Affinage

DLG1

Disks large homolog 1 · UniProt Q12959

Length
904 aa
Mass
100.5 kDa
Annotated
2026-06-09
100 papers in source corpus 59 papers cited in narrative 59 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLG1 (hDlg/SAP97) is a multidomain MAGUK scaffolding protein that organizes membrane signaling microdomains at epithelial junctions, neuronal synapses, the immune synapse, the mitotic cortex, and the cardiomyocyte membrane by clustering and trafficking transmembrane receptors and channels through its three PDZ domains, SH3 region, and a catalytically inactive guanylate kinase-like (GK) domain (PMID:7937897, PMID:9523702). Subcellular targeting and cytoskeletal attachment are governed by an N-terminal region and alternatively spliced inserts: the unique SAP97 N-terminus and the I3 insert direct it to the epithelial lateral membrane and cell-cell contacts via protein 4.1/ERM and the CASK/MPP7-LIN7 L27-domain complexes, while the I2 insert directs nuclear localization (PMID:8922391, PMID:9683631, PMID:11723125, PMID:11865057, PMID:17237226). In neurons, SAP97 binds the AMPA receptor subunit GluA1 (PDZ-dependent) and the NMDA receptor subunit NR2A (PDZ1), and its CASK-controlled monomer-dimer/compact-extended conformational switch sorts these receptors: compact SAP97 favors GluA1-AMPARs while CASK-bound extended SAP97 favors GluN2B-NMDARs (PMID:9677374, PMID:12933808, PMID:15504326, PMID:23864692). CaMKII phosphorylation orchestrates this trafficking, driving SAP97 to the postsynaptic compartment via Ser39 and disrupting NR2A binding via Ser232 to trigger receptor insertion (PMID:12933808, PMID:17156128); SAP97 and CASK route NMDARs through a specialized dendritic ER/Golgi-outpost pathway (PMID:19620977). Distinct palmitoylated alpha and L27-containing beta isoforms partition AMPARs into subsynaptic domains and exert opposite effects on synaptic potentiation (PMID:19357261, PMID:21768261). In epithelia DLG1 couples to E-cadherin-based junctions, is stabilized by cell contact and degraded by the proteasome, and its release from cytoskeletal GKAP tethering is triggered by p38gamma phosphorylation during osmotic stress (PMID:9512503, PMID:11739660, PMID:15729360); it further scaffolds Scribble-SGEF-RhoG to control actomyosin contractility and barrier function (PMID:31248911) and is required for canonical Wnt/beta-catenin signaling in retinal endothelium (PMID:31066677). In dividing cells DLG1 localizes to the basolateral cortex and binds LGN to orient the mitotic spindle, and is recruited by PTEN with Eg5 to centrosomes to build bipolar spindles and ensure faithful chromosome segregation (PMID:25202028, PMID:27240320). In T cells DLG1 scaffolds an Lck-Zap70-WASp complex and an alternative p38-NFAT signaling pathway at the immune synapse, dependent on ezrin-controlled localization (PMID:15699074, PMID:17187070, PMID:20551903). In the heart DLG1 anchors potassium channels (Kv4.x, Kir2.x, Kv1.5) and the sodium channel Nav1.5, and cardiac-specific ablation selectively reduces potassium currents and prolongs action potential duration while leaving INa intact (PMID:19213956, PMID:21164104, PMID:25447080); it also maintains beta1-adrenergic receptor signaling integrity, with loss shifting beta1AR toward arrestin-CaMKII signaling and cardiac remodeling (PMID:32507058). DLG1 is additionally targeted by viral oncoproteins (Ad9 ORF1, HTLV-1 Tax, HPV-18 E6) through PDZ-binding motifs, and Tax binding disrupts the DLG1-APC interaction that underlies DLG1-mediated G0/G1 cell-cycle arrest (PMID:9192623, PMID:10557085, PMID:10656683, PMID:17713926).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 Medium

    Establishing DLG1's domain architecture and its association with the membrane-cytoskeleton adaptor protein 4.1 defined it as a junction-localized scaffold rather than an enzyme.

    Evidence cDNA cloning, in vitro binding with recombinant protein 4.1, and immunolocalization

    PMID:7937897

    Open questions at the time
    • Did not define which PDZ domains engage transmembrane partners
    • No functional consequence of 4.1 binding established
  2. 1996 High

    Domain dissection showed that the PDZ1-2 unit and the alternatively spliced I3 insert provide redundant targeting routes binding 4.1/ERM and T/SXV-motif partners, explaining how DLG1 reaches cell-cell contacts.

    Evidence In vitro domain binding, domain-deletion localization in permeabilized cells, and co-IP of 4.1 and ezrin

    PMID:8922391

    Open questions at the time
    • Did not identify the physiological transmembrane ligands at junctions
    • Conformational regulation of targeting unaddressed
  3. 1998 High

    Resolving the unique SAP97 N-terminal 65 residues as the primary lateral-membrane targeting determinant, and demonstrating the GK domain lacks guanylate kinase activity, recast DLG1 as a localization-driven, enzymatically inert scaffold; concurrent identification of GluA1 binding linked it to glutamate receptors.

    Evidence Domain-deletion mutagenesis with fractionation/IF; in vitro GK enzymatic assay; co-IP of GluR1 from rat brain with recombinant binding

    PMID:9523702 PMID:9677374 PMID:9683631

    Open questions at the time
    • Mechanism coupling the N-terminus to the cytoskeleton not resolved
    • GluA1 binding specificity vs other AMPAR subunits explained but trafficking role not yet shown
  4. 1997 High

    Discovery that viral oncoproteins (Ad9 ORF1, HTLV-1 Tax, HPV-18 E6) bind DLG1 PDZ domains, and that DLG1 binds APC and arrests the cell cycle, established a tumor-suppressor axis disrupted by viral hijacking.

    Evidence Library screen, in vitro/in vivo binding, co-IP from infected T cells, and BrdU/cell-cycle assays with domain mutants

    PMID:10557085 PMID:10656683 PMID:9192623 PMID:9286858

    Open questions at the time
    • How APC binding mechanistically blocks G1/S transition not defined
    • Endogenous (non-viral) regulators of the DLG1-APC axis unknown
  5. 2000 Medium

    Identifying CASK GUK-SH3 binding and demonstrating that SAP97 retains Kv1 channels in the ER while distinct from PSD-95 revealed DLG1 as a biosynthetic-trafficking scaffold, not merely a surface-clustering one.

