Affinage

DLG2

Disks large homolog 2 · UniProt Q15700

Length
870 aa
Mass
97.6 kDa
Annotated
2026-06-09
64 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLG2 (PSD-93/Chapsyn-110) is a membrane-associated guanylate kinase (MAGUK) scaffold that organizes receptor and ion-channel signaling complexes at the postsynaptic density of excitatory synapses, where it localizes to asymmetric axo-spinous junctions and forms part of the PSD backbone scaffold (PMID:11309840, PMID:18392731). Through its PDZ domains it directly binds and clusters NMDA receptor subunits and Shaker-type K+ channels, heteromultimerizing with PSD-95 into a multimeric scaffold (PMID:8755482); its PDZ1/2 modules preferentially engage GluN2B over GluD2 C-terminal tails (PMID:23519667), and an alternatively spliced isoform clusters the inward-rectifier Kir2.1 while suppressing its internalization (PMID:15304517). DLG2 also stabilizes neuronal nicotinic acetylcholine receptors at cholinergic synapses (PMID:14724236). Its scaffolding output is gated by phosphorylation: Fyn phosphorylates DLG2 at Tyr-384 on a palmitoylation-anchored substrate, ERK2 at Ser-323, and Rho-kinase/ROCK at Thr612 to strengthen its binding to PSD-95 and NMDARs, while Src phosphorylation at multiple tyrosines reduces client affinity and modulates condensate behavior (PMID:13129934, PMID:22618309, PMID:36613848, PMID:41562278). Functionally, DLG2 is required for hippocampal LTP and homeostatic scaling up and organizes NMDA receptor signaling complexes distinct from those of PSD-95, including coupling NMDAR activity to Fyn-mediated GluN2B phosphorylation and SynGAP ubiquitination in excitotoxic signaling (PMID:18936077, PMID:20554866, PMID:21543610, PMID:24787897, PMID:32130656). DLG2 governs potassium-channel-dependent dendritic integration that gates associative plasticity (PMID:35115661), is required for striatum-specific excitatory synapse maintenance and for cortical neuronal differentiation (PMID:32164788, PMID:35031607, PMID:35966008), and acts as a tumor suppressor in osteosarcoma and neuroblastoma by controlling proliferation, differentiation, the DNA damage response, and apoptotic signaling (PMID:30093633, PMID:32966799, PMID:35217496). A DLG2 F900V variant impairing the PSD-93–Fyn interaction is associated with autosomal dominant delayed puberty (PMID:32341572).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established DLG2 as a PDZ-domain MAGUK that physically clusters ionotropic receptors and channels, defining its core scaffolding identity at the synapse.

    Evidence Co-IP, yeast two-hybrid, and heterologous clustering of NMDA receptors and Shaker K+ channels, with heteromultimerization to PSD-95

    PMID:8755482

    Open questions at the time
    • Did not establish in vivo synaptic requirement
    • Affinity and subunit selectivity among receptor partners not quantified
  2. 2001 High

    Localized DLG2 ultrastructurally to postsynaptic densities of asymmetric synapses and showed a single-MAGUK synapse type tolerates its loss, framing both a synaptic anchoring role and functional redundancy.

    Evidence EM immunogold mapping in visual cortex; knockout mouse analysis of cerebellar parallel-fiber synapses

    PMID:11309840 PMID:11312293

    Open questions at the time
    • Did not resolve which synapse types strictly require DLG2
    • Presynaptic and cytoplasmic pools not functionally assigned
  3. 2003 Medium

    Identified DLG2 as a tyrosine kinase substrate, linking its membrane anchoring and phosphorylation by Fyn (Tyr-384) to NMDA receptor signaling regulation.

    Evidence In vitro kinase assay, mutagenesis, Fyn-KO brain comparison, and Csk Co-IP; antisense knockdown in spinal pain models; KO of NMDAR-nNOS complex assembly

    PMID:13129934 PMID:14581127 PMID:15296832

    Open questions at the time
    • Functional consequence of Tyr-384 phosphorylation in vivo not isolated
    • nNOS coupling tested in single contexts
  4. 2004 High

    Broadened the DLG2 client repertoire beyond NMDARs to nAChRs and Kir2.1 channels, showing it stabilizes diverse postsynaptic surface receptors via isoform-specific PDZ interactions.

    Evidence Co-IP and KO denervation phenotype for nAChRs; yeast two-hybrid, in vitro binding, and surface clustering for Kir2.1 (PSD-93delta)

    PMID:14724236 PMID:15304517

    Open questions at the time
    • Isoform-specific expression patterns across neuron types not mapped
    • Mechanism of internalization suppression unresolved
  5. 2008 High

    Demonstrated that DLG2 and PSD-95 have divergent, non-interchangeable roles in plasticity and that DLG2 organizes distinct NMDA receptor signaling complexes.

