic density of excitatory synapses
  • regulate the synaptic trafficking of distinct glutamate receptor subtypes at different developmental stages, thereby playing necessary roles in excitatory synapse development
  • DLG4, DLG2 and DLG3 are thought to have crucial roles in both AMPA receptor trafficking and formation of NMDA receptor-associated signalling complexes involved in synaptic plasticity
  • DLG4, DLG3, DLG1, and DLG3 are central organizers of the postsynaptic density at excitatory synapses on pyramidal neurons
  • scaffolding protein for ionotropic glutamate receptors at excitatory synapses
  • has unique roles in cortical synapse development by mediating EPHB1 and its downstream PAK1 signaling pathway
  • is a scaffolding protein abundantly expressed early in development that mediates glutamate receptor trafficking during synaptogenesis
  • is proposed to play a role in stabilizing receptors at immature synapses
  • CELLULAR PROCESS cell cycle, division
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • synapse formation mediated by EPHB1/DLG3/PAK1 signaling in the early postnatal brain may be crucial for cognitive development
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to APC
  • interacting with EXOC4 involved in the delivery of NMDARs (N-methyl-D-aspartate receptor) to the cell surface in heterologous cells and neurons
  • interaction between DLG3 and GRIN2B is PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain independent and is regulated by alternative splicing of DLG3
  • exerts a distinct function by recruiting the ubiquitin ligases NEDD4 and NEDD4L through its PPXY motifs (interactions required for DLG3 monoubiquitination, apical membrane recruitment, and tight junction consolidation)
  • binds the C-terminal part of the scaffolding protein neurobeachin (NBEA)
  • direct binding of NMDA receptors with DLG3 is involved in the efficient targeting of NMDA receptors to the synapses, whereas ligand binding of the PDZ domains is not essential for the synaptic clustering of DLG3
  • binds directly to N-methyl-D-aspartate receptors (NMDARs), anchors receptors at synapses, and facilitates transduction of NMDAR signals
  • role of DLG3 in the regulation of NMDAR trafficking
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MRX90
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    caused a reduction in the total number of thalamocortical (TC) axons innervating the somatosensory cortex, but did not affect the segregation of barrels
    tumoral     --low  
    in human brain Glioblastoma multiforme (GBM)tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS