DLG1

DLG1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PDR, 2M3M, 2OQS, 2X7Z, 3RL7, 3RL8, 3W9Y, 4AMH, 4G69
Identifiers
Aliases	DLG1, DLGH1, SAP-97, SAP97, dJ1061C18.1.1, hdlg, B130052P05Rik, E-dlg/SAP97, mKIAA4187, discs large homolog 1, scribble cell polarity complex component, discs large MAGUK scaffold protein 1
External IDs	MGI: 107231 HomoloGene: 20869 GeneCards: DLG1
Gene ontology Molecular function • phosphatase binding • phosphoprotein phosphatase activity • ion channel binding • cytoskeletal protein binding • protein C-terminus binding • ionotropic glutamate receptor binding • kinase binding • mitogen-activated protein kinase kinase binding • guanylate kinase activity • potassium channel regulator activity • protein binding • protein complex scaffold • protein kinase binding • L27 domain binding • ligand-gated ion channel activity • cadherin binding involved in cell-cell adhesion Cellular component • cytoplasm • cytosol • postsynaptic membrane • membrane • cell-cell junction • bicellular tight junction • node of Ranvier • synapse • perinuclear region of cytoplasm • cytoplasmic side of plasma membrane • microtubule • nucleus • cell projection membrane • membrane raft • ionotropic glutamate receptor complex • extracellular exosome • Golgi apparatus • lateral plasma membrane • intercalated disc • neuromuscular junction • myelin sheath abaxonal region • lateral loop • endoplasmic reticulum membrane • basal lamina • MPP7-DLG1-LIN7 complex • sarcolemma • postsynaptic density • cell junction • cell-cell adherens junction • basolateral plasma membrane • plasma membrane • endoplasmic reticulum • immunological synapse Biological process • embryonic skeletal system morphogenesis • ureteric bud development • positive regulation of actin filament polymerization • positive regulation of potassium ion transport • negative regulation of p38MAPK cascade • amyloid precursor protein metabolic process • tissue morphogenesis • reproductive structure development • membrane raft organization • hard palate development • endothelial cell proliferation • smooth muscle tissue development • negative regulation of epithelial cell proliferation • regulation of sodium ion transmembrane transport • astral microtubule organization • actin filament organization • mitotic cell cycle checkpoint • receptor clustering • positive regulation of establishment of protein localization to plasma membrane • establishment or maintenance of cell polarity • negative regulation of T cell proliferation • branching involved in ureteric bud morphogenesis • regulation of myelination • cortical microtubule organization • establishment or maintenance of epithelial cell apical/basal polarity • viral process • T cell cytokine production • T cell activation • chemical synaptic transmission • peristalsis • receptor localization to synapse • single organismal cell-cell adhesion • negative regulation of protein kinase B signaling • regulation of NIK/NF-kappaB signaling • negative regulation of transcription from RNA polymerase II promoter • nervous system development • regulation of cell shape • establishment of centrosome localization • immunological synapse formation • cortical actin cytoskeleton organization • protein localization • lens development in camera-type eye • cellular protein complex localization • bicellular tight junction assembly • positive regulation of cell proliferation • negative regulation of ERK1 and ERK2 cascade • activation of protein kinase activity • negative regulation of mitotic cell cycle • regulation of membrane potential • protein localization to plasma membrane • GDP metabolic process • ion transmembrane transport • protein dephosphorylation • GMP metabolic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1739	13383
Ensembl	ENSG00000075711	ENSMUSG00000022770
UniProt	Q12959	Q811D0
RefSeq (mRNA)	NM_001098424 NM_001204386 NM_001204387 NM_001204388 NM_001290983 NM_004087	NM_001252433 NM_001252434 NM_001252435 NM_001252436 NM_007862
RefSeq (protein)	NP_001091894.1 NP_001191315.1 NP_001191316.1 NP_001191317.1 NP_001277912.1 NP_004078.2	NP_001239362.1 NP_001239363.1 NP_001239364.1 NP_031888.2
Location (UCSC)	Chr 3: 197.04 – 197.3 Mb	Chr 16: 31.66 – 31.87 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

Disks large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a protein that in humans is encoded by the SAP97 gene.

SAP97 is a mammalian MAGUK-family member protein that is similar to the Drosophila protein Dlg1 (the protein is alternatively referred to as hDlg1, and the human gene is DLG1). SAP97 is expressed throughout the body in epithelial cells. In the brain it is involved in the trafficking of ionotropic receptors from the endoplasmic Reticulum to the plasma membrane, and may be involved in the trafficking AMPAR during synaptic plasticity.

