disks large homolog 4; postsynaptic density protein 95; PSD-95; synapse-associated protein 90; SAP90 (DLG4, PSD95)
Jump to navigation
Jump to search
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]
More general terms
Additional terms
- 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
References
- ↑ Sheng M. Molecular organization of the postsynaptic specialization. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7058-61. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11416187
- ↑ UniProt http://www.uniprot.org/uniprot/P78352.html
- ↑ 3.0 3.1 Cook DJ et al. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 2012 Mar 8; 483:213. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22388811