DLG4_RAT
ID DLG4_RAT Reviewed; 724 AA.
AC P31016; P97631;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Disks large homolog 4;
DE AltName: Full=Postsynaptic density protein 95 {ECO:0000305};
DE Short=PSD-95 {ECO:0000303|PubMed:20962234};
DE AltName: Full=Synapse-associated protein 90;
DE Short=SAP-90;
DE Short=SAP90;
GN Name=Dlg4 {ECO:0000312|RGD:68424};
GN Synonyms=Dlgh4, Psd95 {ECO:0000303|PubMed:27756895};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=1419001; DOI=10.1016/0896-6273(92)90245-9;
RA Cho K.-O., Hunt C.A., Kennedy M.B.;
RT "The rat brain postsynaptic density fraction contains a homolog of the
RT Drosophila discs-large tumor suppressor protein.";
RL Neuron 9:929-942(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7680343; DOI=10.1016/s0021-9258(18)53433-5;
RA Kistner U., Wenzel B.M., Veh R.W., Cases-Langhoff C., Garner A.M.,
RA Appeltauer U., Voss B., Gundelfinger E.D., Garner C.C.;
RT "SAP90, a rat presynaptic protein related to the product of the Drosophila
RT tumor suppressor gene dlg-A.";
RL J. Biol. Chem. 268:4580-4583(1993).
RN [3]
RP PROTEIN SEQUENCE OF 113-126; 212-233; 300-312; 381-399 AND 598-617, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Diao W.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 566-625.
RC STRAIN=Wistar Kyoto; TISSUE=Vascular smooth muscle;
RA Adams L.D., Werny I., Schwartz S.M.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH GRIN2A; GRIN2B; GRIN2C AND GRIN2D.
RX PubMed=7569905; DOI=10.1126/science.7569905;
RA Kornau H.C., Schenker L.T., Kennedy M.B., Seeburg P.H.;
RT "Domain interaction between NMDA receptor subunits and the postsynaptic
RT density protein PSD-95.";
RL Science 269:1737-1740(1995).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=8922396; DOI=10.1523/jneurosci.16-23-07407.1996;
RA Brenman J.E., Christopherson K.S., Craven S.E., McGee A.W., Bredt D.S.;
RT "Cloning and characterization of postsynaptic density 93, a nitric oxide
RT synthase interacting protein.";
RL J. Neurosci. 16:7407-7415(1996).
RN [7]
RP INTERACTION WITH DLGAP1; DLGAP2; DLGAP3 AND DLGAP4, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=9115257; DOI=10.1074/jbc.272.18.11943;
RA Takeuchi M., Hata Y., Hirao K., Toyoda A., Irie M., Takai Y.;
RT "SAPAPs. A family of PSD-95/SAP90-associated proteins localized at
RT postsynaptic density.";
RL J. Biol. Chem. 272:11943-11951(1997).
RN [8]
RP INTERACTION WITH BEGAIN AND DLGAP1.
RX PubMed=9756850; DOI=10.1074/jbc.273.41.26269;
RA Deguchi M., Hata Y., Takeuchi M., Ide N., Hirao K., Yao I., Irie M.,
RA Toyoda A., Takai Y.;
RT "BEGAIN (brain-enriched guanylate kinase-associated protein), a novel
RT neuronal PSD-95/SAP90-binding protein.";
RL J. Biol. Chem. 273:26269-26272(1998).
RN [9]
RP INTERACTION WITH MAP1A.
RX PubMed=9786987; DOI=10.1523/jneurosci.18-21-08805.1998;
RA Brenman J.E., Topinka J.R., Cooper E.C., McGee A.W., Rosen J., Milroy T.,
RA Ralston H.J., Bredt D.S.;
RT "Localization of postsynaptic density-93 to dendritic microtubules and
RT interaction with microtubule-associated protein 1A.";
RL J. Neurosci. 18:8805-8813(1998).
RN [10]
RP INTERACTION WITH SYNGAP1.
RX PubMed=9581761; DOI=10.1016/s0896-6273(00)81008-9;
RA Kim J.H., Liao D., Lau L.-F., Huganir R.L.;
RT "SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein
RT family.";
RL Neuron 20:683-691(1998).
RN [11]
RP INTERACTION WITH CRIPT.
RX PubMed=9581762; DOI=10.1016/s0896-6273(00)81009-0;
RA Niethammer M., Valtschanoff J.G., Kapoor T.M., Allison D.W., Weinberg R.J.,
RA Craig A.M., Sheng M.;
RT "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of
RT PSD-95/SAP90.";
RL Neuron 20:693-707(1998).