Function

SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain.^[3] There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane.^[4]

SAP97's function has been investigated by reducing its expression by knockout or increasing its expression heterologously. Mice in which the SAP97 gene has been knocked out die perinatally, have a cleft palate, and deficiencies in renal function.^[5][6] Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength.^[7]

Clinical significance

Mutations in DLG1 are associated to Crohn's Disease .^[8]

Structure

SAP97's protein structure consists of an alternatively-spliced n-terminal domain, three PDZ domains, an SH3 domain, hook domain, I3 domain, and finally an inactive guanylate kinase (GK) domain. Each of these domains has specific interacting partners that help define SAP97's unique function.

The n-terminal of SAP97 can be alternatively spliced to contain a double-cysteine/palmitoylation site (α-isoform), or an L27 domain (β-isoform. The L27 domain is involved in SAP97 oligomerization with other SAP97 molecules, CASK, and other L27-domain-containing proteins.^[9] There is also a myosin VI binding site near n-terminal which may be involved in the internalization of AMPAR.^[10][11]

Each of SAP97's PDZ domains have different binding partners, including the AMPAR subunit GluR1^[12][13] for the first PDZ domain, and neuroligin for the last. SAP97's I3 domain is unique to SAP97 among the MAGUK family, and is known to regulate the post-synaptic localization of SAP97^[7] and to bind the protein 4.1N. The GK domain allows SAP97 to bind to GKAP/SAPAP-family proteins.

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Müller BM, Kistner U, Veh RW, Cases-Langhoff C, Becker B, Gundelfinger ED, Garner CC (Mar 1995). "Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein". The Journal of Neuroscience. 15 (3 Pt 2): 2354–66. PMID 7891172.
4. Sans N, Racca C, Petralia RS, Wang YX, McCallum J, Wenthold RJ (Oct 2001). "Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway". The Journal of Neuroscience. 21 (19): 7506–16. PMID 11567040.
5. Caruana G, Bernstein A (Mar 2001). "Craniofacial dysmorphogenesis including cleft palate in mice with an insertional mutation in the discs large gene". Molecular and Cellular Biology. 21 (5): 1475–83. doi:10.1128/MCB.21.5.1475-1483.2001. PMC 86693. PMID 11238884.
6. Mahoney ZX, Sammut B, Xavier RJ, Cunningham J, Go G, Brim KL, Stappenbeck TS, Miner JH, Swat W (Dec 2006). "Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter". Proceedings of the National Academy of Sciences of the United States of America. 103 (52): 19872–7. doi:10.1073/pnas.0609326103. PMC 1750896. PMID 17172448.
7. Rumbaugh G, Sia GM, Garner CC, Huganir RL (Jun 2003). "Synapse-associated protein-97 isoform-specific regulation of surface AMPA receptors and synaptic function in cultured neurons". The Journal of Neuroscience. 23 (11): 4567–76. PMID 12805297.
8. Xu S, Zhou F, Tao J, Song L, Ng SC, Wang X, Chen L, Yi F, Ran Z, Zhou R, Xia B (2014). "Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to Crohn's disease in a Chinese family study". PLOS ONE. 9 (6): e99807. doi:10.1371/journal.pone.0099807. PMC 4061034. PMID 24937328.
9. Lee S, Fan S, Makarova O, Straight S, Margolis B (Mar 2002). "A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia". Molecular and Cellular Biology. 22 (6): 1778–91. doi:10.1128/MCB.22.6.1778-1791.2002. PMC 135599. PMID 11865057.
10. Wu H, Nash JE, Zamorano P, Garner CC (Aug 2002). "Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications for AMPA receptor trafficking". The Journal of Biological Chemistry. 277 (34): 30928–34. doi:10.1074/jbc.M203735200. PMID 12050163.
11. Osterweil E, Wells DG, Mooseker MS (Jan 2005). "A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis". The Journal of Cell Biology. 168 (2): 329–38. doi:10.1083/jcb.200410091. PMC 2171578. PMID 15657400.
12. Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW (Jul 1998). "SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit". The Journal of Biological Chemistry. 273 (31): 19518–24. doi:10.1074/jbc.273.31.19518. PMID 9677374.
13. Cai C, Coleman SK, Niemi K, Keinänen K (Aug 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". The Journal of Biological Chemistry. 277 (35): 31484–90. doi:10.1074/jbc.M204354200. PMID 12070168.