    Evidence Yeast two-hybrid, GST binding, co-IP, and heterologous channel surface/IF analysis

    PMID:10629225 PMID:10993877

    Open questions at the time
    • Whether ER retention reflects a regulated trafficking checkpoint not established
    • CASK's role in DLG1 conformation not yet probed
  6. 2001 High

    Mapping channel partners (Kir2.x via PDZ2, Kv1.5 via TDL motif) and the conserved CASK L27N-SAP97 N-terminal interaction tied DLG1 to cardiac/epithelial channel localization and defined the L27 module controlling targeting and oligomerization.

    Evidence GST pulldown from native tissue, co-IP, mutagenesis, oocyte patch clamp, dominant-negative CASK in MDCK, and Drosophila conservation

    PMID:11181181 PMID:11694581 PMID:11709425 PMID:11723125 PMID:11865057

    Open questions at the time
    • Whether PKA regulation of channel binding occurs in vivo not shown
    • Stoichiometry of the SAP97-CASK-channel complex undefined
  7. 2003 High

    Demonstrating CaMKII phosphorylation of SAP97 Ser232 within PDZ1 disrupts NR2A binding provided the first phosphoregulatory switch coupling kinase activity to receptor release.

    Evidence In vitro pulldown, co-IP from synaptosomes, metabolic labeling, CaMKII inhibition, and phosphomimetic mutants

    PMID:12933808

    Open questions at the time
    • Did not connect the switch to receptor surface insertion
    • Other CaMKII sites and their order unresolved
  8. 2004 High

    Linking the L27-controlled monomer-dimer transition to AMPAR synaptic delivery and LTP, while RNAi knockdown impaired AMPA and NMDA transmission, established SAP97 multimerization as functionally required for synaptic strength.

    Evidence Single-particle EM, RNAi, EPSC electrophysiology, L27 mutants, and FRAP

    PMID:15504326

    Open questions at the time
    • Direct structural basis of the compact-extended switch not yet visualized
    • Redundancy with other PSD-MAGUKs not assessed
  9. 2005 High

    Identifying p38gamma phosphorylation as the trigger releasing SAP97 from GKAP/cytoskeleton, and the Cdc42-Par6-PKCzeta pathway promoting DLG1-APC for migratory microtubule polarization, extended DLG1 regulation to stress responses and directed cell migration.

    Evidence In vitro kinase assays, co-IP, phosphosite mapping, osmotic stress, RNAi, and TIRF imaging in astrocytes

    PMID:15729360 PMID:16157700

    Open questions at the time
    • How GKAP release alters junctional integrity mechanistically not fully defined
    • Direct kinase-substrate stoichiometry in migration unresolved
  10. 2006 High

    Defining isoform-specific synaptic roles (palmitoylated alpha vs L27 beta) and the requirement of DLG1 for TCR-induced alternative p38-NFAT signaling and immune-synapse organization broadened DLG1 into activity-dependent and immune scaffolding.

    Evidence Isoform rescue electrophysiology with CaMKII inhibition; siRNA/mutant rescue with NFAT reporters; Lck/Zap70/WASp co-IP and imaging; AKAP79-beta1AR PKA scaffold co-IP

    PMID:15699074 PMID:16815335 PMID:17156128 PMID:17170109 PMID:17187070

    Open questions at the time
    • How a single scaffold selectively activates p38-NFAT but not JNK/NF-kB not mechanistically resolved
    • Isoform expression regulation in vivo unaddressed
  11. 2007 High

    Structural and partner-mapping work (PDZ2-E6 NMR with non-canonical six-residue binding, TACE/ADAM17 via PDZ3, Delta1, MPP7-LIN7 L27 complex) detailed the diverse PDZ/L27 engagement modes underlying DLG1 specificity.

    Evidence NMR/ITC, yeast two-hybrid, co-IP, domain deletions, and shedding/migration assays

    PMID:12668732 PMID:15485825 PMID:17237226 PMID:17435047 PMID:17713926

    Open questions at the time
    • Whether the non-canonical PDZ2 mode generalizes to endogenous ligands unclear
    • Knockout urogenital phenotype mechanism (proliferation vs junctions) not molecularly explained
  12. 2009 High

    Defining a specialized SAP97-CASK NMDAR ER/Golgi-outpost trafficking route, the cardiac SAP97-Kv4-CaMKII complex, the AKAP79 splice-variant phosphoswitch, and GluA1-driven membrane translocation integrated DLG1 into compartment-specific receptor and channel delivery.

    Evidence Live imaging, RNAi, fractionation, co-IP from cardiomyocytes, patch clamp, GST binding, and dendritic morphometry

    PMID:18842882 PMID:19213956 PMID:19357261 PMID:19620977 PMID:19858198 PMID:19895665

    Open questions at the time
    • Molecular machinery routing cargo to dendritic Golgi outposts not fully defined
    • Relative contributions of multiple CaMKII sites in vivo unresolved
  13. 2010 High

    Cardiac Nav1.5 anchoring at intercalated discs, the Cdc42-Dlg1-GKAP-dynein control of centrosome positioning, ezrin-dependent immune-synapse localization, and conditional-KO redundancy with PSD-MAGUKs delineated context-specific essential and dispensable roles.

    Evidence Pulldown, RNAi, patch clamp, mdx comparison, live imaging, co-IP, and conditional KO with rescue electrophysiology

    PMID:20133708 PMID:20551903 PMID:21041448 PMID:21164104

    Open questions at the time
    • Compensating MAGUKs in mature neurons not identified at the molecular level
    • How DLG1 partitions Nav1.5 between intercalated discs and lateral membrane not resolved
  14. 2013 High

    Direct demonstration that CASK binding stabilizes an extended SAP97 conformation preferring GluN2B-NMDARs while compact SAP97 prefers GluA1-AMPARs provided the conformational logic for differential receptor sorting; parallel work added EAAT2b, MARCH2-mediated ubiquitination, and PKC-dependent ADAM10 trafficking.

    Evidence Intramolecular FRET sensors, co-IP, colocalization, surface biotinylation, TAP-MS, and ubiquitination assays

    PMID:17980554 PMID:23864692 PMID:25429624 PMID:25834051

    Open questions at the time
    • What sets the equilibrium between compact and extended states in vivo unclear
    • Physiological MARCH2-DLG1 turnover regulation not established
  15. 2014 High

    Identifying direct Dlg1-LGN binding for planar spindle orientation established DLG1 as a cortical determinant linking the cell-cortex scaffold to mitotic machinery.

    Evidence Live spindle imaging, RNAi in chick and human cells, co-IP, and micropattern overexpression

    PMID:25202028

    Open questions at the time
    • Upstream cues localizing Dlg1 to the basolateral cortex during mitosis not defined
    • Relationship to the PTEN-Eg5 centrosomal role not yet integrated
  16. 2016 High

    Demonstrating PTEN-dependent recruitment of Dlg1-Eg5 to centrosomes for bipolar spindle assembly, and Kif13b/p38gamma-controlled Dlg1 stability regulating PI3K/AKT in glia, expanded DLG1 into centrosomal spindle control and myelination-linked AKT signaling.

