DLGAP1 explained

Disks large-associated protein 1 (DAP-1), also known as guanylate kinase-associated protein (GKAP), is a protein that in humans is encoded by the DLGAP1 gene. DAP-1 is known to be highly enriched in synaptosomal preparations of the brain, and present in the post-synaptic density.^[1]

Function

This gene encodes the protein called guanylate kinase-associated protein (GKAP). GKAP binds to the SHANK2 and PSD-95 proteins, facilitating the assembly of the post-synaptic density of neurons.^[2] Dlgap1 has five 14-amino-acid repeats and three Pro-rich portions.

Interactions

DLGAP1 has been shown to interact with:

• • DLG1 DLG4^{[3] [4] [5] [6] [7] [8]}
• DYNLL1^[7]
• DYNLL2^[7]
• SHANK2^{[7] [8]}

The interaction with PSD95 and S-SCAM is mediated by the GUK domain^[9] and it has been hypothesized that this might mean it can also interact with other GUK containing proteins.

Further reading

• Kim E, Naisbitt S, Hsueh YP . GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. . J. Cell Biol. . 136 . 3 . 669–78 . 1997 . 9024696 . 10.1083/jcb.136.3.669 . 2134290 . etal.
• 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 .
• Satoh K, Yanai H, Senda 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 . 1997 . 9286858 . 10.1046/j.1365-2443.1997.1310329.x . 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 .
• Deguchi M, Hata Y, Takeuchi M . BEGAIN (brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein. . J. Biol. Chem. . 273 . 41 . 26269–72 . 1998 . 9756850 . 10.1074/jbc.273.41.26269 . 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 .
• Boeckers TM, Winter C, Smalla KH . Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family. . Biochem. Biophys. Res. Commun. . 264 . 1 . 247–52 . 1999 . 10527873 . 10.1006/bbrc.1999.1489 . etal.
• Naisbitt S, Valtschanoff J, Allison DW . Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein. . J. Neurosci. . 20 . 12 . 4524–34 . 2000 . 10844022 . 10.1523/JNEUROSCI.20-12-04524.2000. etal. free . 6772433 .
• Wu H, Reissner C, Kuhlendahl S . Intramolecular interactions regulate SAP97 binding to GKAP. . EMBO J. . 19 . 21 . 5740–51 . 2000 . 11060025 . 10.1093/emboj/19.21.5740 . 305801 . etal.
• Haraguchi K, Satoh K, Yanai H . The hDLG-associated protein DAP interacts with dynein light chain and neuronal nitric oxide synthase. . Genes Cells . 5 . 11 . 905–911 . 2001 . 11122378 . 10.1046/j.1365-2443.2000.00374.x . etal. free .
• Lo KW, Naisbitt S, Fan JS . The 8-kDa dynein light chain binds to its targets via a conserved (K/R)XTQT motif. . J. Biol. Chem. . 276 . 17 . 14059–66 . 2001 . 11148209 . 10.1074/jbc.M010320200 . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Im YJ, Lee JH, Park SH . Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization. . J. Biol. Chem. . 278 . 48 . 48099–104 . 2004 . 12954649 . 10.1074/jbc.M306919200 . etal. free .
• Ballif BA, Villén J, Beausoleil SA . Phosphoproteomic analysis of the developing mouse brain. . Mol. Cell. Proteomics . 3 . 11 . 1093–101 . 2005 . 15345747 . 10.1074/mcp.M400085-MCP200 . etal. free .
• Suzuki T, Li W, Zhang JP . A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multiprotein complex with various postsynaptic density proteins. . Eur. J. Neurosci. . 21 . 2 . 339–50 . 2005 . 15673434 . 10.1111/j.1460-9568.2005.03856.x . 28773407 . etal.
• Sabio G . Guadalupe Sabio . Arthur JS . Kuma Y . p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP. . EMBO J. . 24 . 6 . 1134–45 . 2005 . 15729360 . 10.1038/sj.emboj.7600578 . 556394 . etal.

Notes and References

1. Web site: Entrez Gene: DLGAP1 discs, large (Drosophila) homolog-associated protein 1.
2. Book: El-Husseini A, Dityatev A . Molecular mechanisms of synaptogenesis . Springer . Berlin . 2006 . Mechanisms that regulate neuronal protein clustering at the synapse. Hines RM, El-Husseini A . 978-0-387-32560-6 . 72–75 .
3. May 1997 . 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 . 9115257 . 10.1074/jbc.272.18.11943. free .
4. June 1997 . 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 . 9286858 . 10.1046/j.1365-2443.1997.1310329.x. free .
5. November 2000 . Wu H, Reissner C, Kuhlendahl S, Coblentz B, Reuver S, Kindler S, Gundelfinger ED, Garner CC . Intramolecular interactions regulate SAP97 binding to GKAP . EMBO J. . 19 . 21 . 5740–51 . 11060025 . 305801 . 10.1093/emboj/19.21.5740.
6. February 1997 . Kim E, Naisbitt S, Hsueh YP, Rao A, Rothschild A, Craig AM, Sheng M . GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules . J. Cell Biol. . 136 . 3 . 669–78 . 9024696 . 2134290 . 10.1083/jcb.136.3.669.
7. June 2000 . Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, Weinberg RJ, Sheng M . Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein . J. Neurosci. . 20 . 12 . 4524–34 . 10844022 . 10.1523/JNEUROSCI.20-12-04524.2000. free . 6772433 .
8. October 1999 . Boeckers TM, Winter C, Smalla KH, Kreutz MR, Bockmann J, Seidenbecher C, Garner CC, Gundelfinger ED . Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family . Biochem. Biophys. Res. Commun. . 264 . 1 . 247–52 . 10527873 . 10.1006/bbrc.1999.1489.
9. Hirao K, Hata Y, Ide N, Takeuchi M, Irie M, Yao I. A novel multiple PDZ domain-containing molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins. . J Biol Chem . 1998 . 273 . 33 . 21105–10 . 9694864 . 10.1074/jbc.273.33.21105. etal. free .