RN [12]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-3 AND CYS-5, AND PALMITOYLATION AT
RP CYS-3 AND CYS-5.
RX PubMed=10629226; DOI=10.1083/jcb.148.1.159;
RA El-Husseini A.E., Craven S.E., Chetkovich D.M., Firestein B.L., Schnell E.,
RA Aoki C., Bredt D.S.;
RT "Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting,
RT postsynaptic targeting, and ion channel clustering.";
RL J. Cell Biol. 148:159-172(2000).
RN [13]
RP INTERACTION WITH SEMA4C.
RX PubMed=11134026; DOI=10.1074/jbc.m009051200;
RA Inagaki S., Ohoka Y., Sugimoto H., Fujioka S., Amazaki M., Kurinami H.,
RA Miyazaki N., Tohyama M., Furuyama T.;
RT "Sema4c, a transmembrane semaphorin, interacts with a post-synaptic density
RT protein, PSD-95.";
RL J. Biol. Chem. 276:9174-9181(2001).
RN [14]
RP INTERACTION WITH SEMA4F, AND SUBCELLULAR LOCATION.
RX PubMed=11483650; DOI=10.1046/j.1471-4159.2001.00447.x;
RA Schultze W., Eulenburg V., Lessmann V., Herrmann L., Dittmar T.,
RA Gundelfinger E.D., Heumann R., Erdmann K.S.;
RT "Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95.";
RL J. Neurochem. 78:482-489(2001).
RN [15]
RP INTERACTION WITH SIPA1L1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11502259; DOI=10.1016/s0896-6273(01)00355-5;
RA Pak D.T., Yang S., Rudolph-Correia S., Kim E., Sheng M.;
RT "Regulation of dendritic spine morphology by SPAR, a PSD-95-associated
RT RapGAP.";
RL Neuron 31:289-303(2001).
RN [16]
RP INTERACTION WITH KCND2.
RX PubMed=11923279; DOI=10.1074/jbc.m109412200;
RA Wong W., Newell E.W., Jugloff D.G.M., Jones O.T., Schlichter L.C.;
RT "Cell surface targeting and clustering interactions between heterologously
RT expressed PSD-95 and the Shal voltage-gated potassium channel, Kv4.2.";
RL J. Biol. Chem. 277:20423-20430(2002).
RN [17]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=12151521; DOI=10.1523/jneurosci.22-15-06415.2002;
RA Chetkovich D.M., Bunn R.C., Kuo S.-H., Kawasaki Y., Kohwi M., Bredt D.S.;
RT "Postsynaptic targeting of alternative postsynaptic density-95 isoforms by
RT distinct mechanisms.";
RL J. Neurosci. 22:6415-6425(2002).
RN [18]
RP INTERACTION WITH KCNJ4, AND SUBCELLULAR LOCATION.
RX PubMed=11997254; DOI=10.1152/ajpcell.00615.2001;
RA Inanobe A., Fujita A., Ito M., Tomoike H., Inageda K., Kurachi Y.;
RT "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic
RT membrane of excitatory synapses.";
RL Am. J. Physiol. 282:C1396-C1403(2002).
RN [19]
RP SUBCELLULAR LOCATION, UBIQUITINATION, AND MUTAGENESIS OF 13-ARG--HIS-24.
RX PubMed=14642282; DOI=10.1016/s0896-6273(03)00687-1;
RA Colledge M., Snyder E.M., Crozier R.A., Soderling J.A., Jin Y.,
RA Langeberg L.K., Lu H., Bear M.F., Scott J.D.;
RT "Ubiquitination regulates PSD-95 degradation and AMPA receptor surface
RT expression.";
RL Neuron 40:595-607(2003).
RN [20]
RP INTERACTION WITH ASIC3, AND FUNCTION.
RX PubMed=15317815; DOI=10.1074/jbc.m405874200;
RA Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J.;
RT "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have
RT opposite effects on H+- gated current.";
RL J. Biol. Chem. 279:46962-46968(2004).
RN [21]
RP INTERACTION WITH CXADR.
RX PubMed=15304526; DOI=10.1242/jcs.01300;
RA Ashbourne-Excoffon K.J.D., Hruska-Hageman A.M., Klotz M., Traver G.L.,
RA Zabner J.;
RT "A role for the PDZ-binding domain of the coxsackie B virus and adenovirus
RT receptor (CAR) in cell adhesion and growth.";
RL J. Cell Sci. 117:4401-4409(2004).