    Evidence Genetic mouse models, co-IP, centrosome fractionation, live imaging, aneuploidy assays, and conditional Kif13b KO with phospho/ubiquitination analysis

    PMID:27070899 PMID:27240320

    Open questions at the time
    • How DLG1 mechanically supports spindle-pole motility not fully resolved
    • Cell-type-specific opposite outcomes of Dlg1 turnover not mechanistically reconciled
  17. 2019 High

    Showing endothelial Dlg1 is required for canonical Wnt/beta-catenin signaling and that Dlg1 scaffolds Scribble-SGEF-RhoG for actomyosin/barrier control connected DLG1 to developmental signaling and junctional contractility.

    Evidence EC-specific KO, genetic epistasis, CRISPR reporter cells, beta-catenin rescue, co-IP, and 3D cyst assays

    PMID:31066677 PMID:31248911

    Open questions at the time
    • Direct molecular link between Dlg1 and the beta-catenin destruction complex not defined
    • Whether Scribble-Dlg1-SGEF acts in vivo at endothelial junctions untested
  18. 2020 High

    Cardiac-specific KO work showed SAP97 maintains beta1AR signaling fidelity, with GRK5-driven dissociation shifting beta1AR toward arrestin-CaMKII and Epac-CaMKII activation and pathological remodeling, defining a protective cardiac signaling role.

    Evidence Cardiac-specific deletion, GRK5 epistasis, co-IP, CaMKII activity assays, and cardiac function measurements

    PMID:32507058

    Open questions at the time
    • How SAP97 biases beta1AR away from arrestin coupling structurally unresolved
    • Therapeutic exploitability of the SAP97-beta1AR axis untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DLG1's conformational state, isoform/splice composition, and phosphorylation code are integrated to select among its many partners within a single cell remains the central open question.
  • No unified structural model of how PDZ/L27/SH3-GK states combinatorially set partner choice
  • Quantitative rules governing tissue-specific partner selection not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 4 GO:0005856 cytoskeleton 4 GO:0005815 microtubule organizing center 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-9609507 Protein localization 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-397014 Muscle contraction 3
Partners
AKAP79APCCASKEZRGKAPGRIA1GRIN2ALGN
Complex memberships
Lck-Dlg1-Zap70-WASp immune synapse complexMPP7-LIN7-DLG1 L27 complexSAP97-CASK-Veli-Mint1 channel trafficking complexScribble-Dlg1-SGEF complex

