DLG3

Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the DLG3 gene.[5][6] DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins.

DLG3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UM7, 2FE5, 2I1N
Identifiers
Aliases	DLG3, MRX, MRX90, NEDLG, PPP1R82, SAP102, XLMR, discs large homolog 3, discs large MAGUK scaffold protein 3
External IDs	OMIM: 300189 MGI: 1888986 HomoloGene: 41157 GeneCards: DLG3
Gene location (Human) Chr. X chromosome (human)[1] Band Xq13.1 Start 70,444,835 bp[1] End 70,505,490 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X C3 Start 100,767,722 bp[2] End 100,818,410 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphatase binding • PDZ domain binding • protein domain specific binding • guanylate kinase activity • kinase binding • protein C-terminus binding • GO:0001948 protein binding • ionotropic glutamate receptor binding • protein phosphatase binding • ubiquitin protein ligase binding • ligand-gated ion channel activity • Ras guanyl-nucleotide exchange factor activity • structural constituent of postsynaptic density Cellular component • cytoplasm • postsynaptic membrane • GO:0097483, GO:0097481 postsynaptic density • intercellular junction • bicellular tight junction • growth cone • cell membrane • synapse • dendritic shaft • neuronal cell body • basolateral plasma membrane • AMPA glutamate receptor complex • ionotropic glutamate receptor complex • extracellular • cytosol • cell junction • neuromuscular junction • neuron projection • postsynaptic density membrane • glutamatergic synapse • postsynaptic density, intracellular component Biological process • receptor localization to synapse • negative regulation of phosphatase activity • establishment of planar polarity • receptor clustering • nervous system development • establishment or maintenance of epithelial cell apical/basal polarity • negative regulation of cell proliferation • ion transmembrane transport • GMP metabolic process • GDP metabolic process • chemical synaptic transmission • MAPK cascade • positive regulation of protein tyrosine kinase activity • cell-cell adhesion • regulation of postsynaptic membrane neurotransmitter receptor levels • maintenance of postsynaptic density structure • regulation of NMDA receptor activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1741	53310
Ensembl	ENSG00000082458	ENSMUSG00000000881
UniProt	Q92796	P70175
RefSeq (mRNA)	NM_001166278 NM_020730 NM_021120	NM_001177778 NM_001177779 NM_001177780 NM_001290402 NM_016747
RefSeq (protein)	NP_001159750 NP_065781 NP_066943	NP_001171249 NP_001171250 NP_001171251 NP_001277331 NP_058027
Location (UCSC)	Chr X: 70.44 – 70.51 Mb	Chr X: 100.77 – 100.82 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

DLG3 has been shown to interact with:

• APC,[7]
• CRIPT,[8]
• DLG4,[9]
• EXOC3,[10]
• EXOC4,[10]
• GRIN2A,[8][11]
• GRIN2B,[8][10][11][12]
• GRIN2C,[8]
• KCNJ12[13]
• PTK2B,[14] and
• SYNGAP1.[15]

Model organisms

Model organisms have been used in the study of DLG3 function. A conditional knockout mouse line called Dlg3^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[16] Male and female animals underwent a standardized phenotypic screen[17] to determine the effects of deletion.[18][19][20][21] Additional screens performed: - In-depth immunological phenotyping[22]

Dlg3 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[17][22]
Peripheral blood leukocytes 6 Weeks	Normal
Insulin	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
General Observations	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

.

