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disks large homolog 4; postsynaptic density protein 95; PSD-95; synapse-associated protein 90; SAP90 (DLG4, PSD95)

Function: - interacts with the cytoplasmic tail of NMDA receptor subunits & shaker-type K+ channels - required for synaptic plasticity associated with NMDA receptor signaling - may also bind to kainate receptors - overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons - may reduce the amplitude of ACCN3 acid-evoked currents by retaining the channel intracellularly - may regulate the intracellular trafficking of ADR1B - palmitoylation of isoform 1 is required for targeting to postsynaptic density (putative) - interacts with ANKS1B & PRR7 (putative) - interacts through its 1st 2 PDZ domains with GRIN2A, GRIN2B, GRIN2C, GRIN2D, ACCN3, certain splice forms of GRIN1, KCND2, CXADR & SYNGAP1 - binding to the ES[D/E]V motif of GRIN2B plays a role in localization of the NMDA receptor to the post synaptic density & for coupling of the NMDA receptor to signal transduction pathways - interacts through its 2nd PDZ domain with the PDZ domain of NOS1 or the C-terminus of CAPON - may interact with HTR2A - interacts through its guanylate kinase-like domain with DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A & BEGAIN - interacts through its 3rd PDZ domain with CRIPT (putative) - interacts through its 1st 2 PDZ domains with KCNA1, KCNA2, KCNA3, KCNA4 & ERBB4 - interacts through its 1st PDZ domain with GRIK2, KCNA4 & CRIPT - interacts through its 3rd PDZ domain with NLGN1, & probably with NLGN2 & NLGN3 - interacts through its guanylate kinase-like domain with KIF13B - isoform 2 interacts through an L27 domain with HGS/HRS & the 1st L27 domain of CASK - interacts with LRFN1 Structure: - 3rd PDZ domain mediates interaction with ADR1B - L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to post-synaptic density - belongs to the MAGUK family - contains 1 guanylate kinase-like domain - contains 3 PDZ domains (DHR domains) - contains 1 SH3 domain Compartment: - cell membrane; peripheral membrane protein - cell junction, synapse, postsynaptic cell membrane, postsynaptic density. cell junction, synapse - 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 Alternative splicing: named isoforms=2 Expression: brain Pharmacology: - PSD-95 inhibitors may limit damage from ischemic stroke in monkeys [3]

Interactions

molecular events

Related

disks large-associated protein 2; DAP-2; SAP90/PSD-95-associated protein 2; SAPAP2; PSD-95/SAP90-binding protein 2 (DLGAP2, DAP2) PSD-95 inhibitor

General

magk superfamily protein phosphoprotein scaffold protein

Properties

SIZE: entity length = 724 aa MW = 80 kD COMPARTMENT: synaptic membrane CELL: neuron MOTIF: cysteine residue {C3} MODIFICATION: palmitate COMPARTMENT: membrane cysteine residue {C5} MODIFICATION: palmitate COMPARTMENT: membrane PDZ domain NAME: PDZ domain SITE: 65-151 MOTIF: Ser phosphorylation site {S142} PDZ domain NAME: PDZ domain SITE: 160-246 MOTIF: Tyr phosphorylation site {Y240} Ser phosphorylation site {S295} PDZ domain NAME: PDZ domain SITE: 313-393 Tyr phosphorylation site {Y397} Ser phosphorylation site {S415} Ser phosphorylation site {S418} src homology 3 [SH3] domain SITE: 428-498 MOTIF: Tyr phosphorylation site {Y432} domain {534-709} MOTIF: Tyr phosphorylation site {Y580} Tyr phosphorylation site {Y604} Tyr phosphorylation site {Y701} HOMOLOGY: guanylate kinase Tyr phosphorylation site {Y715}

Database Correlations

OMIM 602887 UniProt P78352 PFAM correlations Entrez Gene 1742

References

  1. Sheng M. Molecular organization of the postsynaptic specialization. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7058-61. Review. PMID: 11416187
  2. UniProt :accession P78352
  3. Cook DJ et al. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 2012 Mar 8; 483:213. PMID: 22388811