Evidence

Reading pass · 59 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 hDlg (DLG1) contains three PDZ domains, an SH3 region, and a guanylate kinase-like domain. Two sites within hDlg associate in vitro with the 30-kDa N-terminal domain of protein 4.1, and the protein localizes to regions of cell-cell contact. In vitro binding assay with recombinant proteins; cDNA cloning and sequencing; immunolocalization Proceedings of the National Academy of Sciences of the United States of America Medium 7937897
1995 SAP97 localizes at the presynaptic nerve termini of excitatory synapses in hippocampus and at basolateral membranes of epithelial cells, suggesting a role in the site-specific assembly of membrane specializations at cell-cell contacts. Light and immunoelectron microscopy of rat hippocampal formation and epithelial cells The Journal of neuroscience Medium 7891172
1996 DLG1 subcellular targeting requires either the PDZ1-2 conformational unit (which binds protein 4.1/ERM proteins and T/SXV motif-containing proteins) or the alternatively spliced I3 domain (which binds exclusively 4.1/ERM proteins). Both protein 4.1 and ezrin interact with DLG1 in co-precipitating immune complexes. In vitro binding assays with recombinant protein domains; in situ localization of domain constructs in permeabilized cells; co-immunoprecipitation The Journal of cell biology High 8922391
1997 Adenovirus 9ORF1 oncoprotein interacts directly with the second PDZ domain of hDlg/SAP97 in vitro and in vivo. HTLV-1 Tax and HPV-18 E6 oncoproteins also bind DLG1 in vitro via their C-terminal PDZ-binding motifs. Lambda gt11 library screen; in vitro binding assays; co-immunoprecipitation from cells Proceedings of the National Academy of Sciences of the United States of America High 9192623
1997 DAP-1 (GKAP/SAPAP) binds to the guanylate kinase-like domains of hDLG and PSD-95, and associates with hDLG, NMDA receptors, and APC protein; it colocalizes with PSD-95 and NMDA receptors at synapses. Yeast two-hybrid; co-immunoprecipitation; immunofluorescence colocalization Genes to cells Medium 9286858
1998 SAP97 directly associates with the C terminus of GluR1 (AMPA receptor subunit) via its PDZ domains, but not with GluR2 or GluR3; SAP97 was present in AMPA receptor complexes immunoprecipitated from rat brain. Co-immunoprecipitation from rat brain; in vitro binding with recombinant proteins; cross-linking experiments The Journal of biological chemistry High 9677374
1998 The first 65 amino acid residues unique to SAP97 (absent from PSD-95/SAP90 and SAP102) direct selective subcellular localization to the epithelial lateral membrane and mediate cytoskeletal attachment; PDZ1-2 domains and I3 insert affect efficiency but are not essential for targeting. Domain deletion mutagenesis; subcellular fractionation; immunofluorescence in epithelial cells Journal of cell science High 9683631
1998 SAP97 is recruited to sites of E-cadherin-mediated cell-cell contact via an E-cadherin-induced assembly of the cortical cytoskeleton; SAP97 associates with the E-cadherin/catenin complex indirectly through cytoskeletal attachment. Immunofluorescence in epithelial CACO-2 cells and L-cells; biochemical fractionation; E-cadherin induction assays Journal of cell science Medium 9512503
1998 The guanylate kinase-like (GK) domain of SAP97 does not encode an active guanylate kinase — it lacks enzymatic activity and cannot be activated by GKAP; flanking regions do not act as inhibitory regulators. In vitro enzymatic assay; biochemical analysis of recombinant GK domain European journal of biochemistry High 9523702
1999 HTLV-1 Tax binds hDLG via the C-terminus of Tax and the PDZ domain of hDLG; Tax binding to hDLG prevents its interaction with APC, and co-expression of Tax suppresses hDLG-mediated cell cycle arrest (G0/G1 inhibition of BrdU incorporation). Yeast two-hybrid; in vitro binding; co-immunoprecipitation from HTLV-1-infected T-cells; microinjection/BrdU incorporation assay Oncogene High 10557085
1999 NR2A subunit C-terminal tSXV motif binds PDZ domains of SAP97 in yeast two-hybrid; upstream sequences beyond the tSXV motif are required for efficient interaction. NR1-3 and NR1-4, despite having tSXV motifs, do not interact with SAP97. Yeast two-hybrid; site-directed mutagenesis; immunohistochemistry The European journal of neuroscience Medium 10336672
2000 Overexpression of hDLG suppresses cell proliferation by blocking G0/G1 to S phase transition. This activity requires intact PDZ, SH3, and GK domains of hDLG, and is partially dependent on interaction with APC via its C-terminal S/TXV motif. Overexpression and domain mutant analysis; cell cycle analysis; APC co-expression studies Oncogene Medium 10656683
2000 SAP97 interacts with Kv1 potassium channels intracellularly and prevents biosynthetic trafficking, causing intracellular accumulation of Kv1 channels in ER-derived vesicles — distinct from PSD-95, which clusters channels at the plasma membrane. Co-expression in heterologous cells; immunofluorescence; cell surface expression analysis The Journal of cell biology Medium 10629225
2000 hCASK GUK domain binds the SH3 domain of hDlg; both proteins colocalize at basolateral epithelial membranes and co-precipitate from intestinal cell lysates. SH3 and GUK domains also participate in intramolecular interactions within each MAGUK. Yeast two-hybrid; GST fusion protein binding assays; co-immunoprecipitation; immunofluorescence The Journal of biological chemistry Medium 10993877
2001 SAP97 interacts with Kir2.1, Kir2.2, and Kir2.3 channels via the C-terminal SEI motif of Kir2.2 and the second PDZ domain of SAP97; PKA phosphorylation of the Kir2.2 C-terminus inhibits SAP97 association. Kir2.2 and SAP97 colocalize at T-tubules in cardiac ventricular myocytes. GST affinity pulldown from rat brain/heart; co-immunoprecipitation; mutagenesis; immunofluorescence Journal of cell science High 11181181
2001 The I3 alternatively spliced insertion targets hDlg to cell-cell contact membranes; I2 insertion targets it to the nucleus. The N-terminal alternatively spliced region binds SH3 domains and moderates protein oligomerization. Expression of isoform constructs; immunofluorescence localization; in vitro binding assays The Journal of biological chemistry Medium 11723125
2001 C. elegans DLG-1 (most similar to SAP97) localizes to adherens junctions via its N-terminal domain and recruits AJM-1 and CPI-1 to adherens junctions; loss of DLG-1 disrupts actin cytoskeleton organization and embryo elongation without affecting cell polarity. Genetic knockout in C. elegans; immunofluorescence; GFP localization; domain deletion analysis Molecular biology of the cell High 11694581
2001 hDlg is degraded via the proteasome, and upon cell-cell contact is hyper-phosphorylated and stabilized. In transformed and undifferentiated cervical cancer cells this contact-dependent stabilization is lost. Proteasome inhibitor treatment; western blot; immunofluorescence in epithelial cell lines at varying density Journal of cell science Medium 11739660
2001 SAP97 interacts with Kv1.5 potassium channel via the channel's C-terminal TDL motif; SAP97-Kv1.5 complexes are retained in the ER of COS-7 cells but SAP97 coexpression augments Kv1.5 currents in Xenopus oocytes. Co-immunoprecipitation; mutagenesis of Kv1.5 C-terminus; patch clamp in oocytes; immunocytochemistry American journal of physiology. Heart and circulatory physiology Medium 11709425
2002 The L27N domain of CASK binds the N-terminus of SAP97; this interaction is required for lateral membrane localization of SAP97 in MDCK epithelial cells. A Drosophila DLG isoform containing the SAP97 N-terminal equivalent binds Camguk (the CASK ortholog), showing evolutionary conservation. Biochemical L27 domain binding assays; dominant-negative CASK overexpression; colocalization in MDCK cells; Drosophila isoform analysis Molecular and cellular biology High 11865057
2003 SAP97 interacts with TACE (ADAM17) metalloprotease via the PDZ3 domain of SAP97 and the C-terminal sequence of TACE; overexpression of SAP97 (but not a PDZ3-deleted mutant) inhibits TACE shedding activity. Yeast two-hybrid; affinity purification; co-immunoprecipitation; immunofluorescence; TACE shedding assay Journal of cell science Medium 12668732