RN [22]
RP PALMITOYLATION.
RX PubMed=15603741; DOI=10.1016/j.neuron.2004.12.005;
RA Fukata M., Fukata Y., Adesnik H., Nicoll R.A., Bredt D.S.;
RT "Identification of PSD-95 palmitoylating enzymes.";
RL Neuron 44:987-996(2004).
RN [23]
RP FUNCTION.
RX PubMed=15358863; DOI=10.1073/pnas.0405939101;
RA Prange O., Wong T.P., Gerrow K., Wang Y.T., El-Husseini A.;
RT "A balance between excitatory and inhibitory synapses is controlled by PSD-
RT 95 and neuroligin.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:13915-13920(2004).
RN [24]
RP INTERACTION WITH PRR7.
RX PubMed=15629447; DOI=10.1016/j.bbrc.2004.11.154;
RA Murata Y., Doi T., Taniguchi H., Fujiyoshi Y.;
RT "Proteomic analysis revealed a novel synaptic proline-rich membrane protein
RT (PRR7) associated with PSD-95 and NMDA receptor.";
RL Biochem. Biophys. Res. Commun. 327:183-191(2005).
RN [25]
RP INTERACTION WITH KLHL17.
RX PubMed=16054660; DOI=10.1016/j.neuropharm.2005.05.022;
RA Chen Y., Li M.;
RT "Interactions between CAP70 and actinfilin are important for integrity of
RT actin cytoskeleton structures in neurons.";
RL Neuropharmacology 49:1026-1041(2005).
RN [26]
RP INTERACTION WITH LRFN2.
RX PubMed=16495444; DOI=10.1523/jneurosci.3799-05.2006;
RA Wang C.Y., Chang K., Petralia R.S., Wang Y.X., Seabold G.K., Wenthold R.J.;
RT "A novel family of adhesion-like molecules that interacts with the NMDA
RT receptor.";
RL J. Neurosci. 26:2174-2183(2006).
RN [27]
RP INTERACTION WITH LRFN1.
RX PubMed=16630835; DOI=10.1016/j.neuron.2006.04.005;
RA Ko J., Kim S., Chung H.S., Kim K., Han K., Kim H., Jun H., Kaang B.-K.,
RA Kim E.;
RT "SALM synaptic cell adhesion-like molecules regulate the differentiation of
RT excitatory synapses.";
RL Neuron 50:233-245(2006).
RN [28]
RP INTERACTION WITH ADAM22 AND LGI1.
RX PubMed=16990550; DOI=10.1126/science.1129947;
RA Fukata Y., Adesnik H., Iwanaga T., Bredt D.S., Nicoll R.A., Fukata M.;
RT "Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic
RT transmission.";
RL Science 313:1792-1795(2006).
RN [29]
RP INTERACTION WITH ANKS1B.
RX PubMed=17334360; DOI=10.1038/nn1867;
RA Jordan B.A., Fernholz B.D., Khatri L., Ziff E.B.;
RT "Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers
RT and protein synthesis in neurons.";
RL Nat. Neurosci. 10:427-435(2007).
RN [30]
RP INTERACTION WITH FRMPD4.
RX PubMed=19118189; DOI=10.1523/jneurosci.3112-08.2008;
RA Lee H.W., Choi J., Shin H., Kim K., Yang J., Na M., Choi S.Y., Kang G.B.,
RA Eom S.H., Kim H., Kim E.;
RT "Preso, a novel PSD-95-interacting FERM and PDZ domain protein that
RT regulates dendritic spine morphogenesis.";
RL J. Neurosci. 28:14546-14556(2008).
RN [31]
RP FUNCTION, SUBCELLULAR LOCATION, AND PALMITOYLATION BY ZDHHC2.
RX PubMed=19596852; DOI=10.1083/jcb.200903101;
RA Noritake J., Fukata Y., Iwanaga T., Hosomi N., Tsutsumi R., Matsuda N.,
RA Tani H., Iwanari H., Mochizuki Y., Kodama T., Matsuura Y., Bredt D.S.,
RA Hamakubo T., Fukata M.;
RT "Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic
RT targeting of PSD-95.";
RL J. Cell Biol. 186:147-160(2009).
