DLG4

PSD-95 (postsynaptic density protein 95) also known as SAP-90 (synapse-associated protein 90) is a protein that in humans is encoded by the DLG4 (discs large homolog 4) gene.^[5][6][7]

DLG4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KEF, 3I4W, 3K82, 3ZRT
Identifiers
Aliases	DLG4, PSD95, SAP-90, SAP90, Dlgh4, PSD-95, SAP90A, discs large homolog 4, discs large MAGUK scaffold protein 4, MRD62
External IDs	OMIM: 602887 MGI: 1277959 HomoloGene: 1047 GeneCards: DLG4
Gene location (Human) Chr. Chromosome 17 (human)^[1] Band 17p13.1 Start 7,187,187 bp^[1] End 7,219,841 bp^[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)^[2] Band 11|11 B3 Start 69,907,768 bp^[2] End 69,938,348 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nucleus accumbens cingulate gyrus prefrontal cortex anterior pituitary Brodmann area 9 amygdala caudate nucleus ganglionic eminence putamen hypothalamus Top expressed in superior frontal gyrus cerebellar cortex entorhinal cortex ventromedial nucleus primary motor cortex hippocampus proper olfactory tubercle lateral hypothalamus mammillary body supraoptic nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function beta-1 adrenergic receptor binding PDZ domain binding protein-containing complex binding scaffold protein binding guanylate kinase activity P2Y1 nucleotide receptor binding acetylcholine receptor binding kinase binding protein C-terminus binding protein binding ionotropic glutamate receptor binding D1 dopamine receptor binding protein phosphatase binding neuroligin family protein binding ligand-gated ion channel activity Cellular component cytoplasm juxtaparanode region of axon endocytic vesicle membrane synaptic membrane postsynaptic membrane cell projection membrane postsynaptic density synaptic vesicle extrinsic component of cytoplasmic side of plasma membrane voltage-gated potassium channel complex cortical cytoskeleton plasma membrane dendritic spine synapse excitatory synapse cerebellar mossy fiber axon cell junction dendrite basolateral plasma membrane endoplasmic reticulum neuron spine AMPA glutamate receptor complex dendrite cytoplasm ionotropic glutamate receptor complex neuron projection terminus cell periphery cytosol postsynaptic density membrane postsynapse neuromuscular junction neuron projection glutamatergic synapse Biological process receptor localization to synapse regulation of grooming behavior regulation of long-term neuronal synaptic plasticity neuromuscular process controlling balance negative regulation of receptor internalization establishment of protein localization positive regulation of cytosolic calcium ion concentration learning nervous system development MAPK cascade locomotory exploration behavior regulation of NMDA receptor activity AMPA glutamate receptor clustering dendritic spine morphogenesis vocalization behavior positive regulation of synaptic transmission establishment or maintenance of epithelial cell apical/basal polarity positive regulation of excitatory postsynaptic potential social behavior synaptic vesicle maturation protein localization to synapse signal transduction GMP metabolic process GDP metabolic process chemical synaptic transmission transmembrane transport cellular response to potassium ion receptor clustering positive regulation of protein tyrosine kinase activity protein-containing complex assembly cell-cell adhesion postsynaptic neurotransmitter receptor diffusion trapping positive regulation of neuron projection arborization neurotransmitter receptor localization to postsynaptic specialization membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1742 13385 Ensembl ENSG00000132535 ENSMUSG00000020886 UniProt P78352 O14909 Q62108 RefSeq (mRNA) NM_001128827 NM_001365 NM_001321074 NM_001321075 NM_001321076 NM_001321077 NM_001369566 NM_001109752 NM_007864 NM_001370671 NM_001370672 NM_001370674 NM_001370675 RefSeq (protein) NP_001122299 NP_001308003 NP_001308004 NP_001308005 NP_001308006 NP_001356 NP_001103222 NP_031890 Location (UCSC) Chr 17: 7.19 – 7.22 Mb Chr 11: 69.91 – 69.94 Mb PubMed search ^[3] ^[4]
Wikidata
View/Edit Human View/Edit Mouse

PSD-95 is a member of the membrane-associated guanylate kinase (MAGUK) family. With PSD-93 it is recruited into the same NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins.^[5] PSD-95 is the best studied member of the MAGUK-family of PDZ domain-containing proteins. Like all MAGUK-family proteins, its basic structure includes three PDZ domains, an SH3 domain, and a guanylate kinase-like domain (GK) connected by disordered linker regions. It is almost exclusively located in the post synaptic density of neurons,^[8] and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA receptors, and potassium channels.^[9] It plays an important role in synaptic plasticity and the stabilization of synaptic changes during long-term potentiation.^[10]

MAGUK superfamily and constituent domains

PSD-95 (encoded by DLG4) is a member of the MAGUK superfamily, and part of a subfamily which also includes PSD-93, SAP97 and SAP102. The MAGUKs are defined by their inclusion of PDZ, SH3 and GUK domains, although many of them also contain regions homologous of CaMKII, WW and L27 domains.^[11] The GUK domain that they have is structurally very similar to that of the guanylate kinases, however it is known to be catalytically inactive as the P-Loop which binds ATP is absent. It is thought that the MAGUKs have subfunctionalized the GUK domain for their own purposes, primarily based on its ability to form protein-protein interactions with cytoskeleton proteins, microtubule/actin based machinery and molecules involved in signal transduction.

The PDZ domain which are contained in the MAGUKs in varying numbers, is replicated three times over in PSD-95. PDZ domains are short peptide binding sequences commonly found at the C-terminus of interacting proteins. The three copies within the gene have different binding partners, due to amino acid substitutions within the PSD-95 protein and its ligands. The SH3 domain is again a protein-protein interaction domain. Its family generally bind to PXXP sites, but in MAGUKs it is known to bind to other sites as well. One of the most well known features is that it can form an intramolecular bond with the GUK domain, creating what is known as a GUK-SH3 'closed' state. The regulatory mechanisms and function are unknown but it is hypothesized that it may involve a hook region and a calmodulin binding region located elsewhere in the gene.

Interactions

PSD-95 has been shown to interact with:

• ADAM22^[12]
• Beta-1 adrenergic receptor^[13]
• CACNG2^[14][15]
• CASK^[16]
• DLG3^[17]
• DLGAP1^{[18][19][20][21][22][23]}
• DLGAP2^[19]
• DYNLL1^[18]
• DYNLL2^[18]
• ERBB4^[24][25]
• EXOC4^[26][27]
• FYN^[28][29]
• FZD7^[30]
• GRIK1^[31]
• GRIK2^[32][33]
• GRIK5^[32][33]
• GRIN2A^{[21][28][34][35]}
• GRIN2B^{[26][34][36][37][38][39]}
• GRIN2C^[36]
• HER2/neu^[24]
• HGS^[16]
• KCNA2^[40]
• KCNA4^{[37][38][40][41]}
• KCNA5^[40][42]
• KCNJ12^{[37][43][44][45]}
• Kir2.1^[45]
• LGI1^[12]
• LRP1^[46]
• LRP2^[46][47]
• NLGN1^[34]
• NOS1^[48][49]
• PTK2B^[50]
• SEMA4C^[51] and
• SHANK2.^[18][20]

See also

• Postsynaptic density

References

1. GRCh38: Ensembl release 89: ENSG00000132535 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020886 – Ensembl, May 2017
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4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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External links

• DLG4 protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)