DLG2

Disks large homolog 2 (DLG2) also known as channel-associated protein of synapse-110 (chapsyn-110) or postsynaptic density protein 93 (PSD-93) is a protein that in humans is encoded by the DLG2 gene.[5][6]

DLG2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2BYG, 2HE2
Identifiers
Aliases	DLG2, PPP1R58, PSD-93, PSD93, chapsyn-110, discs large homolog 2, discs large MAGUK scaffold protein 2
External IDs	OMIM: 603583 MGI: 1344351 HomoloGene: 1046 GeneCards: DLG2
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q14.1 Start 83,455,012 bp[1] End 85,627,922 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 E1|7 51.07 cM Start 90,476,672 bp[2] End 92,449,247 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • guanylate kinase activity • kinase binding • GO:0001948 protein binding • ionotropic glutamate receptor binding • Ras guanyl-nucleotide exchange factor activity • structural constituent of postsynaptic density Cellular component • postsynaptic membrane • cell projection • membrane • GO:0097483, GO:0097481 postsynaptic density • voltage-gated potassium channel complex • cell membrane • synapse • axon • cell junction • basolateral plasma membrane • ionotropic glutamate receptor complex • juxtaparanode region of axon • cytosol • neuromuscular junction • neuron projection • postsynaptic density membrane • glutamatergic synapse • axon cytoplasm Biological process • chemical synaptic transmission • receptor localization to synapse • negative regulation of phosphatase activity • receptor clustering • nervous system development • establishment or maintenance of epithelial cell apical/basal polarity • nociception • GDP metabolic process • GMP metabolic process • MAPK cascade • cellular response to potassium ion • cell-cell adhesion • maintenance of postsynaptic density structure • anterograde axonal protein transport • retrograde axonal protein transport • neurotransmitter receptor localization to postsynaptic specialization membrane • regulation of NMDA receptor activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1740	23859
Ensembl	ENSG00000150672	ENSMUSG00000052572
UniProt	Q15700	Q91XM9
RefSeq (mRNA)	NM_001142699 NM_001142700 NM_001142702 NM_001206769 NM_001300983 NM_001364 NM_001351274 NM_001351275 NM_001351276 NM_001377966 NM_001377967 NM_001377968 NM_001377970 NM_001377971 NM_001377972 NM_001377973 NM_001377974 NM_001377975 NM_001377976 NM_001377977 NM_001377978 NM_001377979 NM_001377980 NM_001377981 NM_001377982 NM_001377983	NM_001243046 NM_001243047 NM_011807
RefSeq (protein)	NP_001136171 NP_001136172 NP_001136174 NP_001193698 NP_001287912 NP_001355 NP_001338203 NP_001338204 NP_001338205 NP_001364895 NP_001364896 NP_001364897 NP_001364899 NP_001364900 NP_001364901 NP_001364902 NP_001364903 NP_001364904 NP_001364905 NP_001364906 NP_001364907 NP_001364908 NP_001364909 NP_001364910 NP_001364911 NP_001364912	NP_001229975 NP_001229976 NP_035937
Location (UCSC)	Chr 11: 83.46 – 85.63 Mb	Chr 7: 90.48 – 92.45 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Chapsyn-110/PSD-93 a member of the membrane-associated guanylate kinase (MAGUK) family. The protein forms a heterodimer with a related family member that may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Alternatively spliced transcript variants encoding distinct isoforms have been described but their full-length nature has yet to be completely determined.[7]

Model organisms

Dlg2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Abnormal[8]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Prepulse inhibition	Normal
Indirect calorimetry	Abnormal[9]
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal[10]
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[11]
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Abnormal[12]
All tests and analysis from[13][14]

Model organisms have been used in the study of DLG2 function. A knockout mouse line, called Dlg2^tm1Dsb was generated.[15][16] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][17] Twenty four tests were carried out on homozygous mutant mice and five significant abnormalities were observed.[13] Both sexes had atypical indirect calorimetry and DEXA parameters. Females also had decreased body weight, decreased circulating HDL cholesterol levels, and increased susceptibility to bacterial infection.[13]

Interactions

DLG2 has been shown to interact with GRIN2B,[18][19] KCNJ12.[20]