RN [32]
RP INTERACTION WITH ABR AND BCR, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=20962234; DOI=10.1523/jneurosci.1711-10.2010;
RA Oh D., Han S., Seo J., Lee J.R., Choi J., Groffen J., Kim K., Cho Y.S.,
RA Choi H.S., Shin H., Woo J., Won H., Park S.K., Kim S.Y., Jo J.,
RA Whitcomb D.J., Cho K., Kim H., Bae Y.C., Heisterkamp N., Choi S.Y., Kim E.;
RT "Regulation of synaptic Rac1 activity, long-term potentiation maintenance,
RT and learning and memory by BCR and ABR Rac GTPase-activating proteins.";
RL J. Neurosci. 30:14134-14144(2010).
RN [33]
RP INTERACTION WITH ADAM22, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND TISSUE SPECIFICITY.
RX PubMed=20089912; DOI=10.1523/jneurosci.4661-09.2010;
RA Ogawa Y., Oses-Prieto J., Kim M.Y., Horresh I., Peles E., Burlingame A.L.,
RA Trimmer J.S., Meijer D., Rasband M.N.;
RT "ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated
RT guanylate kinases to juxtaparanodes of myelinated axons.";
RL J. Neurosci. 30:1038-1048(2010).
RN [34]
RP INTERACTION WITH DGKI.
RX PubMed=21119615; DOI=10.1038/emboj.2010.286;
RA Yang J., Seo J., Nair R., Han S., Jang S., Kim K., Han K., Paik S.K.,
RA Choi J., Lee S., Bae Y.C., Topham M.K., Prescott S.M., Rhee J.S.,
RA Choi S.Y., Kim E.;
RT "DGKiota regulates presynaptic release during mGluR-dependent LTD.";
RL EMBO J. 30:165-180(2011).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240; SER-295; SER-418;
RP THR-420; SER-422; SER-449 AND SER-654, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [36]
RP FUNCTION, AND INTERACTION WITH GPER1 AND NOS1.
RX PubMed=23300088; DOI=10.1074/jbc.m112.412478;
RA Akama K.T., Thompson L.I., Milner T.A., McEwen B.S.;
RT "Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled
RT receptor 30 (GPR30), an estrogen receptor that can be identified in
RT hippocampal dendritic spines.";
RL J. Biol. Chem. 288:6438-6450(2013).
RN [37]
RP FUNCTION, INTERACTION WITH GRIN2A AND RPH3A, AND SUBCELLULAR LOCATION.
RX PubMed=26679993; DOI=10.1038/ncomms10181;
RA Stanic J., Carta M., Eberini I., Pelucchi S., Marcello E., Genazzani A.A.,
RA Racca C., Mulle C., Di Luca M., Gardoni F.;
RT "Rabphilin 3A retains NMDA receptors at synaptic sites through interaction
RT with GluN2A/PSD-95 complex.";
RL Nat. Commun. 6:10181-10181(2015).
RN [38]
RP IDENTIFICATION IN A COMPLEX WITH PRR7 AND GRIN1, AND INTERACTION WITH PRR7.
RX PubMed=27458189; DOI=10.15252/embj.201593070;
RA Kravchick D.O., Karpova A., Hrdinka M., Lopez-Rojas J., Iacobas S.,
RA Carbonell A.U., Iacobas D.A., Kreutz M.R., Jordan B.A.;
RT "Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates
RT NMDA-mediated excitotoxicity.";
RL EMBO J. 35:1923-1934(2016).
RN [39]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PALMITOYLATION AT CYS-3 AND
RP CYS-5, AND MUTAGENESIS OF CYS-3 AND CYS-5.
RX PubMed=27307232; DOI=10.1523/jneurosci.0419-16.2016;
RA Yokoi N., Fukata Y., Sekiya A., Murakami T., Kobayashi K., Fukata M.;
RT "Identification of PSD-95 Depalmitoylating Enzymes.";
RL J. Neurosci. 36:6431-6444(2016).
RN [40]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH CACNG2 AND
RP MPP2.
RX PubMed=27756895; DOI=10.1038/srep35283;
RA Rademacher N., Schmerl B., Lardong J.A., Wahl M.C., Shoichet S.A.;
RT "MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell
RT adhesion molecules to core components of the postsynaptic density.";
RL Sci. Rep. 6:35283-35283(2016).
RN [41]
RP SUBCELLULAR LOCATION.
RX PubMed=30021165; DOI=10.1016/j.celrep.2018.06.071;
RA Stucchi R., Plucinska G., Hummel J.J.A., Zahavi E.E., Guerra San Juan I.,
RA Klykov O., Scheltema R.A., Altelaar A.F.M., Hoogenraad C.C.;
RT "Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls
RT DCV Binding and Liprin-alpha/TANC2 Recruits DCVs to Postsynaptic Sites.";
RL Cell Rep. 24:685-700(2018).
