DLGAP2 explained

Disks large-associated protein 2 is a protein that in humans is encoded by the DLGAP2 gene.^{[1] [2] [3]}

Function

The product of this gene is one of the membrane-associated guanylate kinases localized at postsynaptic density in neuronal cells. These kinases are a family of signaling molecules expressed at various submembrane domains and contain the PDZ, SH3 and the guanylate kinase domains. This protein may play a role in the molecular organization of synapses and in neuronal cell signaling. Alternatively spliced transcript variants encoding different isoforms have been identified, but their full-length nature is not known.

Interactions

DLGAP2 has been shown to interact with DLG4, the canonical synapse marker protein, which in turn binds to N-Methyl-d-aspartate (NMDA) receptors and Shaker-type K+ channels.^[4]

Clinical significance

As with many other synaptic genes, including its binding partner Shank2, DLGAP2 has been shown to be associated with Autism.^[5]

Further reading

• Takeuchi M, Hata Y, Hirao K . SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density . J. Biol. Chem. . 272 . 18 . 11943–51 . 1997 . 9115257 . 10.1074/jbc.272.18.11943 . etal. free .
• Naisbitt S, Kim E, Weinberg RJ . Characterization of guanylate kinase-associated protein, a postsynaptic density protein at excitatory synapses that interacts directly with postsynaptic density-95/synapse-associated protein 90 . J. Neurosci. . 17 . 15 . 5687–96 . 1997 . 9221768 . 10.1523/JNEUROSCI.17-15-05687.1997. 6573205 . etal. free .
• Ranta S, Lehesjoki AE, de Fatima Bonaldo M . High-resolution mapping and transcript identification at the progressive epilepsy with mental retardation locus on chromosome 8p . Genome Res. . 7 . 9 . 887–96 . 1997 . 9314494 . 10.1101/gr.7.9.887 . etal. free .
• Hirao K, Hata Y, Ide N . A novel multiple PDZ domain-containing molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins . J. Biol. Chem. . 273 . 33 . 21105–10 . 1998 . 9694864 . 10.1074/jbc.273.33.21105 . etal. free .
• Kawabe H, Hata Y, Takeuchi M . nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP) . J. Biol. Chem. . 274 . 43 . 30914–8 . 1999 . 10521485 . 10.1074/jbc.274.43.30914 . etal. free .
• Hirao K, Hata Y, Deguchi M . Association of synapse-associated protein 90/ postsynaptic density-95-associated protein (SAPAP) with neurofilaments . Genes Cells . 5 . 3 . 203–10 . 2000 . 10759891 . 10.1046/j.1365-2443.2000.00318.x . 2712385 . etal. free .
• Wang P, Zhang Q, Tochio H . Formation of a native-like beta-hairpin finger structure of a peptide from the extended PDZ domain of neuronal nitric oxide synthase in aqueous solution . Eur. J. Biochem. . 267 . 11 . 3116–22 . 2000 . 10824095 . 10.1046/j.1432-1327.2000.01318.x . etal. free .
• Bolliger MF, Frei K, Winterhalter KH, Gloor SM . Identification of a novel neuroligin in humans which binds to PSD-95 and has a widespread expression . Biochem. J. . 356 . Pt 2 . 581–8 . 2001 . 11368788 . 10.1042/0264-6021:3560581 . 1221872 .
• Hu LA, Chen W, Premont RT . G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95 . J. Biol. Chem. . 277 . 2 . 1607–13 . 2002 . 11700307 . 10.1074/jbc.M107297200 . etal. free .
• Ohtakara K, Nishizawa M, Izawa I . Densin-180, a synaptic protein, links to PSD-95 through its direct interaction with MAGUIN-1 . Genes Cells . 7 . 11 . 1149–60 . 2003 . 12390249 . 10.1046/j.1365-2443.2002.00589.x . 17177670 . etal. free .
• Verhoeven K, De Jonghe P, Van de Putte T . Slowed conduction and thin myelination of peripheral nerves associated with mutant rho Guanine-nucleotide exchange factor 10 . Am. J. Hum. Genet. . 73 . 4 . 926–32 . 2003 . 14508709 . 10.1086/378159 . 1180612 . etal.
• Ying Z, Bingaman W, Najm IM . Increased numbers of coassembled PSD-95 to NMDA-receptor subunits NR2B and NR1 in human epileptic cortical dysplasia . Epilepsia . 45 . 4 . 314–21 . 2004 . 15030493 . 10.1111/j.0013-9580.2004.37703.x . 46018257 .

Notes and References

1. Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, Matsumine A, Kobayashi S, Toyoshima K, Akiyama T . DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95 . Genes Cells . 2 . 6 . 415–24 . Oct 1997 . 9286858 . 10.1046/j.1365-2443.1997.1310329.x . 8934092 . free .
2. Ranta S, Zhang Y, Ross B, Takkunen E, Hirvasniemi A, de la Chapelle A, Gilliam TC, Lehesjoki AE . Positional cloning and characterisation of the human DLGAP2 gene and its exclusion in progressive epilepsy with mental retardation . Eur J Hum Genet . 8 . 5 . 381–4 . Sep 2000 . 10854099 . 10.1038/sj.ejhg.5200440 . free .
3. Web site: Entrez Gene: DLGAP2 discs, large (Drosophila) homolog-associated protein 2.
4. Takeuchi M, Hata Y, Hirao K, Toyoda A, Irie M, Takai Y . SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density . J. Biol. Chem. . 272 . 18 . 11943–51 . 1997 . 9115257 . 10.1074/jbc.272.18.11943 . free .
5. Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R. Functional impact of global rare copy number variation in autism spectrum disorders. . Nature . 2010 . 466 . 7304 . 368–72 . 20531469 . 10.1038/nature09146 . 3021798 . 2010Natur.466..368P . etal.