    Evidence KO mouse electrophysiology showing LTP deficits without LTD changes; quantitative EM immunogold mapping of isolated PSDs

    PMID:18392731 PMID:18936077

    Open questions at the time
    • Molecular basis of opposing PSD-93 vs PSD-95 LTP roles not defined
    • Complex composition differences not biochemically resolved
  6. 2010 High

    Distinguished DLG2 from PSD-95 in membrane microdomain organization, showing PSD-95 (not DLG2) targets NR2A complexes to lipid rafts.

    Evidence TAP-tag knockin mice, lipid raft fractionation, and PSD-93/PSD-95 KO comparison

    PMID:20554866

    Open questions at the time
    • Which subunit complexes DLG2 selectively organizes left open
    • Raft-independent DLG2 functions not characterized
  7. 2011 Medium

    Showed DLG2 is functionally required for homeostatic scaling up through interactions distinct from those PSD-95 uses for scaling down, despite not being activity-regulated itself.

    Evidence Lentiviral knockdown/overexpression in cortical neurons with mEPSC recording

    PMID:21543610

    Open questions at the time
    • The specific scaling-up interactions not molecularly identified
    • Age dependence mechanism unexplained
  8. 2012 Medium

    Added ERK2 as a second kinase regulating DLG2, mapping phosphorylation to Ser-323 and embedding DLG2 in synaptic signaling cascades.

    Evidence In vitro protein interaction and kinase assays, mutagenesis, and striatal synaptosomal Co-IP

    PMID:22618309

    Open questions at the time
    • Functional consequence of Ser-323 phosphorylation untested
    • Single-lab in vitro identification
  9. 2013 High

    Resolved structurally that DLG2 PDZ1/2 preferentially bind GluN2B over GluD2, providing atomic-level basis for receptor selectivity.

    Evidence X-ray crystallography of PDZ1-GluD2 peptide complex and fluorescence polarization binding measurements

    PMID:23519667

    Open questions at the time
    • Selectivity not validated in cells
    • Full-length scaffold avidity effects not addressed
  10. 2014 High

    Placed DLG2 upstream of Fyn-mediated GluN2B Tyr1472 phosphorylation in excitotoxic signaling, defining a mechanistic link between scaffolding and ischemic injury.

    Evidence KO mouse MCAO model, phospho-Western, Co-IP, and PP2 pharmacological epistasis

    PMID:24787897

    Open questions at the time
    • Therapeutic targeting feasibility not addressed here
    • Whether effect is purely scaffold-dependent unresolved
  11. 2020 Medium

    Extended DLG2 mechanism to ubiquitin-dependent degradation of SynGAP downstream of NMDAR activation, with a defined interaction interface and a protective interfering peptide.

    Evidence Co-IP, domain mapping (SynGAP 670-685), proteasome inhibitor rescue, KO epistasis, and MCAO peptide intervention

    PMID:32130656

    Open questions at the time
    • E3 ligase mediating ubiquitination not identified
    • Direct DLG2 catalytic involvement vs adaptor role unclear
  12. 2020 High

    Established region-specific in vivo synaptic requirements for DLG2 in the striatum and revealed non-neuronal roles in beta-cell insulin secretion and a disease-associated Fyn-binding variant.

    Evidence Dlg2 KO mouse striatal patch-clamp; MIN6 knockdown insulin secretion assay; exome sequencing and Co-IP of F900V variant

    PMID:32164788 PMID:32341572 PMID:32356104

    Open questions at the time
    • Mechanism of insulin-secretion role uncharacterized
    • F900V causality not validated in vivo
  13. 2020 High

    Defined DLG2 as a tumor suppressor controlling proliferation and differentiation, downstream of oncogenic ALK-ERK-SP1 repression in neuroblastoma and through L27-mediated LIN7A binding.

    Evidence DLG2-deficient osteosarcoma cell lines and conditional KO mice (2018); neuroblastoma re-expression with ALK-inhibitor/SP1 epistasis; isoform-specific LIN7A Co-IP

    PMID:30093633 PMID:32966799 PMID:33726762

    Open questions at the time
    • Molecular mechanism coupling DLG2 to cell-cycle control incomplete
    • Isoform-dependent tumor-suppressive interactions not fully mapped
  14. 2022 High

    Identified ROCK/Thr612 phosphorylation as a positive regulator of DLG2 scaffolding and discovered that DLG2 regulates potassium-channel-dependent dendritic integration gating associative plasticity.

