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FLASH GENE
Symbol DLG1 contributors: shn/pgu - updated : 28-08-2015
HGNC name discs, large homolog 1 (Drosophila)
HGNC id 2900
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three DLG, (DHR/GLGZ/PDZ) motifs
  • a SH3 domain
  • a L27 domain, that may regulate DLG1 self-association
  • two binding sites for protein 4.1
  • a domain containing three PSD-95/Dlg/ZO-1 (PDZ) repeats
  • an alternatively spliced I3 domain
  • C-terminal guanylate kinase (GK) domain of DLG1 binds peptides with a phosphorylated serine residue
    • mono polymer homomer , tetramer
    HOMOLOGY
    interspecies homolog to Drosophila tumor suppressor gene,discs large (Dlg) 1
    ortholog to Dlg1, Mus musculus
    ortholog to Dlg1, Rattus norvegicus
    ortholog to dlg1, Danio rerio
    ortholog to DLG1, Pan troglodytes
    Homologene
    FAMILY
  • MAGUK (membrane-associated guanylate kinase homolog) superfamily
    • CATEGORY structural protein , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    text
  • localised at the adherent junctions of epithelial and endothelial cells
  • also associate with endoplasmic reticulum membranes
  • lies at the cellular junctions in G1, is enriched in the cytoplasm in S phase and locates to the mitotic spindle in M phase
  • SCN5A and DLG1 are both localized at intercalated discs
    • basic FUNCTION
  • plays important roles in regulating cell proliferation, epithelial cell polarity, and synapse formation and function
  • involved in coupling the cytoskeleton to the cell membrane
  • required for the proper organization of the actin cytoskeleton and for the morphological elongation of embryos
  • may play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation
  • may be a determinant in E-cadherin-mediated adhesion and signaling in epithelial cells
  • involved in the control of both cell polarity and maintenance of tissue architecture
  • required for adherens junction assembly and differentiation of human intestinal epithelial cells
  • has structural and signal transduction functions, participating in the organization of adherens junctions together with E-cadherin (CDH1)
  • regulates smooth muscle orientation in ureter
  • essential for normal urogenital morphogenesis and the development of skeletal and epithelial structures
  • may be a critical mediator of signals triggered by the antigen receptor complex in T lymphocytes by functioning as a scaffold coordinating the activities of T-cell receptor (TCR) signaling proteins at the immune synapse
  • functions as a negative regulator of TCR-induced proliferative responses
  • participates in the control of TGFalpha bioavailability through its dynamic interaction with the growth factor precursor and ADAM17
  • required for the retention and trafficking of NMDARs in this endoplasmic reticulum subcompartment
  • has a specific role in the forward trafficking of GluR1 through somatic Golgi
  • implicated in trafficking many types of proteins important for cellular function, including ion transporters, voltage-gated ion channels, and ligand-gated receptors
  • involved in patterning the dendritic arbor
  • DLG4, DLG3, DLG1, and DLG3 are central organizers of the postsynaptic density at excitatory synapses on pyramidal neurons
  • DLG1 and DLGAP1 control the forces operating on microtubules and play a fundamental role in centrosome positioning and cell polarity
  • multidomain scaffold protein implicated in the forward trafficking and synaptic localization of NMDA- and AMPA-type glutamate receptors
  • controls Treg function independently of the negative feedback pathway mediated by PRKCQ and related adaptor CARMA1
  • scaffolding protein for ionotropic glutamate receptors at excitatory synapses
  • DLG1 and CASK play critical cooperative roles in maintaining the nephron progenitor population, potentially via a mechanism involving effects on FGF signaling
  • prominent role for PDZ2 and I3 domains of DLG1 in organizing the ADRB1 receptosome involved in connecting the ADRB1 to trafficking and signaling networks
  • modular scaffolding protein implicated in the control of cell polarity through assembly of specific multiprotein complexes, including receptors, ion channels and signaling proteins, at specialized zones of the plasma membrane
    • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the exocyst complex that has been previously implicated in SLC2A4 trafficking
  • GJB1 exists in a complex with DLG1 and CALM1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • lymphocyte-specific protein tyrosine kinase, LCK and potassium voltage-gated channel shaker-related subfamily member 3, KCNA3
  • E-cadherin, ECAD
  • A kinase (PRKA) anchor protein 5, AKAP5
  • kinesin family member 13B, KIF13B
  • APC-hDLG complex formation plays an important role in transducing the APC cell cycle blocking signal
  • leucine rich repeat containing 1, LRRC1
  • glutamate receptor ionotropic AMPA 1, GRIA1
  • solute carrier family 9 (sodium/hydrogen exchanger) member 3 regulator 1, SLC9A3R1
  • glutamate receptor, ionotropic kainate 2, GRIK2
  • potassium inwardly-rectifying channel, subfamily J, member 12, KCNJ12
  • calcium/calmodulin-dependent serine protein kinase (MAGUK family), CASK
  • Tumor necrosis factor alpha converting enzyme, TACE
  • beta-transducin repeat containing, BTRC
  • mitochondrial ribosomal protein S-34, MRP-S34
  • potassium voltage-gated channel shaker-related subfamily member 5, KCNA5
  • glutamate receptor ionotropic N-methyl D-aspartate 2A, GRIN2A
  • tumor endothelial marker 5, TEM5
  • guanylate kinase-associated protein, GKAP
  • adrenergic beta-1- receptor, ADRB1
  • direct interaction with the GluA1 AMPAR subunit
  • MTMR2 in Schwann cells, interacts with Discs large 1 (DLG1), a scaffold involved in polarized trafficking and membrane addition, whose localization in MTMR2-null nerves is altered
  • interaction with the EXOC4 exocyst component promoting membrane addition, whereas with MTMR2, negatively regulates membrane formation
  • DLG1 interacts with dynein via the scaffolding protein DLGAP1 and together, DLG1, DLGAP1, and dynein control microtubule dynamics and organization near the cell cortex and promote centrosome positioning
  • GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein GPSM2 in a phosphorylation-dependent manner
  • interaction of DLG1 with the activated form of MAP2K2 of the canonical RAF/MEK/ERK pathway, a protein that is found at the midbody during cytokinesis
  • DLG1, which acts as a scaffold for many signaling molecules including the TCR and LCK, could mediate the cellular redistribution of LCK during T-cell maturation
  • contributes to the stabilization of SCN7A at the plasma membrane
  • CRHR1 interacts with synapse-associated protein 97 (DLG1) (DLG1 is involved in coupling G protein-coupled receptors to the activation of the ERK1/2 signaling pathway)
  • the extreme C-terminus of ADRB1 binds DLG1 and AKAP5 to organize a scaffold involved in trafficking of the ADRB1
  • CASK binding regulates DLG1 conformation and its subsequent sorting and synaptic targeting of AMPARs and NMDARs during trafficking to synapses
  • ADRB1 associates with PDE4D8 through the receptor C-terminal PDZ motif-dependent binding to synaptic-associated protein 97 (DLG1)
  • GPER1 interacted with membrane-associated guanylate kinases, including DLG1 and DLG4, and protein kinase A-anchoring protein (AKAP5) in the plasma membrane in a PDZ-dependent manner
  • in hippocampal neurons, DLG1 an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes
  • PTEN regulates spindle pole movement through DLG1-mediated recruitment of KIF11 to centrosomes
    • cell & other
    REGULATION
    Other phosphorylated by both CDC2 and CDK2 on Ser158 and Ser442 (role for these phosphorylation events in controlling DLG1 protein stability, DLG1 localisation and function)
    SAP97/NR2A interaction is regulated by CaMKII-dependent phosphorylation
    ubiquitinated by membrane-associated ring finger (C3HC4) 2, MARCH2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    loss of DLG1 expression being associated with complete lack of cell polarity and tissue architecture during the latest stages of malignant progression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Dlgh1(-/-) mice developed severe urinary tract abnormalities, including congenital hydronephrosis
  • Dlg1-null mice exhibit hydronephrosis, hydroureter, and occasionally hypoplastic kidneys
  • deletion of mice Dlgh-1 caused open eyelids, open neural tube, and misorientation of cochlear hair cell stereociliary bundles, indicative of defects in planar cell polarity (PCP)