2003 SAP97 directly interacts with NMDA receptor subunit NR2A via its PDZ1 domain; CaMKII phosphorylates SAP97 at Ser-232 within PDZ1, disrupting the SAP97-NR2A interaction both in vitro and in transfected cells. In vitro pull-down; co-immunoprecipitation from hippocampal synaptosomes; metabolic labeling; CaMKII inhibitor treatment; phosphomimetic mutant expression The Journal of biological chemistry High 12933808
2004 SAP97 monomer-dimer transition is controlled by its N-terminal L27 domain. Overexpression of SAP97 drives GluR1 to synapses, potentiates AMPAR EPSCs, and occludes LTP; L27 domain mutants that prevent multimerization show faster synaptic turnover and loss of potentiation. RNAi knockdown of endogenous SAP97 reduces surface expression of both GluR1 and GluR2 and impairs both AMPA and NMDA EPSCs. Single-particle electron microscopy; RNAi knockdown; electrophysiology (EPSCs); overexpression with L27 mutants; FRAP Neuron High 15504326
2004 SAP97, CASK, Veli-1/3, and Mint1 form a multiprotein trafficking complex that associates with Kir2.1, Kir2.2, and Kir2.3 channels via the C-terminal PDZ-binding motif. Dominant-interfering CASK causes Kir2.2 mislocalization from the basolateral membrane in polarized epithelial cells. GST pulldown from brain; co-immunoprecipitation; in vitro protein interaction assays; immunocytochemistry; dominant-negative CASK expression The Journal of biological chemistry High 14960569
2005 p38γ (SAPK3) phosphorylates SAP97/hDlg, triggering its dissociation from GKAP and release from the cytoskeleton, regulating intercellular junction integrity in response to osmotic stress. In vitro kinase assay; co-immunoprecipitation; identification of phosphorylation sites; osmotic stress experiments The EMBO journal High 15729360
2005 Cdc42 activates Par6-PKCζ at the leading edge of migrating astrocytes, promoting Dlg1-APC interaction. This APC-Dlg1 physical interaction is required for polarization of the microtubule cytoskeleton during directed cell migration. RNAi knockdown; TIRF microscopy; biochemical co-immunoprecipitation; Cdc42 activation assays in migrating astrocytes The Journal of cell biology High 16157700
2005 Dlgh1 translocates to the immune synapse and lipid rafts upon TCR/CD28 engagement; Lck-SH3-mediated interactions control Dlgh1 membrane targeting. Dlgh1 facilitates formation of Lck-Dlgh1-Zap70-WASp complexes and promotes actin polymerization, synaptic raft/TCR clustering, and NFAT activation. Co-immunoprecipitation; RNAi knockdown; overexpression; immunofluorescence; NFAT reporter assay The Journal of experimental medicine High 15699074
2006 DLG1's palmitoylated α-isoform localizes to the postsynaptic density and influences AMPAR-mediated synaptic strength independently of activity; the L27-containing β-isoform primarily influences AMPAR function in a CaMKII-dependent, activity-regulated manner. The N-terminal domain determines isoform-specific roles in synaptic function. Silencing of endogenous PSD-95 + heterologous expression of isoforms; electrophysiology; CaMKII inhibitor experiments Neuron High 16815335
2006 Dlgh1 MAGUK scaffold protein is required for TCR-induced 'alternative' p38 activation and NFAT transcription but not JNK or NF-κB activation; a Dlgh1 mutant unable to bind p38 fails to activate NFAT. siRNA knockdown; overexpression of binding-defective mutant; NFAT and NF-κB reporter assays; p38 activation assays Nature immunology High 17187070
2006 CaMKII phosphorylates SAP97 on Ser39 in the N-terminal domain; this phosphorylation drives SAP97 to the postsynaptic compartment and releases the SAP97/NR2A complex from the ER. Subsequently, Ser232 phosphorylation within PDZ1 disrupts NR2A binding and triggers NR2A insertion into the postsynaptic membrane. Phospho-specific antibodies; CaMKII activation/inhibition in hippocampal neurons; mutagenesis (S39D, S232D); co-immunoprecipitation Journal of neurochemistry High 17156128
2006 SAP97 assembles an AKAP79-cAMP-dependent PKA scaffold at the C-terminal PDZ-binding motif (ESKV) of the β1-adrenergic receptor; this SAP97-AKAP79 complex is required for efficient β1-AR recycling and PKA-mediated phosphorylation of β1-AR Ser312. Co-immunoprecipitation; PDZ-motif mutagenesis; receptor trafficking assays; PKA phosphorylation assays The Journal of biological chemistry Medium 17170109
2007 SAP97 directs Kv4.2 (A-type K+ channel) to postsynaptic density (PSD) via PDZ domain interaction with Kv4.2 C-terminus; CaMKII-dependent SAP97 phosphorylation regulates Kv4.2 subcellular localization to spines. Co-immunoprecipitation; synaptic fractionation; SAP97 lentiviral RNAi; pharmacological SAP97 translocation to spines The Journal of biological chemistry Medium 17635915
2007 Delta1 (Notch ligand) interacts with Dlg1 via a C-terminal canonical PDZ-binding motif (ATEV); Delta1 expression triggers accumulation of Dlg1 at cell-cell contacts and reduces cell motility. These effects are abolished by deletion of the ATEV motif, independently of Notch signaling. Peptide affinity chromatography + mass spectrometry; co-immunoprecipitation; immunofluorescence; migration assay with PDZ-motif deletion mutant The Journal of biological chemistry Medium 15485825
2007 MPP7 forms a tripartite complex with LIN7A or LIN7C and DLG1. MPP7 dimerizes with LIN7 through L27 domains; the MPP7-LIN7 dimer then associates with DLG1's N-terminal L27 domain. MPP7 is required for localization of DLG1 to epithelial adherens junctions and stabilizes DLG1 in an insoluble compartment. Co-immunoprecipitation; domain deletion analysis; immunofluorescence in epithelial cells; detergent fractionation The Journal of biological chemistry Medium 17237226
2007 NMR solution structure of the hDlg PDZ2 domain bound to HPV-18 E6 C-terminal peptide shows a novel mode of interaction where six residues of the peptide contact PDZ2, compared to the typical four. Phosphorylation of E6 Thr156 disables binding. NMR structure determination; isothermal titration calorimetry; mutagenesis; molecular dynamics simulation Biochemistry High 17713926
2007 Dlg1 loss-of-function in mice causes abnormalities in renal/urogenital development (hypoplastic kidneys/ureters, absent vagina and seminal vesicle) associated with impaired epithelial cellular proliferation rather than disruption of cell-cell junctional complexes. Dlgh1 knockout mouse generation; histology; immunostaining for junctional markers; proliferation assays Development (Cambridge, England) Medium 17435047
2008 GluR1 binding to SAP97 via its C-terminal 7 aa is required to translocate SAP97 from the cytosol to plasma membranes; GluR1 and SAP97 together at the plasma membrane promote dendrite branching in an activity-dependent manner. GluR1 C-terminal deletion (GluR1Δ7) in vitro and in vivo; membrane fractionation; immunofluorescence; dendritic morphometry The Journal of neuroscience Medium 18842882
2009 Two N-terminal SAP97 isoforms (palmitoylated αSAP97 at PSD; L27-containing βSAP97 at perisynaptic regions) differentially localize GluR1-containing AMPARs within subsynaptic subdomains, directly modulating AMPAR dynamics and synaptic function. Live imaging; electrophysiology; isoform-specific overexpression in hippocampal neurons The Journal of neuroscience High 19357261
2009 SAP97 and CASK together are required for retention and trafficking of NMDARs (NR1/NR2B) through a specialized ER subcompartment in hippocampal neurons that bypasses the somatic Golgi and merges with dendritic Golgi outposts; AMPARs use the conventional somatic Golgi pathway. Live imaging of fluorescently-tagged receptors/adaptors in rat hippocampal neurons; RNAi knockdown of SAP97/CASK; subcellular fractionation Nature neuroscience High 19620977
2009 SAP97 forms a tripartite complex with Kv4.2/4.3 channels and CaMKII in cardiomyocytes; SAP97 clustering of Kv4.3 at the plasma membrane enhances Ito current and enables CaMKII-dependent regulation. Kv4 channels lacking the SAL sequence no longer respond to CaMKII inhibitors. Pull-down; co-immunoprecipitation from cardiac myocytes; SAP97 shRNA; adenoviral overexpression; patch clamp Circulation research High 19213956