    Evidence In vitro kinase assay, phospho-antibody, LC-MS/MS interactome, chemical-LTP (Thr612); Dlg2+/- rat patch-clamp with K+-channel and M1 pharmacological rescue and modeling

    PMID:35115661 PMID:36613848

    Open questions at the time
    • Which K+ channels DLG2 regulates not molecularly identified
    • Link between phosphorylation and dendritic integration not integrated
  15. 2022 High

    Showed DLG2 is required for cortical neuronal differentiation and striatum-specific synapse formation, and extended its tumor-suppressor mechanism to the DNA damage response and inflammasome/AKT-S6 signaling.

    Evidence DLG2 KO hESC cortical differentiation with transcriptomics and electrophysiology; Dlg2 KO striatal EM/mEPSC; comet/gammaH2AX assays with Drosophila model; colon cancer OE/KD cytokine and signaling readouts

    PMID:35031607 PMID:35217496 PMID:35499706 PMID:35966008

    Open questions at the time
    • Transcriptional mechanism in neurogenesis not defined
    • Connection between synaptic scaffold and DNA-damage roles unexplained
  16. 2026 Medium

    Provided biophysical mechanism distinguishing DLG2 from PSD-95: Src tyrosine phosphorylation reduces DLG2 client affinity, inhibits supercomplex formation, and uniquely alters its biomolecular condensation.

    Evidence In vitro Src kinase assay, fluorescence polarization, SAXS, single-molecule FRET, and scaffolding/condensation assays

    PMID:41562278

    Open questions at the time
    • No in-cell validation of condensate effects
    • Physiological phospho-site occupancy unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DLG2's synaptic scaffolding mechanism mechanistically connects to its tumor-suppressor and DNA-damage roles, and what E3 ligase and signaling intermediates execute these non-synaptic functions, remains unresolved.
  • No unified mechanism linking synaptic scaffold and proliferation control
  • SynGAP-degrading E3 ligase unidentified
  • Cross-tissue mechanistic basis (beta cell, tumor) uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 1
Partners
CSKCX3CL1ERK2FYNKIR2.1LIN7APSD-95SYNGAP
Complex memberships
postsynaptic density

