PSD-95 a membrane associated guanylate kinase (MAGUK) scaffolding protein located in neural postsynaptic densities. Associates with NMDA receptor NR2 subunits via glutamate serine (aspartate/glutamate) valine motifs in the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Its overexpression or depletion changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. 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. May reduce the amplitude of ACCN3 acid-evoked currents by retaining the channel intracellularly. Binds tissue-type plasminogen activator (tPA), mediating neural NMDA gating via a complex of LRP1, PSD-95 and NMDAR. Interacts through its first two PDZ domains with NMDAR2A, NMDAR2B, NMDAR2C, NMDAR2D, ACCN3, certain splice forms of NMDAR1, KV4.2, CXADR and synGAP. Interacts through its first two PDZ domains with Kv1.1, Kv1.2, Kv1.3, Kv1.4 and HER4. Interacts through its first PDZ domain with GluR6 and Kv1.4. Interacts through its second PDZ domain with the PDZ domain of nNOS or the C-terminus of NOS1AP. May interact with 5-HT(2A). Interacts through its third PDZ domain with NLGN1, and probably with NLGN2 and NLGN3. Interacts through its guanylate kinase-like domain with SAPAP1, SAPAP2, SAPAP3, SAPAP4, MAP1A, and BEGAIN. Interacts through its guanylate kinase-like domain with KIF13B. Two alternatively spliced human isoforms have been reported. Palmitoylation of isoform 1 is required for targeting to postsynaptic density. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold
Chromosomal Location of Human Ortholog: 17p13.1
Cellular Component:  AMPA glutamate receptor complex; cell junction; cerebellar mossy fiber; cortical cytoskeleton; cytoplasm; cytosol; dendrite cytoplasm; dendritic spine; endocytic vesicle membrane; endoplasmic reticulum; excitatory synapse; extrinsic component of cytoplasmic side of plasma membrane; glutamatergic synapse; juxtaparanode region of axon; neuron projection terminus; neuron spine; plasma membrane; postsynaptic density; postsynaptic membrane; synapse; synaptic membrane; synaptic vesicle
Molecular Function:  acetylcholine receptor binding; beta-1 adrenergic receptor binding; D1 dopamine receptor binding; ionotropic glutamate receptor binding; kinase binding; neuroligin family protein binding; P2Y1 nucleotide receptor binding; PDZ domain binding; protein binding; protein C-terminus binding; protein phosphatase binding; protein-containing complex binding; scaffold protein binding
Biological Process:  AMPA glutamate receptor clustering; cellular response to potassium ion; dendritic spine morphogenesis; establishment of protein localization; learning; locomotory exploration behavior; MAPK cascade; negative regulation of receptor internalization; nervous system development; neuromuscular process controlling balance; positive regulation of cytosolic calcium ion concentration; positive regulation of excitatory postsynaptic potential; positive regulation of neuron projection arborization; positive regulation of protein tyrosine kinase activity; positive regulation of synaptic transmission; protein localization to synapse; protein-containing complex assembly; receptor localization to synapse; regulation of grooming behavior; regulation of long-term neuronal synaptic plasticity; regulation of NMDA receptor activity; signal transduction; social behavior; synaptic vesicle maturation; vocalization behavior
Reference #:  P78352 (UniProtKB)
Alt. Names/Synonyms: discs large homolog 4; discs, large homolog 4 (Drosophila); Disks large homolog 4; DLG4; FLJ97752; FLJ98574; post-synaptic density protein 95; Postsynaptic density protein 95; PSD-95; PSD95; SAP-90; SAP90; Synapse-associated protein 90; Tax interaction protein 15
Gene Symbols: DLG4
Molecular weight: 80,495 Da
Basal Isoelectric point: 5.58  Predict pI for various phosphorylation states
CST Pathways:  ErbB/HER Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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