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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: basolateral plasma membrane; cell junction; cortical cytoskeleton; cytoplasm; cytosol; dendrite cytoplasm; dendritic spine; endoplasmic reticulum; excitatory synapse; extrinsic to internal side of plasma membrane; ionotropic glutamate receptor complex; plasma membrane; postsynaptic density; postsynaptic membrane; synapse; synaptic vesicle; voltage-gated potassium channel complex
Molecular Function: acetylcholine receptor binding; beta-1 adrenergic receptor binding; D1 dopamine receptor binding; guanylate kinase activity; ionotropic glutamate receptor binding; kinase binding; ligand-gated ion channel activity; P2Y1 nucleotide receptor binding; PDZ domain binding; protein binding; protein C-terminus binding; protein complex binding; protein phosphatase binding; Ras guanyl-nucleotide exchange factor activity
Biological Process: elevation of cytosolic calcium ion concentration; establishment and/or maintenance of epithelial cell polarity; establishment of protein localization; learning; MAPKKK cascade; negative regulation of receptor internalization; nervous system development; positive regulation of synaptic transmission; protein complex assembly; regulation of long-term neuronal synaptic plasticity; signal transduction; synaptic transmission; synaptic vesicle maturation
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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