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Chapsyn-110/DLG2 is a MAGUK protein that directly binds NMDA receptor subunits and Shaker K+ channel subunits via its PDZ domains, mediates clustering of both NMDA receptors and K+ channels in heterologous cells, and heteromultimerizes with PSD-95 to form a multimeric postsynaptic scaffold. Co-immunoprecipitation, heterologous cell clustering assay, yeast two-hybrid, subcellular fractionation Neuron High 8755482
2001 Electron microscopic immunocytochemistry demonstrated that PSD-93/DLG2 localizes to postsynaptic densities of asymmetric axo-spinous synapses in rat visual cortex, as well as along presynaptic membranes and in axonal/dendritic cytoplasm, suggesting dual roles in maintaining receptors at synapses and regulating receptor shuttling. Electron microscopic immunocytochemistry with quantitative immunogold labeling Synapse High 11309840
2001 PSD-93 knockout mice show no structural or functional abnormality in cerebellar parallel fiber synapses despite PSD-93 being the only MAGUK expressed in Purkinje neurons, indicating PSD-93 is not essential for development of certain central synapses but may participate in specialized synaptic signaling. Targeted gene disruption (knockout mouse), light and electron microscopy, electrophysiology, behavioral testing The Journal of neuroscience High 11312293
2003 PSD-93/DLG2 is a substrate for the Src family tyrosine kinase Fyn; Fyn phosphorylates PSD-93 in vitro and in vivo at Tyr-384, an N-terminal palmitoylation signal is required for membrane anchoring where Fyn is localized, and tyrosine-phosphorylated PSD-93 binds Csk (a negative regulator of Src family kinases). Immunopurification of NMDA receptor complex, microsequencing, in vitro kinase assay with recombinant proteins, site-directed mutagenesis, Fyn-deficient mouse brain comparison, Co-IP from brain lysate The Journal of biological chemistry High 13129934
2003 Knockdown of spinal cord PSD-93/DLG2 by intrathecal antisense oligodeoxynucleotide significantly attenuates thermal and mechanical hyperalgesia in CFA-induced inflammatory pain and peripheral nerve injury-induced neuropathic pain, without affecting acute nociception or locomotion, indicating PSD-93 is required for central sensitization mechanisms downstream of NMDAR activation. Intrathecal antisense oligodeoxynucleotide knockdown in rat, behavioral pain assays (paw withdrawal thresholds), Western blot confirmation of knockdown Pain Medium 14581127
2003 In neonatal hypoxia-ischemia, PSD-93 deletion does not provide neuroprotection; PSD-95 compensates by still interacting with NR2B and nNOS in PSD-93 KO mice, and PSD-95 expression is upregulated after HI in KO pups, demonstrating functional redundancy between MAGUKs at baseline. PSD-93 KO mouse model, neonatal HI model, Western blot, co-immunoprecipitation, brain injury scoring Stroke Medium 14605317
2004 PSD-93/DLG2 colocalizes and co-immunoprecipitates with NMDA receptors and neuronal nitric oxide synthase in cultured cortical neurons; PSD-93 gene disruption prevents NMDA receptor-nNOS complex formation, attenuates PAF-induced cGMP elevation, and significantly reduces PAF-triggered NMDA receptor-nitric oxide signaling-dependent neurotoxicity. Co-immunoprecipitation, targeted gene disruption (KO neurons), cGMP measurement, neurotoxicity assay Experimental neurology Medium 15296832
2004 Novel splice forms of PSD-93/DLG2 are expressed in mouse superior cervical ganglion (SCG); PSD-93 co-localizes with and co-immunoprecipitates neuronal nicotinic acetylcholine receptors (nAChRs) at cholinergic synapses, and PSD-93 KO mice show accelerated disassembly of nAChR synaptic clusters after denervation, establishing PSD-93 as a stabilizing scaffold at neuronal cholinergic postsynaptic densities. Immunostaining, subcellular fractionation, co-immunoprecipitation, PSD-93 KO mouse denervation model The Journal of neuroscience High 14724236
2004 An alternatively spliced isoform of PSD-93 (PSD-93δ) directly interacts with the inwardly rectifying K+ channel Kir2.1 via a type I PDZ recognition motif at the Kir2.1 C-terminus; co-expression of Kir2.1 and PSD-93δ causes cell surface clustering of Kir2.1 and suppresses channel internalization without affecting channel kinetics. Yeast two-hybrid screening, in vitro binding assay, co-immunoprecipitation from rat spinal cord, heterologous cell expression with surface clustering assay The Journal of biological chemistry High 15304517
2008 PSD-93 KO mice exhibit normal AMPA and NMDA receptor-mediated synaptic transmission but show deficits in LTP induction without affecting LTD, demonstrating that PSD-93 and PSD-95 have opposing roles in LTP in hippocampal CA1 and likely organize distinct NMDA receptor signaling complexes. PSD-93 KO and PSD-95 KO mouse electrophysiology, field recordings in hippocampal slices, multiple LTP/LTD induction protocols The Journal of physiology High 18936077
2008 PSD-93 is homogeneously distributed throughout isolated postsynaptic densities (similar distribution to PSD-95), consistent with PSD-93 forming part of a backbone scaffold that stabilizes binding partners within the PSD. EM immunogold labeling and quantitative mapping of isolated PSDs on glass coverslips Brain cell biology Medium 18392731