RN [42]
RP PALMITOYLATION.
RX PubMed=31189538; DOI=10.1242/jcs.230052;
RA Shah B.S., Shimell J.J., Bamji S.X.;
RT "Regulation of dendrite morphology and excitatory synapse formation by
RT zDHHC15.";
RL J. Cell Sci. 132:0-0(2019).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 302-402.
RX PubMed=8674113; DOI=10.1016/s0092-8674(00)81307-0;
RA Doyle D.A., Lee A., Lewis J., Kim E., Sheng M., Mackinnon R.;
RT "Crystal structures of a complexed and peptide-free membrane protein-
RT binding domain: molecular basis of peptide recognition by PDZ.";
RL Cell 85:1067-1076(1996).
RN [44]
RP STRUCTURE BY NMR OF 155-246, AND INTERACTION WITH NOS1 AND CAPON.
RX PubMed=10623522; DOI=10.1006/jmbi.1999.3350;
RA Tochio H., Hung F., Li M., Bredt D.S., Zhang M.;
RT "Solution structure and backbone dynamics of the second PDZ domain of
RT postsynaptic density-95.";
RL J. Mol. Biol. 295:225-237(2000).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 430-724.
RX PubMed=11779504; DOI=10.1016/s1097-2765(01)00411-7;
RA McGee A.W., Dakoji S.R., Olsen O., Bredt D.S., Lim W.A., Prehoda K.E.;
RT "Structure of the SH3-guanylate kinase module from PSD-95 suggests a
RT mechanism for regulated assembly of MAGUK scaffolding proteins.";
RL Mol. Cell 8:1291-1301(2001).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 430-724.
RX PubMed=11779506; DOI=10.1016/s1097-2765(01)00416-6;
RA Tavares G.A., Panepucci E.H., Brunger A.T.;
RT "Structural characterization of the intramolecular interaction between the
RT SH3 and guanylate kinase domains of PSD-95.";
RL Mol. Cell 8:1313-1325(2001).
RN [47]
RP STRUCTURE BY NMR OF 62-154 IN COMPLEX WITH CYCLIC PEPTIDE.
RX PubMed=15123241; DOI=10.1016/j.chembiol.2004.03.013;
RA Piserchio A., Salinas G.D., Li T., Marshall J., Spaller M.R., Mierke D.F.;
RT "Targeting specific PDZ domains of PSD-95; structural basis for enhanced
RT affinity and enzymatic stability of a cyclic peptide.";
RL Chem. Biol. 11:469-473(2004).
RN [48]
RP STRUCTURE BY NMR OF 61-249 IN COMPLEX WITH PEPTIDE.
RX PubMed=19072119; DOI=10.1021/ja8076022;
RA Wang W., Weng J., Zhang X., Liu M., Zhang M.;
RT "Creating conformational entropy by increasing interdomain mobility in
RT ligand binding regulation: a revisit to N-terminal tandem PDZ domains of
RT PSD-95.";
RL J. Am. Chem. Soc. 131:787-796(2009).
CC -!- FUNCTION: Postsynaptic scaffolding protein that plays a critical role
CC in synaptogenesis and synaptic plasticity by providing a platform for
CC the postsynaptic clustering of crucial synaptic proteins
CC (PubMed:15317815, PubMed:15358863, PubMed:19596852, PubMed:23300088,
CC PubMed:26679993). Interacts with the cytoplasmic tail of NMDA receptor
CC subunits and shaker-type potassium channels. Required for synaptic
CC plasticity associated with NMDA receptor signaling. Overexpression or
CC depletion of DLG4 changes the ratio of excitatory to inhibitory
CC synapses in hippocampal neurons. May reduce the amplitude of ASIC3
CC acid-evoked currents by retaining the channel intracellularly. May
CC regulate the intracellular trafficking of ADR1B (By similarity). Also
CC regulates AMPA-type glutamate receptor (AMPAR) immobilization at
CC postsynaptic density keeping the channels in an activated state in the
CC presence of glutamate and preventing synaptic depression
CC (PubMed:19596852).Under basal conditions, cooperates with FYN to
CC stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through
CC FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of
CC association with endocytic proteins (By similarity).
