Protein: Disks large homolog 4 (Postsynaptic density protein 95) (PSD-95) (Synapse-associated protein 90) (SAP-90) (SAP90) (P31016)
Organism: Rattus norvegicus (Rat)
Function: 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 (By similarity). 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.Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (By similarity).
Subcellular location: Cell membrane {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:14642282, ECO:0000269|PubMed:9115257, ECO:0000305|PubMed:11997254}; Lipid-anchor {ECO:0000269|PubMed:10629226}; Cytoplasmic side {ECO:0000269|PubMed:10629226}. Postsynaptic density {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:11483650, ECO:0000269|PubMed:26679993, ECO:0000269|PubMed:27307232, ECO:0000269|PubMed:27756895, ECO:0000269|PubMed:9115257}. Synapse {ECO:0000269|PubMed:11483650, ECO:0000269|PubMed:11502259, ECO:0000269|PubMed:14642282, ECO:0000269|PubMed:19596852, ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20962234, ECO:0000269|PubMed:27307232, ECO:0000269|PubMed:8922396, ECO:0000269|PubMed:9115257}. Cytoplasm {ECO:0000269|PubMed:9115257}. Cell projection, axon {ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:8922396}. Cell projection, dendritic spine {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:20628354, ECO:0000269|PubMed:26679993, ECO:0000269|PubMed:30021165}. Cell projection, dendrite {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:11483650}. Presynapse {ECO:0000269|PubMed:8922396}. Note=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 (PubMed:19596852). {ECO:0000269|PubMed:19596852, ECO:0000269|PubMed:8922396}.
Interaction partners:
- Glutamate receptor ionotropic, NMDA 3A
- Glutamate receptor ionotropic, NMDA 2B
- Neuroligin-1
- Disks large-associated protein 1
- Glutamate receptor ionotropic, NMDA 1
- Glutamate receptor ionotropic, NMDA 2A
- Receptor tyrosine-protein kinase erbB-4
- Glutamate receptor ionotropic, kainate 2
- Disks large homolog 3
- Ras/Rap GTPase-activating protein SynGAP
Sequence:
MDCLCIVTTKKYRYQDEDTPPLEHSPAHLPNQANSPPVIVNTDTLEAPGYELQVNGTEGEMEYEEITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGGAAAQDGRLRVNDSILFVNEVDVREVTHSAAVEALKEAGSIVRLYVMRRKPPAEKVMEIKLIKGPKGLGFSIAGGVGNQHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVMHEDAVAALKNTYDVVYLKVAKPSNAYLSDSYAPPDITTSYSQHLDNEISHSSYLGTDYPTAMTPTSPRRYSPVAKDLLGEEDIPREPRRIVIHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDQILSVNGVDLRNASHEQAAIALKNAGQTVTIIAQYKPEEYSRFEAKIHDLREQLMNSSLGSGTASLRSNPKRGFYIRALFDYDKTKDCGFLSQALSFRFGDVLHVIDAGDEEWWQARRVHSDSETDDIGFIPSKRRVERREWSRLKAKDWGSSSGSQGREDSVLSYETVTQMEVHYARPIIILGPTKDRANDDLLSEFPDKFGSCVPHTTRPKREYEIDGRDYHFVSSREKMEKDIQAHKFIEAGQYNSHLYGTSVQSVREVAEQGKHCILDVSANAVRRLQAAHLHPIAIFIRPRSLENVLEINKRITEEQARKAFDRATKLEQEFTECFSAIVEGDSFEEIYHKVKRVIEDLSGPYIWVPARERL