2010 In vivo, PSD-95 (not PSD-93) is the critical scaffold for localizing NR2A-containing NMDA receptor complexes to lipid rafts; PSD-93 KO does not alter NR2A raft localization, while PSD-95 KO reduces NR2A association with rafts, indicating differential roles in organizing NMDA receptor signaling complexes across membrane microdomains. Tandem affinity purification (TAP-tag knockin mice), lipid raft isolation, PSD-95 and PSD-93 KO mice, immunoblot The Journal of neuroscience High 20554866
2011 PSD-93 is required for scaling up of synaptic strength (homeostatic synaptic potentiation) in a manner that depends on neuronal age and can substitute for PSD-95 in this process; synaptic PSD-93 abundance is not bidirectionally regulated by activity (unlike PSD-95 and SAP102), yet it is functionally necessary for scaling up via distinct protein-protein interactions from those used by PSD-95 in scaling down. Lentiviral shRNA knockdown, overexpression in cortical neurons, mEPSC recording, immunofluorescence quantification The Journal of neuroscience Medium 21543610
2012 PSD-93 is a direct substrate of ERK2; purified ERK2 physically interacts with an N-terminal region of PSD-93 and phosphorylates it at Ser-323 in vitro; native ERK co-associates with PSD-93 in striatal synaptosomal fractions and immunoprecipitated PSD-93 shows basal ERK-sensitive phosphorylation in vivo. In vitro protein-protein interaction assay with purified proteins, in vitro kinase assay, site-directed mutagenesis, synaptosomal co-immunoprecipitation Brain research Medium 22618309
2013 Crystal structure and fluorescence polarization spectroscopy of PSD-93 PDZ1 with a GluD2 C-terminal peptide (GTSI) revealed two different binding modes of weak affinity; the two N-terminal PDZ domains of PSD-93 show no appreciable binding to a GluD2-derived octapeptide but micromolar affinity for a GluN2B-derived C-terminal octapeptide, indicating PDZ1/2 of PSD-93 preferentially engage GluN2B over GluD2. X-ray crystallography, fluorescence polarization spectroscopy (in vitro binding assay) Acta crystallographica Section D High 23519667
2014 PSD-93 deletion reduces ischemic infarct volume and neurological deficits in adult mice after MCAO; PSD-93 KO decreased Fyn-mediated phosphorylation of NR2B at Tyr1472 and reduced NR2B-Fyn interaction after ischemia, and prevented induction of ischemic LTP; Src family inhibitor PP2 phenocopied the KO effect, placing PSD-93 upstream of Fyn-NR2B phosphorylation in excitotoxic signaling. PSD-93 KO mouse MCAO model, electrophysiology (ischemic LTP), phospho-Western blot, Co-IP, pharmacological inhibition with AP-5 and PP2 Neurobiology of disease High 24787897
2017 PSD-93 overexpression in APP/PS1 mice increases SSTR4 membrane levels (linked to reduced ubiquitination) and neprilysin expression, reduces amyloid plaque load and Aβ levels, and improves spatial memory; PSD-93 co-immunoprecipitates with SSTR4, indicating PSD-93 stabilizes SSTR4 at the membrane to promote Aβ catabolism. Lentivirus-mediated overexpression, Co-IP, Morris water maze, LTP recording, ELISA, immunohistochemistry Journal of Alzheimer's disease Medium 28697571
2018 DLG2/PSD-93 has a regulatory role in cell division, migration, and tumorigenesis; DLG2-deficient osteosarcoma cell lines show increased cell proliferation and migration, and osteoblast-specific Dlg2 deletion in a mouse model accelerates osteosarcoma development, establishing DLG2 as a tumor suppressor. DLG2-deficient human and canine OS cell lines (functional assays: migration, proliferation, tumorigenesis), osteoblast-specific conditional KO mouse model Oncogene High 30093633
2020 PSD-93 directly interacts with SynGAP (binding region: 670-685 aa of SynGAP) and mediates SynGAP ubiquitination and proteasomal degradation following ischemia-reperfusion; in PSD-93 KO mice, NMDAR inhibition or proteasome inhibition did not further alter SynGAP levels, placing PSD-93 downstream of NMDAR activation and upstream of SynGAP ubiquitination; a fusion peptide Tat-SynGAP(670-685aa) inhibiting this interaction reduced ischemic brain damage. Co-IP, domain-mapping peptide competition, proteasome inhibitor (MG-132) rescue, PSD-93 KO mice, MCAO model, NMDAR inhibitor (MK801) Translational stroke research Medium 32130656
2020 Dlg2 KO mice (exon 14 deletion) show reduced excitatory synaptic input (decreased frequency of spontaneous EPSCs) in dorsolateral striatum without changes in inhibitory currents, establishing DLG2 as required for maintenance of excitatory synaptic transmission in the striatum. Dlg2 KO mouse, whole-cell patch-clamp electrophysiology in dorsolateral striatum, behavioral battery, in situ hybridization Molecular autism High 32164788
2020 DLG2 restoration in neuroblastoma cells spontaneously drives differentiation; oncogenic ALK-ERK1/2-SP1 signaling represses DLG2 expression to maintain an undifferentiated state, placing DLG2 downstream of ALK-ERK-SP1 in the differentiation pathway. DLG2 re-expression in neuroblastoma cell lines, morphological and marker differentiation analysis, ALK inhibitor treatment, SP1 overexpression/knockdown Cell reports Medium 32966799
2020 Knockdown of Dlg2 in MIN6 pancreatic beta cells impairs glucose-stimulated and non-glucose-stimulated insulin secretion, indicating DLG2 is functionally required for insulin secretion in beta cells. RNA interference knockdown in MIN6 cells, glucose-stimulated insulin secretion assay, in vivo congenic mouse mapping Diabetologia Medium 32356104
