DLGAP1

Discs, large (Drosophila) homolog-associated protein 1
Identifiers
Symbols	DLGAP1 ; DAP-1; DAP-1-ALPHA; DAP-1-BETA; DAP1; DLGAP1A; DLGAP1B; GKAP; SAPAP1
External IDs	OMIM: 605445 MGI: 1346065 HomoloGene: 31258 GeneCards: DLGAP1 Gene
Gene ontology Molecular function • protein binding Cellular component • cellular_component • cell junction • postsynaptic membrane • neuronal postsynaptic density Biological process • synaptic transmission Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9229	224997
Ensembl	ENSG00000170579	ENSMUSG00000003279
UniProt	O14490	Q9D415
RefSeq (mRNA)	NM_001003809	NM_001128180
RefSeq (protein)	NP_001003809	NP_001121652
Location (UCSC)	Chr 18: 3.5 – 4.46 Mb	Chr 17: 69.97 – 70.82 Mb
PubMed search

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

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.

References

1. "Entrez Gene: DLGAP1 discs, large (Drosophila) homolog-associated protein 1".
2. Hines RM, El-Husseini A (2006). "Mechanisms that regulate neuronal protein clustering at the synapse". In El-Husseini A, Dityatev A. Molecular mechanisms of synaptogenesis. Berlin: Springer. pp. 72–75. ISBN 0-387-32560-3.
3. Takeuchi M, Hata Y, Hirao K, Toyoda A, Irie M, Takai Y (May 1997). "SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density". J. Biol. Chem. 272 (18): 11943–51. doi:10.1074/jbc.272.18.11943. PMID 9115257.
4. Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, Matsumine A, Kobayashi S, Toyoshima K, Akiyama T (June 1997). "DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95". Genes Cells 2 (6): 415–24. doi:10.1046/j.1365-2443.1997.1310329.x. PMID 9286858.
5. Wu H, Reissner C, Kuhlendahl S, Coblentz B, Reuver S, Kindler S, Gundelfinger ED, Garner CC (November 2000). "Intramolecular interactions regulate SAP97 binding to GKAP". EMBO J. 19 (21): 5740–51. doi:10.1093/emboj/19.21.5740. PMC 305801. PMID 11060025.
6. Kim E, Naisbitt S, Hsueh YP, Rao A, Rothschild A, Craig AM, Sheng M (February 1997). "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. doi:10.1083/jcb.136.3.669. PMC 2134290. PMID 9024696.
7. Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, Weinberg RJ, Sheng M (June 2000). "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. PMID 10844022.
8. Boeckers TM, Winter C, Smalla KH, Kreutz MR, Bockmann J, Seidenbecher C, Garner CC, Gundelfinger ED (October 1999). "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. doi:10.1006/bbrc.1999.1489. PMID 10527873.
9. Hirao K, Hata Y, Ide N, Takeuchi M, Irie M, Yao I; et al. (1998). "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. doi:10.1074/jbc.273.33.21105. PMID 9694864.

Further reading

• Kim E, Naisbitt S, Hsueh YP; et al. (1997). "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. doi:10.1083/jcb.136.3.669. PMC 2134290. PMID 9024696.
• Takeuchi M, Hata Y, Hirao K; et al. (1997). "SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density.". J. Biol. Chem. 272 (18): 11943–51. doi:10.1074/jbc.272.18.11943. PMID 9115257.
• Naisbitt S, Kim E, Weinberg RJ; et al. (1997). "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. PMID 9221768.
• Satoh K, Yanai H, Senda T; et al. (1997). "DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95.". Genes Cells 2 (6): 415–24. doi:10.1046/j.1365-2443.1997.1310329.x. PMID 9286858.
• Hirao K, Hata Y, Ide N; et al. (1998). "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. doi:10.1074/jbc.273.33.21105. PMID 9694864.
• Deguchi M, Hata Y, Takeuchi M; et al. (1998). "BEGAIN (brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein.". J. Biol. Chem. 273 (41): 26269–72. doi:10.1074/jbc.273.41.26269. PMID 9756850.
• Kawabe H, Hata Y, Takeuchi M; et al. (1999). "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. doi:10.1074/jbc.274.43.30914. PMID 10521485.
• Boeckers TM, Winter C, Smalla KH; et al. (1999). "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. doi:10.1006/bbrc.1999.1489. PMID 10527873.
• Naisbitt S, Valtschanoff J, Allison DW; et al. (2000). "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. PMID 10844022.
• Wu H, Reissner C, Kuhlendahl S; et al. (2000). "Intramolecular interactions regulate SAP97 binding to GKAP.". EMBO J. 19 (21): 5740–51. doi:10.1093/emboj/19.21.5740. PMC 305801. PMID 11060025.
• Haraguchi K, Satoh K, Yanai H; et al. (2001). "The hDLG-associated protein DAP interacts with dynein light chain and neuronal nitric oxide synthase.". Genes Cells 5 (11): 905–911. doi:10.1046/j.1365-2443.2000.00374.x. PMID 11122378.
• Lo KW, Naisbitt S, Fan JS; et al. (2001). "The 8-kDa dynein light chain binds to its targets via a conserved (K/R)XTQT motif.". J. Biol. Chem. 276 (17): 14059–66. doi:10.1074/jbc.M010320200. PMID 11148209.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Im YJ, Lee JH, Park SH; et al. (2004). "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. doi:10.1074/jbc.M306919200. PMID 12954649.
• Ballif BA, Villén J, Beausoleil SA; et al. (2005). "Phosphoproteomic analysis of the developing mouse brain.". Mol. Cell Proteomics 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
• Suzuki T, Li W, Zhang JP; et al. (2005). "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. doi:10.1111/j.1460-9568.2005.03856.x. PMID 15673434.
• Sabio G, Arthur JS, Kuma Y; et al. (2005). "p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP.". EMBO J. 24 (6): 1134–45. doi:10.1038/sj.emboj.7600578. PMC 556394. PMID 15729360.