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
Cellular Component: cortical cytoskeleton; dendrite cytoplasm; postsynaptic membrane; synaptic vesicle; extrinsic to internal side of plasma membrane; postsynaptic density; plasma membrane; ionotropic glutamate receptor complex; excitatory synapse; synapse; cell junction
Molecular Function: protein C-terminus binding; P2Y1 nucleotide receptor binding; ATP-activated nucleotide receptor activity; ionotropic glutamate receptor binding; protein binding; protein phosphatase binding; PDZ domain binding; ADP-activated nucleotide receptor activity
Biological Process: regulation of long-term neuronal synaptic plasticity; nervous system development; axon guidance; synaptic vesicle maturation; learning; social behavior; signal transduction; positive regulation of synaptic transmission; synaptic transmission; establishment of protein localization; protein complex assembly; positive regulation of transcription from RNA polymerase II promoter; neuromuscular process controlling balance; adenosine receptor signaling pathway
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
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.