2021 PSD-93 interacts with CX3CL1 (binding sites: aa 420-535 of PSD-93 and aa 357-395 of CX3CL1) following ischemia-reperfusion; a peptide blocking this interaction (Tat-CX3CL1 357-395aa) inhibits pro-inflammatory cytokine expression (IL-1β, TNF-α) and reduces ischemic neuronal death, placing PSD-93 upstream of microglial activation via CX3CL1 in ischemic neuroinflammation. MCAO model, Co-IP, domain-mapping peptide competition, cytokine assay, infarct volume measurement Journal of neurochemistry Medium 33599284
2021 DLG2 isoform 7 (containing the L27 domain) binds LIN7A, and increased DLG2-isoform 7 expression upregulates LIN7A, reduces neuroblastoma cell proliferation and viability, and increases BAX/BCL2 ratio; the L27 domain-lacking isoform 2 does not bind LIN7A and its expression is not decreased in high-stage neuroblastoma, linking the L27-mediated LIN7A interaction to tumor-suppressive function. Co-IP/pulldown between DLG2 isoform 7 and LIN7A, isoform-specific expression in SKNAS cells, cell viability/proliferation assays, apoptosis marker analysis Cancer cell international Medium 33726762
2022 Rho-kinase/ROCK directly phosphorylates PSD-93 at Thr612 downstream of NMDAR activation; NMDAR agonist stimulation increases this phosphorylation in striatal slices; phosphorylation at Thr612 increases PSD-93 binding to PSD-95 and NMDARs; chemical-LTP induction (glycine) increases PSD-93 Thr612 phosphorylation, spine size, and PSD-93/PSD-95 co-localization, all blocked by Rho-kinase inhibitor. In vitro kinase assay, phospho-specific antibody, LC-MS/MS interactome analysis, Co-IP, chemical-LTP in neurons, Rho-kinase inhibitor pharmacology International journal of molecular sciences Medium 36613848
2022 Heterozygous Dlg2+/- rats show increased potassium channel function leading to decreased input resistance and impaired supra-linear dendritic integration, resulting in deficits in associative LTP; NMDA receptor-mediated currents are increased (not decreased); blockade of potassium channels or activation of muscarinic M1 receptors rescued the LTP impairment, placing DLG2 as a regulator of potassium channel activity that gates dendritic integration and synaptic plasticity. Heterozygous Dlg2+/- rat, patch-clamp electrophysiology, pharmacology (potassium channel blockers, M1 agonist 77-LH-28-1), computational modeling Neuropsychopharmacology High 35115661
2022 DLG2 KO in human embryonic stem cells impairs transcriptional programs of early cortical neurogenesis, resulting in deficits in neuronal migration, morphology, and action potential generation, establishing DLG2 as required for proper excitatory cortical neuronal differentiation and maturation. DLG2 KO hESC lines, cortical neuron differentiation, transcriptomics, neuronal migration assay, morphological analysis, electrophysiology (action potential recording) Nature communications High 35031607
2022 A DLG2 deficiency causes compensatory increases of DLG4/PSD-95 and decreases in TrkA expression in the striatum; the density of postsynaptic densities and fraction of perforated synapses are significantly reduced in Dlg2 KO dorsolateral striatum, with reduced dendritic spine density in striatal SPNs but not in cortical pyramidal neurons, demonstrating a striatum-specific requirement for DLG2 in synapse formation. Transmission electron microscopy, miniature EPSC recording, dendritic spine analysis, Western blot, Dlg2 KO mouse Frontiers in molecular neuroscience High 35966008
2022 DLG2 overexpression in colon cancer cells increases expression of IL1B, IκBζ, and BAX (components of inflammasome formation), while DLG2 silencing increases IL-6 secretion leading to STAT3 phosphorylation in bystander cells; restoration of DLG2 reduces AKT and S6 signaling, linking DLG2 to inflammasome regulation and suppression of AKT/S6 signaling. DLG2 overexpression and siRNA knockdown in colon cancer cells, cytokine ELISA, Western blot (phospho-STAT3, phospho-AKT, phospho-S6), conditioned medium transfer assay Journal of cancer research and clinical oncology Medium 35499706
2022 DLG2 overexpression in neuroblastoma cells reduces DNA fragmentation after UVC irradiation, induces apoptosis in a p53 S46-dependent manner, causes CHK1 phosphorylation, and impairs expression of NHEJ genes PARP1 and FEN1; in Drosophila with UVC-induced breaks, DLG2 overexpression similarly reduces DNA fragmentation, supporting a role for DLG2 in DNA damage response and genome integrity maintenance. Comet assay, γH2AX immunofluorescence, qRT-PCR and Western blot, Drosophila UVC model, phospho-p53 and phospho-CHK1 Western blot DNA repair Medium 35217496
2026 Src kinase phosphorylates PSD-93 at multiple tyrosine sites in vitro more robustly than PSD-95; phosphorylation differentially reduces PSD-93 affinity for postsynaptic client proteins and inhibits PSD-93 scaffolding activity (recruitment of clients into supercomplexes) while having opposite effects on PSD-95; phosphorylation of PSD-93 (but not PSD-95) affects biomolecular condensation, suggesting PSD-93 modulates condensate properties at higher protein concentrations. In vitro Src kinase assay, fluorescence polarization binding assay, small angle X-ray scattering, single-molecule FRET, supercomplex/scaffolding assay Protein science Medium 41562278
2020 The DLG2 F900V missense variant (associated with autosomal dominant delayed puberty) impairs the interaction between PSD-93 and Fyn kinase; this variant decreased GnRH expression in a GnRH neuronal cell line, suggesting that DLG2/PSD-93 regulates GnRH secretion through Fyn-dependent NMDA receptor signaling. Exome sequencing, Co-IP (interaction assay for F900V vs Fyn), GnRH expression assay in neuronal cell line Genetics in medicine Medium 32341572

