DLG4

This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Discs Large MAGUK Scaffold Protein 4

Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression.

AMPA glutamate receptor clustering Source: BHF-UCL
Cell-cell adhesion Source: GO_Central
Cellular response to potassium ion Source: ARUK-UCL
Chemical synaptic transmission Source: GO_Central
Dendritic spine morphogenesis Source: BHF-UCL
Establishment of protein localization Source: BHF-UCL
Learning Source: ProtInc
Locomotory exploration behavior Source: Ensembl
Negative regulation of receptor internalization Source: BHF-UCL
Nervous system development Source: ProtInc
Neuromuscular process controlling balance Source: Ensembl
Neurotransmitter receptor localization to postsynaptic specialization membrane Source: Ensembl
Positive regulation of cytosolic calcium ion concentration Source: BHF-UCL
Positive regulation of excitatory postsynaptic potential Source: BHF-UCL
Positive regulation of neuron projection arborization Source: ARUK-UCL
Positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
Positive regulation of synaptic transmission Source: BHF-UCL
Postsynaptic neurotransmitter receptor diffusion trapping Source: GO_Central
Protein-containing complex assembly Source: BHF-UCL
Protein localization to synapse Source: BHF-UCL
Receptor clustering Source: GO_Central
Receptor localization to synapse Source: BHF-UCL
Regulation of grooming behavior Source: Ensembl
Regulation of long-term neuronal synaptic plasticity Source: BHF-UCL
Regulation of NMDA receptor activity Source: BHF-UCL
Signal transduction Source: ProtInc
Social behavior Source: Ensembl
Synaptic vesicle maturation Source: BHF-UCL
Vocalization behavior Source: Ensembl

Cytoplasm; Cell membrane; Postsynaptic density; Synapse; Axon; Dendritic spine; Dendrite; Presynapse. High levels in postsynaptic density of neurons in the forebrain. Also in presynaptic region of inhibitory synapses formed by cerebellar basket cells on axon hillocks of Purkinje cells. Suppression of neuronal activity induces synaptic accumulation and clustering of DLG4.

Intellectual developmental disorder, autosomal dominant 62 (MRD62):
An autosomal dominant form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development.

Palmitoylated (PubMed:26701913). Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses (By similarity). Palmitoylation by ZDHHC2 occurs when the synaptic activity decreases and induces DLG4 synaptic clustering (By similarity). Palmitoylation by ZDHHC15 regulates trafficking to the postsynaptic density and function in synaptogenesis (By similarity). Palmitoylation may play a role in glutamate receptor GRIA1 synapse clustering (By similarity). Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2 (PubMed:26701913). Undergoes rapid synaptic palmitoylation/depalmitoylation cycles during neuronal development which slow down in mature neurons (By similarity).
Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.