References

1. GRCh38: Ensembl release 89: ENSG00000150672 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000052572 - 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. Kim E, Cho KO, Rothschild A, Sheng M (December 1996). "Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins". Neuron. 17 (1): 103–13. doi:10.1016/S0896-6273(00)80284-6. PMID 8755482. S2CID 14852857.
6. Stathakis DG, Lee D, Bryant PJ (January 1999). "Fine-scale physical map of the 11q21 region surrounding the human DLG2 locus, the gene encoding Chapsyn-110". Genomics. 54 (1): 186–8. doi:10.1006/geno.1998.5527. PMID 9806853.
7. "Entrez Gene: DLG2 discs, large homolog 2, chapsyn-110 (Drosophila)".
8. "Body weight data for Dlg2". Wellcome Trust Sanger Institute.
9. "Indirect calorimetry data for Dlg2". Wellcome Trust Sanger Institute.
10. "DEXA data for Dlg2". Wellcome Trust Sanger Institute.
11. "Clinical chemistry data for Dlg2". Wellcome Trust Sanger Institute.
12. "Citrobacter infection data for Dlg2". Wellcome Trust Sanger Institute.
13. 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. S2CID 85911512.
14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
15. McGee AW, Topinka JR, Hashimoto K, Petralia RS, Kakizawa S, Kauer FW, Aguilera-Moreno A, Wenthold RJ, Kano M, Bredt DS, Kauer F (2001). "PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum". J. Neurosci. 21 (9): 3085–91. doi:10.1523/JNEUROSCI.21-09-03085.2001. PMC 6762564. PMID 11312293.
16. "Mouse Genome Informatics".
17. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
18. Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (June 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.
19. Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Südhof TC (September 1997). "Binding of neuroligins to PSD-95". Science. 277 (5331): 1511–5. doi:10.1126/science.277.5331.1511. PMID 9278515.
20. 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.

Further reading

• Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M (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. S2CID 4362906.
• Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS (1996). "Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains". Cell. 84 (5): 757–67. doi:10.1016/S0092-8674(00)81053-3. PMID 8625413. S2CID 15834673.
• Hsueh YP, Kim E, Sheng M (1997). "Disulfide-linked head-to-head multimerization in the mechanism of ion channel clustering by PSD-95". Neuron. 18 (5): 803–14. doi:10.1016/S0896-6273(00)80319-0. PMID 9182804. S2CID 18331544.
• Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg RJ, Craig AM, Sheng M (1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron. 20 (4): 693–707. doi:10.1016/S0896-6273(00)81009-0. PMID 9581762. S2CID 16068361.
• Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW (1998). "SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit". J. Biol. Chem. 273 (31): 19518–24. doi:10.1074/jbc.273.31.19518. PMID 9677374.
• 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. S2CID 12465062.
• Brenman JE, Topinka JR, Cooper EC, McGee AW, Rosen J, Milroy T, Ralston HJ, Bredt DS (1998). "Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A". J. Neurosci. 18 (21): 8805–13. doi:10.1523/JNEUROSCI.18-21-08805.1998. PMC 6793550. PMID 9786987.
• Craven SE, El-Husseini AE, Bredt DS (1999). "Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid and protein motifs". Neuron. 22 (3): 497–509. doi:10.1016/S0896-6273(00)80705-9. PMID 10197530.
• Sans N, Petralia RS, Wang YX, Blahos J, Hell JW, Wenthold RJ (2000). "A developmental change in NMDA receptor-associated proteins at hippocampal synapses". J. Neurosci. 20 (3): 1260–71. doi:10.1523/JNEUROSCI.20-03-01260.2000. PMC 6774158. PMID 10648730.
• 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, Blackstock WP, Grant SG (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. S2CID 14392630.
• Firestein BL, Craven SE, Bredt DS (2001). "Postsynaptic targeting of MAGUKs mediated by distinct N-terminal domains". NeuroReport. 11 (16): 3479–84. doi:10.1097/00001756-200011090-00016. PMID 11095503. S2CID 19718975.
• Haraguchi K, Satoh K, Yanai H, Hamada F, Kawabuchi M, Akiyama T (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. S2CID 37107139.
• 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.
• Weitzdoerfer R, Dierssen M, Fountoulakis M, Lubec G (2002). "Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure". J. Neural Transm. Suppl. (61): 59–70. doi:10.1007/978-3-7091-6262-0_5. ISBN 978-3-211-83704-7. PMID 11771761.