2009 Inhibiting SAP97-myosin VI interaction (using a dominant-negative myosin VI construct) reduces synapse number, surface AMPAR expression, and prevents activity-dependent AMPAR recruitment to silent synapses in hippocampal neurons. Dominant-negative construct expression; immunofluorescence; whole-cell patch-clamp recording of mEPSCs Journal of neurochemistry Medium 19895665
2009 CaMKII preferentially phosphorylates SAP97 splice variant containing I3 and I5 inserts; AKAP79/150 directly and specifically binds only the I3I5-containing SH3-GK region. CaMKII phosphorylation of this splice variant prevents AKAP79/150 association, thereby relieving AKAP79-dependent down-regulation of GluR1 AMPAR currents. In vitro phosphorylation; GST fusion binding assays; immune complex kinase assay; electrophysiology with active CaMKII infusion The Journal of biological chemistry High 19858198
2010 SAP97 via its PDZ domains interacts specifically with the SIV motif at the C-terminus of cardiac sodium channel Nav1.5 at intercalated discs (while dystrophin-syntrophin complex anchors Nav1.5 at lateral membranes). SAP97 silencing reduces Nav1.5 surface expression and sodium current. Pull-down assays; immunostaining; patch clamp; SAP97 siRNA knockdown in HEK293 and cardiomyocytes; mdx mouse comparison Circulation research High 21164104
2010 Ezrin regulates Dlg1 localization at the immunological synapse, controlling microtubule network organization; ezrin-Dlg1 interaction is required for p38 MAP kinase-dependent NF-AT activation and Erk1/2 downregulation at the immune synapse. Co-immunoprecipitation; RNAi; immunofluorescence; live imaging; TCR signaling assays The EMBO journal Medium 20551903
2010 Conditional SAP97 deletion in mature neurons causes no deficits in glutamatergic transmission or LTP, indicating functional redundancy with other PSD-MAGUKs; overexpression during early development traffics both AMPARs and NMDARs to synapses and rescues AMPAR deficits in PSD-93/-95 double-KO neurons. Conditional knockout; electrophysiology; overexpression in wild-type and double-KO neurons Proceedings of the National Academy of Sciences of the United States of America High 20133708
2010 During wound-induced migration, Cdc42 acts through Dlg1 to regulate dynein interaction with microtubules at the cell front; Dlg1 interacts with dynein via the scaffolding protein GKAP, and together they control microtubule dynamics and centrosome positioning. Co-immunoprecipitation; RNAi knockdown; live imaging; centrosome positioning assay in wounded monolayers The Journal of cell biology High 21041448
2011 PKCα interacts with DLG1/SAP97 via the third PDZ domain of DLG1 and the C-terminal PDZ-binding motif of PKCα; this scaffolding interaction promotes wound healing/cell migration. PKCα phosphorylates DLG1 at Thr-656 in its SH3-Hook region, which serves as a marker of PKCα activity. PDZ domain proteomic array; co-immunoprecipitation; scratch migration assay with PKCα/DLG1 co-depletion; phosphorylation site identification The Journal of biological chemistry Medium 22027822
2011 αSAP97 occludes LTP by enhancing postsynaptic AMPAR levels; βSAP97 blocks LTP by reducing synaptic NMDAR localization while restricting extrasynaptic AMPAR pools. Knockdown of endogenous βSAP97 increases synaptic AMPAR and NMDAR levels. Paired whole-cell recordings from synaptically coupled hippocampal neurons; live imaging; RNAi knockdown; isoform-specific overexpression The Journal of physiology High 21768261
2013 CASK binding to SAP97 via L27 domains stabilizes SAP97 in an 'extended' conformation; unbound SAP97 is in a 'compact' conformation. Compact SAP97 preferentially associates with GluA1-AMPARs; CASK-bound extended SAP97 colocalizes with GluN2B-NMDARs, providing a mechanism for differential receptor sorting. Intramolecular FRET sensors; co-IP; isoform expression in HEK cells and hippocampal neurons; colocalization imaging The Journal of neuroscience High 23864692
2013 DLG1 knockdown decreases surface expression of the glial glutamate transporter EAAT2b (which contains a PDZ ligand) in MDCK cells and astrocytes; DLG1 co-immunoprecipitates with EAAT2b. CaMKII activation disrupts DLG1-EAAT2b interaction and decreases EAAT2b surface expression. Co-immunoprecipitation; shRNA knockdown; surface biotinylation assay; CaMKII pharmacological activation The Journal of neuroscience Medium 25834051
2013 DLG1 is an anchor for the MARCH2 E3 ubiquitin ligase at cell-cell contact sites via PDZ domain interaction; MARCH2 promotes ubiquitination of DLG1 in vivo. Tandem affinity purification + mass spectrometry; co-immunoprecipitation; in vivo ubiquitination assay; immunofluorescence with PDZ-motif deletion Cellular signalling Medium 17980554
2013 SAP97 governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes in hippocampal neurons; this process requires PKC phosphorylation of SAP97's SH3 domain, which modulates SAP97-ADAM10 association. This mechanism is altered in Alzheimer's disease brains. Co-immunoprecipitation; phosphosite mapping; PKC inhibitor/activator treatment; siRNA knockdown; confocal imaging Cell death & disease Medium 25429624
2014 Dlg1 is localized at the basolateral cell cortex during mitosis and directly interacts with LGN, promoting cortical localization of the LGN complex to control planar spindle orientation in the chick neuroepithelium and human cells. Live imaging of spindle movements; RNAi knockdown; co-immunoprecipitation; overexpression on adhesive micropatterns The Journal of cell biology High 25202028
2014 Cardiac-specific SAP97 ablation in mice decreases IK1, Ito, and IKur potassium currents and prolongs action potential duration without affecting INa, confirming SAP97's role in regulating potassium channel function in vivo. Cardiac-specific Cre-lox knockout; patch clamp; ECG; immunostaining Heart rhythm High 25447080
2016 Pten recruits Dlg1-Eg5 complexes to pre-mitotic centrosomes via its PDZ-binding domain; Eg5 phosphorylation by Nek9-Nek6 and Cdk1 kinases is required for docking onto Pten-Dlg1. Dlg1 ablation impairs Eg5 loading onto centrosomes and spindle pole motility, causing asymmetric spindles and chromosome missegregation. Co-immunoprecipitation; mouse genetic models (PDZ-BD deletion, Dlg1 ablation); centrosome fractionation; live imaging of spindle poles; aneuploidy assays Nature cell biology High 27240320
2016 In Schwann cells, Kif13b kinesin promotes p38γ MAPK-mediated phosphorylation and ubiquitination of Dlg1, downregulating Dlg1 and the PI3K/AKT pathway. In oligodendrocytes, Kif13b negatively regulates Dlg1 stability; Dlg1 in that context enhances AKT activation and myelination. Kif13b conditional knockout mice; immunoprecipitation; phosphorylation and ubiquitination assays; AKT pathway analysis PLoS biology Medium 27070899
2019 Vascular endothelial cell-specific loss of Dlg1 impairs β-catenin (canonical Wnt) signaling in the retina. Dlg1 transfection in reporter cells with Dlg1 inactivation enhances β-catenin signaling ~4-fold; the retinal vascular phenotype is rescued by stabilizing β-catenin in ECs. EC-specific Cre-lox knockout; genetic epistasis with β-catenin signaling components; CRISPR/Cas9 inactivation in reporter cells; β-catenin stabilization rescue eLife High 31066677
2019 SGEF forms a ternary complex with Scribble and Dlg1; SGEF targets to apical junctions in a Scribble-dependent manner and regulates actomyosin contractility and barrier function through RhoG activation coordinated by the Scribble-Dlg1 scaffold. Co-immunoprecipitation; RNAi knockdown; 3D cyst assay; immunofluorescence; Scribble-dependent targeting assay The Journal of cell biology Medium 31248911
2020 SAP97 maintains cardiac β1AR signaling integrity by scaffolding β1AR; GRK5 promotes agonist-induced dissociation of SAP97 from β1AR. Loss of SAP97 shifts β1AR toward arrestin2-CaMKII association and activates Epac-dependent CaMKII, causing cardiac remodeling. Cardiac-specific SAP97 deletion; co-immunoprecipitation; CaMKII activity assays; cardiac function measurements; GRK5 deletion epistasis Circulation research High 32507058

