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Symbol DLG1 contributors: shn/pgu - updated : 28-08-2015
HGNC name discs, large homolog 1 (Drosophila)
HGNC id 2900
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineadrenal gland    
Lymphoid/Immunelymph node   highly
Nervousnervespinal nervesciatic  
Reproductivefemale systembreastmammary gland highly
 female systemovary  highly
Respiratoryrespiratory tractlarynx  highly
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumcardiacmyocardium  Homo sapiens
SystemCellPubmedSpeciesStageRna symbol
Muscularmyocyte Homo sapiens
cell lineage
cell lines
  • 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
    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
  • MAGUK (membrane-associated guanylate kinase homolog) superfamily
  • CATEGORY structural protein , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
  • 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
    a component
  • component of the exocyst complex that has been previously implicated in SLC2A4 trafficking
  • GJB1 exists in a complex with DLG1 and CALM1
    small molecule
  • 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
    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
    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
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • 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)