References

1. GRCh38: Ensembl release 89: ENSG00000082458 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000000881 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Stathakis DG, Lee D, Bryant PJ (Aug 1998). "DLG3, the gene encoding human neuroendocrine Dlg (NE-Dlg), is located within the 1.8-Mb dystonia-parkinsonism region at Xq13.1". Genomics. 49 (2): 310–3. doi:10.1006/geno.1998.5243. PMID 9598320.
6. "Entrez Gene: DLG3 Discs, large homolog 3 (neuroendocrine-dlg, Drosophila)".
7. Makino K, Kuwahara H, Masuko N, Nishiyama Y, Morisaki T, Sasaki J, Nakao M, Kuwano A, Nakata M, Ushio Y, Saya H (May 1997). "Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein". Oncogene. 14 (20): 2425–33. doi:10.1038/sj.onc.1201087. PMID 9188857.
8. Lim IA, Hall DD, Hell JW (Jun 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.
9. Masuko N, Makino K, Kuwahara H, Fukunaga K, Sudo T, Araki N, Yamamoto H, Yamada Y, Miyamoto E, Saya H (Feb 1999). "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90. A possible regulatory role in molecular clustering at synaptic sites". J. Biol. Chem. 274 (9): 5782–90. doi:10.1074/jbc.274.9.5782. PMID 10026200.
10. Sans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ (Jun 2003). "NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex". Nat. Cell Biol. 5 (6): 520–30. doi:10.1038/ncb990. PMID 12738960.
11. Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Südhof TC (Sep 1997). "Binding of neuroligins to PSD-95". Science. 277 (5331): 1511–5. doi:10.1126/science.277.5331.1511. PMID 9278515.
12. Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (Jun 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". Am. J. Physiol., Cell Physiol. 282 (6): C1396-403. doi:10.1152/ajpcell.00615.2001. PMID 11997254.
13. Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LM, Adams ME, Froehner SC, Yates JR, Vandenberg CA (May 2004). "Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins". J. Biol. Chem. 279 (21): 22331–46. doi:10.1074/jbc.M400285200. PMID 15024025.
14. Seabold GK, Burette A, Lim IA, Weinberg RJ, Hell JW (Apr 2003). "Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102". J. Biol. Chem. 278 (17): 15040–8. doi:10.1074/jbc.M212825200. PMID 12576483.
15. Kim JH, Liao D, Lau LF, Huganir RL (Apr 1998). "SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family". Neuron. 20 (4): 683–91. doi:10.1016/S0896-6273(00)81008-9. PMID 9581761.
16. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
17. "International Mouse Phenotyping Consortium".
18. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
19. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
20. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
21. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
22. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Lau LF, Mammen A, Ehlers MD, et al. (1996). "Interaction of the N-methyl-D-aspartate receptor complex with a novel synapse-associated protein, SAP102". J. Biol. Chem. 271 (35): 21622–8. doi:10.1074/jbc.271.35.21622. PMID 8702950.
• Müller BM, Kistner U, Kindler S, et al. (1996). "SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo". Neuron. 17 (2): 255–65. doi:10.1016/S0896-6273(00)80157-9. PMID 8780649.
• 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.
• Makino K, Kuwahara H, Masuko N, et al. (1997). "Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein". Oncogene. 14 (20): 2425–33. doi:10.1038/sj.onc.1201087. PMID 9188857.
• Irie M, Hata Y, Takeuchi M, et al. (1997). "Binding of neuroligins to PSD-95". Science. 277 (5331): 1511–5. doi:10.1126/science.277.5331.1511. PMID 9278515.
• Kim JH, Liao D, Lau LF, Huganir RL (1998). "SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family". Neuron. 20 (4): 683–91. doi:10.1016/S0896-6273(00)81008-9. PMID 9581761.
• Butz S, Okamoto M, Südhof TC (1998). "A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain". Cell. 94 (6): 773–82. doi:10.1016/S0092-8674(00)81736-5. PMID 9753324.
• Garcia EP, Mehta S, Blair LA, et al. (1998). "SAP90 binds and clusters kainate receptors causing incomplete desensitization". Neuron. 21 (4): 727–39. doi:10.1016/S0896-6273(00)80590-5. PMID 9808460.
• Masuko N, Makino K, Kuwahara H, et al. (1999). "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90. A possible regulatory role in molecular clustering at synaptic sites". J. Biol. Chem. 274 (9): 5782–90. doi:10.1074/jbc.274.9.5782. PMID 10026200.
• Kuwahara H, Araki N, Makino K, et al. (1999). "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and N-methyl-D-aspartate receptor". J. Biol. Chem. 274 (45): 32204–14. doi:10.1074/jbc.274.45.32204. PMID 10542258.
• Nagase T, Ishikawa K, Kikuno R, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (5): 337–45. doi:10.1093/dnares/6.5.337. PMID 10574462.
• Firestein BL, Firestein BL, Brenman JE, et al. (2000). "Cypin: a cytosolic regulator of PSD-95 postsynaptic targeting". Neuron. 24 (3): 659–72. doi:10.1016/S0896-6273(00)81120-4. PMID 10595517.
• Garcia RA, Vasudevan K, Buonanno A (2000). "The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3596–601. doi:10.1073/pnas.070042497. PMC 16285. PMID 10725395.
• Husi H, Ward MA, Choudhary JS, et al. (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nat. Neurosci. 3 (7): 661–9. doi:10.1038/76615. hdl:1842/742. PMID 10862698.
• Inagaki S, Ohoka Y, Sugimoto H, et al. (2001). "Sema4c, a transmembrane semaphorin, interacts with a post-synaptic density protein, PSD-95". J. Biol. Chem. 276 (12): 9174–81. doi:10.1074/jbc.M009051200. PMID 11134026.
• DeMarco SJ, Strehler EE (2001). "Plasma membrane Ca2+-atpase isoforms 2b and 4b interact promiscuously and selectively with members of the membrane-associated guanylate kinase family of PDZ (PSD95/Dlg/ZO-1) domain-containing proteins". J. Biol. Chem. 276 (24): 21594–600. doi:10.1074/jbc.M101448200. PMID 11274188.
• Russwurm M, Wittau N, Koesling D (2002). "Guanylyl cyclase/PSD-95 interaction: targeting of the nitric oxide-sensitive alpha2beta1 guanylyl cyclase to synaptic membranes". J. Biol. Chem. 276 (48): 44647–52. doi:10.1074/jbc.M105587200. PMID 11572861.
• Lim IA, Hall DD, Hell JW (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.
• Cai C, Coleman SK, Niemi K, Keinänen K (2002). "Selective binding of synapse-associated protein 97 to GluR-A alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionate receptor subunit is determined by a novel sequence motif". J. Biol. Chem. 277 (35): 31484–90. doi:10.1074/jbc.M204354200. PMID 12070168.