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit. The Journal of biological chemistry 358 9677374
1994 Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1. Proceedings of the National Academy of Sciences of the United States of America 342 7937897
1995 Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 340 7891172
1997 Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proceedings of the National Academy of Sciences of the United States of America 316 9192623
2005 Cdc42 and Par6-PKCzeta regulate the spatially localized association of Dlg1 and APC to control cell polarization. The Journal of cell biology 248 16157700
2005 p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP. The EMBO journal 206 15729360
2004 Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Neuron 206 15504326
2010 SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes. Circulation research 203 21164104
2006 Alternative N-terminal domains of PSD-95 and SAP97 govern activity-dependent regulation of synaptic AMPA receptor function. Neuron 203 16815335
2009 SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway. Nature neuroscience 181 19620977
2000 The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene 158 10656683
2000 PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+) channel surface expression and clustering. The Journal of cell biology 157 10629225
2004 A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. The Journal of biological chemistry 130 14960569
1998 Subcellular targeting and cytoskeletal attachment of SAP97 to the epithelial lateral membrane. Journal of cell science 125 9683631
2002 A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia. Molecular and cellular biology 119 11865057
2004 Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma. Cancer research 112 14871824
1997 DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95. Genes to cells : devoted to molecular & cellular mechanisms 110 9286858
1996 Two independent domains of hDlg are sufficient for subcellular targeting: the PDZ1-2 conformational unit and an alternatively spliced domain. The Journal of cell biology 107 8922391
2001 DLG-1 is a MAGUK similar to SAP97 and is required for adherens junction formation. Molecular biology of the cell 106 11694581
2001 Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97. Journal of cell science 104 11181181
1999 Tax oncoprotein of HTLV-1 binds to the human homologue of Drosophila discs large tumor suppressor protein, hDLG, and perturbs its function in cell growth control. Oncogene 104 10557085
2002 Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia. Journal of neurochemistry 101 12421351
2006 Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. Nature immunology 99 17187070
1998 E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton. Journal of cell science 99 9512503
2005 Dlgh1 coordinates actin polymerization, synaptic T cell receptor and lipid raft aggregation, and effector function in T cells. The Journal of experimental medicine 97 15699074
2010 The role of SAP97 in synaptic glutamate receptor dynamics. Proceedings of the National Academy of Sciences of the United States of America 96 20133708
2010 Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse. The EMBO journal 95 20551903
2000 hCASK and hDlg associate in epithelia, and their src homology 3 and guanylate kinase domains participate in both intramolecular and intermolecular interactions. The Journal of biological chemistry 94 10993877
2009 Synaptic SAP97 isoforms regulate AMPA receptor dynamics and access to presynaptic glutamate. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 19357261
2009 Dlg1, Sec8, and Mtmr2 regulate membrane homeostasis in Schwann cell myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 19587293
2004 Discs large (Dlg1) complexes in lymphocyte activation. The Journal of cell biology 90 15263016
2003 CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction. The Journal of biological chemistry 88 12933808
2000 SAP97 concentrates at the postsynaptic density in cerebral cortex. The European journal of neuroscience 86 11029631
1997 Functional expression of rat synapse-associated proteins SAP97 and SAP102 in Drosophila dlg-1 mutants: effects on tumor suppression and synaptic bouton structure. Mechanisms of development 86 9152008
1999 Differential interaction of the tSXV motifs of the NR1 and NR2A NMDA receptor subunits with PSD-95 and SAP97. The European journal of neuroscience 72 10336672
2009 Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes. Circulation research 71 19213956
2010 Dlg1 binds GKAP to control dynein association with microtubules, centrosome positioning, and cell polarity. The Journal of cell biology 69 21041448
2007 Abnormal development of urogenital organs in Dlgh1-deficient mice. Development (Cambridge, England) 69 17435047
2001 The distribution and function of alternatively spliced insertions in hDlg. The Journal of biological chemistry 66 11723125
2006 Assembly of an SAP97-AKAP79-cAMP-dependent protein kinase scaffold at the type 1 PSD-95/DLG/ZO1 motif of the human beta(1)-adrenergic receptor generates a receptosome involved in receptor recycling and networking. The Journal of biological chemistry 65 17170109
2006 Dual role of CaMKII-dependent SAP97 phosphorylation in mediating trafficking and insertion of NMDA receptor subunit NR2A. Journal of neurochemistry 64 17156128
2005 Subcellular redistribution of the synapse-associated proteins PSD-95 and SAP97 in animal models of Parkinson's disease and L-DOPA-induced dyskinesia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 64 15703272
2007 The stardust family protein MPP7 forms a tripartite complex with LIN7 and DLG1 that regulates the stability and localization of DLG1 to cell junctions. The Journal of biological chemistry 63 17237226
2001 Molecular mechanisms regulating the differential association of kainate receptor subunits with SAP90/PSD-95 and SAP97. The Journal of biological chemistry 63 11279111
2014 SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation. Cell death & disease 56 25429624
2014 Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN. The Journal of cell biology 54 25202028
2008 GluR1 controls dendrite growth through its binding partner, SAP97. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 18842882
2010 SAP97-mediated local trafficking is altered in Alzheimer disease patients' hippocampus. Neurobiology of aging 52 20980075
2007 Differential neuronal and glial expression of GluR1 AMPA receptor subunit and the scaffolding proteins SAP97 and 4.1N during rat cerebellar development. The Journal of comparative neurology 52 17335044
2016 Pten regulates spindle pole movement through Dlg1-mediated recruitment of Eg5 to centrosomes. Nature cell biology 51 27240320
2011 Protein kinase Cα promotes cell migration through a PDZ-dependent interaction with its novel substrate discs large homolog 1 (DLG1). The Journal of biological chemistry 51 22027822
2004 The notch ligand Delta1 recruits Dlg1 at cell-cell contacts and regulates cell migration. The Journal of biological chemistry 49 15485825
