DLG4

Discs, large homolog 4 (Drosophila)
PDB rendering based on 1be9.
Available structures PDB 1KEF, 3I4W, 3K82
Identifiers
Symbols	DLG4; FLJ97752; FLJ98574; PSD95; SAP-90; SAP90
External IDs	OMIM: 602887 MGI: 1277959 HomoloGene: 1047 GeneCards: DLG4 Gene
Gene Ontology Molecular function • protein binding • protein C-terminus binding Cellular component • plasma membrane • plasma membrane • postsynaptic density • synaptosome • cell junction • endocytic vesicle membrane • cortical cytoskeleton • neuron spine • synapse • postsynaptic membrane Biological process • protein complex assembly • signal transduction • synaptic transmission • nervous system development • axon guidance • learning Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1742	13385
Ensembl	ENSG00000132535	ENSMUSG00000020886
UniProt	P78352	Q6XVF4
RefSeq (mRNA)	NM_001128827.1	NM_007864
RefSeq (protein)	NP_001122299.1	NP_031890
Location (UCSC)	Chr 17: 7.09 – 7.12 Mb	Chr 11: 69.83 – 69.86 Mb
PubMed search	[1]	[2]

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 (disks large homolog 4) gene.^[1][2][3]

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.^[1]

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,^[4] and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA receptors, and potassium channels.^[5]

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.^[6] 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 a 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^[7]
• Beta-1 adrenergic receptor^[8]
• CACNG2^[9][10]
• CASK^[11]
• DLG3^[12]
• DLGAP1^{[13][14][15][16][17][18]}
• DLGAP2^[14]
• DYNLL1^[13]
• DYNLL2^[13]
• ERBB4^[19][20]
• EXOC4^[21][22]
• FYN^[23][24]
• FZD7^[25]
• GRIK1^[26]
• GRIK2^[27][28]
• GRIK5^[27][28]
• GRIN2A^{[16][23][29][30]}
• GRIN2B^{[21][31][29][32][33][34]}
• GRIN2C^[31]
• HER2/neu^[19]
• HGS^[11]
• KCNA2^[35]
• KCNA4^{[32][33][35][36]}
• KCNA5^[35][37]
• KCNJ12^{[38][39][32][38][40]}
• Kir2.1^[40]
• LGI1^[7]
• LRP1^[41]
• LRP2^[41][42]
• NLGN1^[29]
• NOS1^[43][44]
• PTK2B^[45]
• SEMA4C^[46] and
• SHANK2.^[13][15]

See also

• Postsynaptic density

References

1. ^ ^{a b} "Entrez Gene: DLG4 discs, large homolog 4 (Drosophila)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1742. 
2. ^ Cho KO, Hunt CA, Kennedy MB (Nov 1992). "The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein.". Neuron 9 (5): 929–942. doi:10.1016/0896-6273(92)90245-9. PMID 1419001. 
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4. ^ Hunt CA, Schenker LJ, Kennedy MB (Feb 1996). "PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses.". Journal of Neuroscience 16 (4): 1380–1388. PMID 8778289. 
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31. ^ ^{a b} Lim IA, Hall DD, Hell JW (June 2002). "Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102". J. Biol. Chem. 277 (24): 21697–711. doi:10.1074/jbc.M112339200. PMID 11937501. 
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External links

• MeSH DLG4 protein, human