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Neuron 492 8755482
2008 Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity. The Journal of physiology 133 18936077
2011 PSD-95 and PSD-93 play critical but distinct roles in synaptic scaling up and down. The Journal of neuroscience : the official journal of the Society for Neuroscience 111 21543610
2001 Electron microscopic immunocytochemical detection of PSD-95, PSD-93, SAP-102, and SAP-97 at postsynaptic, presynaptic, and nonsynaptic sites of adult and neonatal rat visual cortex. Synapse (New York, N.Y.) 109 11309840
2004 PSD93 regulates synaptic stability at neuronal cholinergic synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 93 14724236
2001 PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum. The Journal of neuroscience : the official journal of the Society for Neuroscience 89 11312293
2010 In vivo composition of NMDA receptor signaling complexes differs between membrane subdomains and is modulated by PSD-95 and PSD-93. The Journal of neuroscience : the official journal of the Society for Neuroscience 74 20554866
2018 Cross-species genomics identifies DLG2 as a tumor suppressor in osteosarcoma. Oncogene 65 30093633
2003 Effect of knock down of spinal cord PSD-93/chapsin-110 on persistent pain induced by complete Freund's adjuvant and peripheral nerve injury. Pain 54 14581127
2008 Distribution of the scaffolding proteins PSD-95, PSD-93, and SAP97 in isolated PSDs. Brain cell biology 49 18392731
2003 Identification of PSD-93 as a substrate for the Src family tyrosine kinase Fyn. The Journal of biological chemistry 45 13129934
2017 Hypersocial behavior and biological redundancy in mice with reduced expression of PSD95 or PSD93. Behavioural brain research 41 28189758
2020 Circ0106714 inhibits tumorigenesis of colorectal cancer by sponging miR-942-5p and releasing DLG2 via Hippo-YAP signaling. Molecular carcinogenesis 36 33128289
2020 11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma. Cell reports 35 32966799
1995 A gene (DLG2) located at 17q12-q21 encodes a new homologue of the Drosophila tumor suppressor dIg-A. Genomics 34 7590743
2019 MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2. Cancer biology & therapy 32 30862230
2020 A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum. Molecular autism 30 32164788
2017 PSD-93 Attenuates Amyloid-β-Mediated Cognitive Dysfunction by Promoting the Catabolism of Amyloid-β. Journal of Alzheimer's disease : JAD 30 28697571
2022 Region-based analysis of rare genomic variants in whole-genome sequencing datasets reveal two novel Alzheimer's disease-associated genes: DTNB and DLG2. Molecular psychiatry 29 35246634
2004 An alternatively spliced isoform of PSD-93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. The Journal of biological chemistry 29 15304517
2019 MicroRNA-152-3p protects neurons from oxygen-glucose-deprivation/reoxygenation-induced injury through upregulation of Nrf2/ARE antioxidant signaling by targeting PSD-93. Biochemical and biophysical research communications 27 31326116
2017 Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability. Genome medicine 27 28724449
2022 Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants. Nature communications 26 35031607
2020 PSD-93 Interacts with SynGAP and Promotes SynGAP Ubiquitination and Ischemic Brain Injury in Mice. Translational stroke research 26 32130656
2014 PSD-93 deletion inhibits Fyn-mediated phosphorylation of NR2B and protects against focal cerebral ischemia. Neurobiology of disease 26 24787897
2010 Tumor Suppressor RARRES1 Regulates DLG2, PP2A, VCP, EB1, and Ankrd26. Journal of Cancer 26 20842219
2003 Neonatal hypoxia-ischemia differentially upregulates MAGUKs and associated proteins in PSD-93-deficient mouse brain. Stroke 26 14605317
2023 Extracellular vesicles carrying miR-6836 derived from resistant tumor cells transfer cisplatin resistance of epithelial ovarian cancer via DLG2-YAP1 signaling pathway. International journal of biological sciences 24 37416779
2004 Targeted disruption of PSD-93 gene reduces platelet-activating factor-induced neurotoxicity in cultured cortical neurons. Experimental neurology 21 15296832
2017 DLG2, but not TMEM229B, GPNMB, and ITGA8 polymorphism, is associated with Parkinson's disease in a Taiwanese population. Neurobiology of aging 19 29290481
2022 Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 18 35115661
2022 Inflammation suppresses DLG2 expression decreasing inflammasome formation. Journal of cancer research and clinical oncology 18 35499706
2012 Interactions and phosphorylation of postsynaptic density 93 (PSD-93) by extracellular signal-regulated kinase (ERK). Brain research 16 22618309