2018 lncRNA DLG1-AS1 Promotes Cell Proliferation by Competitively Binding with miR-107 and Up-Regulating ZHX1 Expression in Cervical Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 30231238
2001 SAP97 interacts with Kv1.5 in heterologous expression systems. American journal of physiology. Heart and circulatory physiology 46 11709425
2001 Proteasome-mediated regulation of the hDlg tumour suppressor protein. Journal of cell science 46 11739660
2009 Ca2+/calmodulin-dependent protein kinase II binds to and phosphorylates a specific SAP97 splice variant to disrupt association with AKAP79/150 and modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPAR) activity. The Journal of biological chemistry 45 19858198
2011 SAP97 directs NMDA receptor spine targeting and synaptic plasticity. The Journal of physiology 44 21768261
2002 Expression, regulation and role of the MAGUK protein SAP-97 in human atrial myocardium. Cardiovascular research 44 12445884
2013 CASK regulates SAP97 conformation and its interactions with AMPA and NMDA receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 23864692
2008 DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 18171947
2013 The anchoring protein SAP97 influences the trafficking and localisation of multiple membrane channels. Biochimica et biophysica acta 42 23535319
2007 SAP97 directs the localization of Kv4.2 to spines in hippocampal neurons: regulation by CaMKII. The Journal of biological chemistry 42 17635915
2005 Interaction between SAP97 and PSD-95, two Maguk proteins involved in synaptic trafficking of AMPA receptors. The Journal of biological chemistry 42 16332687
1998 Functional analysis of the guanylate kinase-like domain in the synapse-associated protein SAP97. European journal of biochemistry 42 9523702
2009 Disruption of the interaction between myosin VI and SAP97 is associated with a reduction in the number of AMPARs at hippocampal synapses. Journal of neurochemistry 41 19895665
2008 The anchoring protein SAP97 retains Kv1.5 channels in the plasma membrane of cardiac myocytes. American journal of physiology. Heart and circulatory physiology 41 18245566
2008 An association analysis of synapse-associated protein 97 (SAP97) gene in schizophrenia. Journal of neural transmission (Vienna, Austria : 1996) 41 18665322
2007 Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein. Biochemistry 40 17713926
2015 Differential regulation of two isoforms of the glial glutamate transporter EAAT2 by DLG1 and CaMKII. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 25834051
2014 Cardiac-specific ablation of synapse-associated protein SAP97 in mice decreases potassium currents but not sodium current. Heart rhythm 39 25447080
2012 Further evidence for a male-selective genetic association of synapse-associated protein 97 (SAP97) gene with schizophrenia. Behavioral and brain functions : BBF 38 22225629
2012 A functional network of the tumor suppressors APC, hDlg, and PTEN, that relies on recognition of specific PDZ-domains. Journal of cellular biochemistry 38 22434720
2003 Identification of SAP97 as an intracellular binding partner of TACE. Journal of cell science 38 12668732
2016 Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold. PLoS biology 36 27070899
2001 Characterization of a novel human cell-cycle-regulated homologue of Drosophila dlg1. Genomics 36 11543626
2013 SHIP2 regulates epithelial cell polarity through its lipid product, which binds to Dlg1, a pathway subverted by hepatitis C virus core protein. Molecular biology of the cell 35 23699395
2003 Different isoforms of synapse-associated protein, SAP97, are expressed in the heart and have distinct effects on the voltage-gated K+ channel Kv1.5. The Journal of biological chemistry 35 12970345
2007 DLGH1 is a negative regulator of T-lymphocyte proliferation. Molecular and cellular biology 34 17724087
2013 Emerging role of the scaffolding protein Dlg1 in vesicle trafficking. Traffic (Copenhagen, Denmark) 33 23829493
2019 Dlg1 activates beta-catenin signaling to regulate retinal angiogenesis and the blood-retina and blood-brain barriers. eLife 31 31066677
2019 SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility. The Journal of cell biology 30 31248911
2007 DLG1 is an anchor for the E3 ligase MARCH2 at sites of cell-cell contact. Cellular signalling 30 17980554
2018 Circ-DLG1 promotes the proliferation of esophageal squamous cell carcinoma. OncoTargets and therapy 29 30349305
2011 Mutation screening of the 3q29 microdeletion syndrome candidate genes DLG1 and PAK2 in schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 28 21850710
2000 The hDLG-associated protein DAP interacts with dynein light chain and neuronal nitric oxide synthase. Genes to cells : devoted to molecular & cellular mechanisms 28 11122378
2019 Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology. Biological chemistry 27 30517074
2012 A functional interaction between the MAGUK protein hDlg and the gap junction protein connexin 43 in cervical tumour cells. The Biochemical journal 27 22657348
2002 Synaptic glutamate receptor clustering in mice lacking the SH3 and GK domains of SAP97. The European journal of neuroscience 27 12405965
2013 Scaffolding proteins DLG1 and CASK cooperate to maintain the nephron progenitor population during kidney development. Journal of the American Society of Nephrology : JASN 26 23661808
2021 Dlg1 Knockout Inhibits Microglial Activation and Alleviates Lipopolysaccharide-Induced Depression-Like Behavior in Mice. Neuroscience bulletin 25 34490521
2013 Role of SAP97 protein in the regulation of corticotropin-releasing factor receptor 1 endocytosis and extracellular signal-regulated kinase 1/2 signaling. The Journal of biological chemistry 25 23576434
2006 Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein. Retrovirology 25 17042961
2022 The SF3B1R625H mutation promotes prolactinoma tumor progression through aberrant splicing of DLG1. Journal of experimental & clinical cancer research : CR 24 35039052
2021 Whole-Exome Sequencing Identified DLG1 as a Candidate Gene for Familial Exudative Vitreoretinopathy. Genetic testing and molecular biomarkers 24 33945310
2020 GRK5 Controls SAP97-Dependent Cardiotoxic β1 Adrenergic Receptor-CaMKII Signaling in Heart Failure. Circulation research 23 32507058
2015 A Critical Role for the GluA1 Accessory Protein, SAP97, in Cocaine Seeking. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 23 26149358
2012 Characterization of in vivo Dlg1 deletion on T cell development and function. PloS one 23 23028902
2011 Transcriptional activation of the anchoring protein SAP97 by heat shock factor (HSF)-1 stabilizes K(v) 1.5 channels in HL-1 cells. British journal of pharmacology 23 21232033
2008 Regulation of the hDlg/hScrib/Hugl-1 tumour suppressor complex. Experimental cell research 23 18793635
2007 Changes in localization of human discs large (hDlg) during keratinocyte differentiation are [corrected] associated with expression of alternatively spliced hDlg variants. Experimental cell research 23 17574238

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