Further reading

• Humbert P, Russell S, Richardson H (Jun 2003). "Dlg, Scribble and Lgl in cell polarity, cell proliferation and cancer". BioEssays. 25 (6): 542–53. doi:10.1002/bies.10286. PMID 12766944.
• Mukherjee A, Varma SK, Natarajan K (Feb 1972). "Ankle joint instability in poliomyelitis". Indian Journal of Pediatrics. 39 (289): 37–8. doi:10.1007/BF02799404. PMID 5024025.
• Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M (Nov 1995). "Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases". Nature. 378 (6552): 85–8. doi:10.1038/378085a0. PMID 7477295.
• Lue RA, Marfatia SM, Branton D, Chishti AH (Oct 1994). "Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1". Proceedings of the National Academy of Sciences of the United States of America. 91 (21): 9818–22. doi:10.1073/pnas.91.21.9818. PMC 44908. PMID 7937897.
• Niethammer M, Kim E, Sheng M (Apr 1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases". The Journal of Neuroscience. 16 (7): 2157–63. PMID 8601796.
• Azim AC, Knoll JH, Marfatia SM, Peel DJ, Bryant PJ, Chishti AH (Dec 1995). "DLG1: chromosome location of the closest human homologue of the Drosophila discs large tumor suppressor gene". Genomics. 30 (3): 613–6. doi:10.1006/geno.1995.1286. PMID 8825652.
• Lue RA, Brandin E, Chan EP, Branton D (Nov 1996). "Two independent domains of hDlg are sufficient for subcellular targeting: the PDZ1-2 conformational unit and an alternatively spliced domain". The Journal of Cell Biology. 135 (4): 1125–37. doi:10.1083/jcb.135.4.1125. PMC 2133382. PMID 8922391.
• 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". The Journal of Biological Chemistry. 272 (18): 11943–51. doi:10.1074/jbc.272.18.11943. PMID 9115257.
• Horio Y, Hibino H, Inanobe A, Yamada M, Ishii M, Tada Y, Satoh E, Hata Y, Takai Y, Kurachi Y (May 1997). "Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP90". The Journal of Biological Chemistry. 272 (20): 12885–8. doi:10.1074/jbc.272.20.12885. PMID 9148889.
• Lee SS, Weiss RS, Javier RT (Jun 1997). "Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein". Proceedings of the National Academy of Sciences of the United States of America. 94 (13): 6670–5. doi:10.1073/pnas.94.13.6670. PMC 21216. PMID 9192623.
• Satoh K, Yanai H, Senda T, Kohu K, Nakamura T, Okumura N, Matsumine A, Kobayashi S, Toyoshima K, Akiyama T (Jun 1997). "DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95". Genes to Cells. 2 (6): 415–24. doi:10.1046/j.1365-2443.1997.1310329.x. PMID 9286858.
• Hanada T, Lin L, Chandy KG, Oh SS, Chishti AH (Oct 1997). "Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytes". The Journal of Biological Chemistry. 272 (43): 26899–904. doi:10.1074/jbc.272.43.26899. PMID 9341123.
• Reuver SM, Garner CC (Apr 1998). "E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton". Journal of Cell Science. 111 (8): 1071–80. PMID 9512503.
• Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW (Jul 1998). "SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit". The Journal of Biological Chemistry. 273 (31): 19518–24. doi:10.1074/jbc.273.31.19518. PMID 9677374.
• Deguchi M, Hata Y, Takeuchi M, Ide N, Hirao K, Yao I, Irie M, Toyoda A, Takai Y (Oct 1998). "BEGAIN (brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein". The Journal of Biological Chemistry. 273 (41): 26269–72. doi:10.1074/jbc.273.41.26269. PMID 9756850.
• Brenman JE, Topinka JR, Cooper EC, McGee AW, Rosen J, Milroy T, Ralston HJ, Bredt DS (Nov 1998). "Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A". The Journal of Neuroscience. 18 (21): 8805–13. PMID 9786987.
• Bassand P, Bernard A, Rafiki A, Gayet D, Khrestchatisky M (Jun 1999). "Differential interaction of the tSXV motifs of the NR1 and NR2A NMDA receptor subunits with PSD-95 and SAP97". The European Journal of Neuroscience. 11 (6): 2031–43. doi:10.1046/j.1460-9568.1999.00611.x. PMID 10336672.
• Firestein BL, Firestein BL, Brenman JE, Aoki C, Sanchez-Perez AM, El-Husseini AE, Bredt DS (Nov 1999). "Cypin: a cytosolic regulator of PSD-95 postsynaptic targeting". Neuron. 24 (3): 659–72. doi:10.1016/S0896-6273(00)81120-4. PMID 10595517.
• Hibino H, Inanobe A, Tanemoto M, Fujita A, Doi K, Kubo T, Hata Y, Takai Y, Kurachi Y (Jan 2000). "Anchoring proteins confer G protein sensitivity to an inward-rectifier K(+) channel through the GK domain". The EMBO Journal. 19 (1): 78–83. doi:10.1093/emboj/19.1.78. PMC 1171779. PMID 10619846.
• Adey NB, Huang L, Ormonde PA, Baumgard ML, Pero R, Byreddy DV, Tavtigian SV, Bartel PL (Jan 2000). "Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding". Cancer Research. 60 (1): 35–7. PMID 10646847.

External links

• Drosophila discs large 1 - The Interactive Fly