2020 SNPs in SNCA, MCCC1, DLG2, GBF1 and MBNL2 are associated with Parkinson's disease in southern Chinese population. Journal of cellular and molecular medicine 15 32652860
2020 E2f8 and Dlg2 genes have independent effects on impaired insulin secretion associated with hyperglycaemia. Diabetologia 14 32356104
2006 Differential expression of a new isoform of DLG2 in renal oncocytoma. BMC cancer 14 16640776
2024 Glioma stem cell-derived exosomes induce the transformation of astrocytes via the miR-3065-5p/DLG2 signaling axis. Glia 12 38234042
2022 Selective behavioural impairments in mice heterozygous for the cross disorder psychiatric risk gene DLG2. Genes, brain, and behavior 12 35118804
2022 Rho-Kinase/ROCK Phosphorylates PSD-93 Downstream of NMDARs to Orchestrate Synaptic Plasticity. International journal of molecular sciences 12 36613848
2020 LncRNA DLG2-AS1 as a Novel Biomarker in Lung Adenocarcinoma. Cancers 12 32731343
2021 PSD-93 mediates the crosstalk between neuron and microglia and facilitates acute ischemic stroke injury by binding to CX3CL1. Journal of neurochemistry 11 33599284
2020 All-trans Retinoic Acid-induced Abnormal Hippocampal Expression of Synaptic Genes SynDIG1 and DLG2 is Correlated with Anxiety or Depression-Like Behavior in Mice. International journal of molecular sciences 11 32290523
2010 Effect of PSD-95/SAP90 and/or PSD-93/chapsyn-110 deficiency on the minimum alveolar anesthetic concentration of halothane in mice. Anesthesiology 11 20460989
2022 DLG2 impairs dsDNA break repair and maintains genome integrity in neuroblastoma. DNA repair 10 35217496
2015 Proteomic analysis of PSD-93 knockout mice following the induction of ischemic cerebral injury. Neurotoxicology 10 26680505
2013 Decrease in neuronal nicotinic acetylcholine receptor subunit and PSD-93 transcript levels in the male mouse MPG after cavernous nerve injury or explant culture. American journal of physiology. Renal physiology 9 24049141
2020 DLG2 variants in patients with pubertal disorders. Genetics in medicine : official journal of the American College of Medical Genetics 8 32341572
2018 Identification of a novel Dlg2 isoform differentially expressed in IFNβ-producing plasmacytoid dendritic cells. BMC genomics 8 29703139
2009 Evaluation of DLG2 as a positional candidate for disposition index in African-Americans from the IRAS Family Study. Diabetes research and clinical practice 8 19931931
2022 Enhancing DLG2 Implications in Neuropsychiatric Disorders: Analysis of a Cohort of Eight Patients with 11q14.1 Imbalances. Genes 7 35627244
2021 The loss of DLG2 isoform 7/8, but not isoform 2, is critical in advanced staged neuroblastoma. Cancer cell international 7 33726762
2015 The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury. Cell biochemistry and biophysics 7 27259312
2023 A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/- rat model of genetic risk for psychiatric disorder. Genes, brain, and behavior 6 37705179
2022 Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder. Genes, brain, and behavior 5 35075790
2022 A Deficiency of the Psychiatric Risk Gene DLG2/PSD-93 Causes Excitatory Synaptic Deficits in the Dorsolateral Striatum. Frontiers in molecular neuroscience 5 35966008
2013 Interaction partners of PSD-93 studied by X-ray crystallography and fluorescence polarization spectroscopy. Acta crystallographica. Section D, Biological crystallography 5 23519667
2022 Silencing of AKIP1 Suppresses the Proliferation, Migration, and Epithelial-Mesenchymal Transition Process of Glioma Cells by Upregulating DLG2. BioMed research international 4 35111846
2025 METTL3-dependent DLG2 inhibits the malignant progression of cervical cancer by inactivating the Hippo/YAP signaling. Hereditas 3 39856747
2021 DLG2 Mutations in the Etiology of Pubertal Delay and Idiopathic Hypogonadotropic Hypogonadism. Hormone research in paediatrics 2 34695822
2023 DLG2 intragenic exonic deletions reinforce the link to neurodevelopmental disorders and suggest a potential association with congenital anomalies and dysmorphism. Genetics in medicine : official journal of the American College of Medical Genetics 1 37860969
2023 Impaired reversal learning in the Dlg2+/- rat model of genetic risk for psychiatric disorder: Important questions regarding the neuro-behavioral mechanisms of reversal learning. Genes, brain, and behavior 1 38123893
2026 Differences in Src phosphorylation of PSD-93 and PSD-95 drive differences in scaffolding activity. Protein science : a publication of the Protein Society 0 41562278
2026 DLG2-DLG4 Expression Is Associated with Improved Survival and a Synaptic Gene Signature in Lower-Grade Glioma. Cancers 0 42193005
2025 DLG2 rs11607886 polymorphism associated with schizophrenia and precuneus functional changes. Schizophrenia research 0 40220608

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