CC {ECO:0000250|UniProtKB:P78352, ECO:0000250|UniProtKB:Q62108,
CC ECO:0000269|PubMed:15317815, ECO:0000269|PubMed:15358863,
CC ECO:0000269|PubMed:19596852, ECO:0000269|PubMed:23300088,
CC ECO:0000269|PubMed:26679993}.
CC -!- SUBUNIT: Interacts through its PDZ domains with ANO2 and NETO1 (By
CC similarity). Interacts with KCNJ4 (PubMed:11997254). Interacts through
CC its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C and GRIN2D
CC (PubMed:7569905). Interacts with ERBB4 (By similarity). Interacts with
CC KCNA1, KCNA2, KCNA3 and KCNA4 (By similarity). Interacts with LRRC4 and
CC LRRC4B (By similarity). Interacts with SYNGAP1 (PubMed:9581761).
CC Interacts with ASIC3 (PubMed:15317815). Interacts with SEMA4C
CC (PubMed:11134026). Interacts with CXADR (PubMed:15304526). Interacts
CC with KCND2 (PubMed:11923279). Interacts (via first PDZ domain) with
CC CRIPT (PubMed:9581762). Interacts through its first PDZ domain with
CC GRIK2 and KCNA4 (By similarity). Interacts through its second PDZ
CC domain with the PDZ domain of NOS1 or the C-terminus of CAPON
CC (PubMed:23300088). Interacts through its third PDZ domain with NLGN1
CC and CRIPT, and probably with NLGN2 and NLGN3 (By similarity). Interacts
CC through its guanylate kinase-like domain with DLGAP1/GKAP, DLGAP2,
CC DLGAP3, DLGAP4, MAP1A, BEGAIN and SIPA1L1 (PubMed:9115257,
CC PubMed:9756850, PubMed:11502259, PubMed:9786987). Interacts through its
CC guanylate kinase-like domain with KIF13B (By similarity). Isoform 2
CC interacts through an L27 domain with HGS/HRS and the first L27 domain
CC of CASK (By similarity). Interacts with ANKS1B (PubMed:17334360).
CC Interacts with ADR1B (By similarity). May interact with HTR2A (By
CC similarity). Interacts with ADAM22, KLHL17 and LGI1 (PubMed:16054660,
CC PubMed:16990550, PubMed:20089912). Interacts with FRMPD4 (via C-
CC terminus) (PubMed:19118189). Interacts with LRFN1 and LRFN2
CC (PubMed:16495444, PubMed:16630835). Interacts with LRFN4 (By
CC similarity). Interacts (via N-terminal tandem pair of PDZ domains) with
CC GPER1 (via C-terminus tail motif); the interaction is direct and
CC induces the increase of GPER1 protein levels residing at the plasma
CC membrane surface in a estradiol-independent manner (PubMed:23300088).
CC Interacts (via N-terminus tandem pair of PDZ domains) with NOS1 (via N-
CC terminal domain) (PubMed:23300088). Interacts with SHANK3 (By
CC similarity). Interacts with GPR85 (By similarity). Interacts with
CC CACNG2 and MPP2 (via the SH3-Guanylate kinase-like sub-module)
CC (PubMed:27756895). Interacts with ADGRB1 (By similarity). Found in a
CC complex with PRR7 and GRIN1 (PubMed:27458189). Interacts (via PDZ3
CC domain and to lesser degree via PDZ2 domain) with PRR7
CC (PubMed:27458189, PubMed:15629447). Component of the postsynaptic
CC hippocampal AMPA-type glutamate receptor (AMPAR) complex, at least
CC composed of pore forming AMPAR subunits GRIA1, GRIA2 and GRIA3 and
CC AMPAR auxiliary proteins SHISA6 and SHISA7. Interacts (via its first
CC two PDZ domains) with SHISA6 and SHISA7 (via PDZ-binding motif); the
CC interaction is direct (By similarity). Interacts (via PDZ domain 2)
CC with SEMA4F (via PDZ-binding motif); this interaction may promote
CC translocation of DLG4/SAP90 to the membrane (PubMed:11483650).
CC Interacts with RPH3A and GRIN2A; this ternary complex regulates NMDA
CC receptor composition at postsynaptic membranes (PubMed:26679993).
CC Interacts with ABR and BCR (PubMed:20962234). Interacts with DGKI (via
CC PDZ-binding motif); controls the localization of DGKI to the synapse
CC (PubMed:21119615). Interacts with C9orf72, SMCR8 and RAB39B (By
CC similarity). Interacts with ZDHHC5 (By similarity).
CC {ECO:0000250|UniProtKB:P78352, ECO:0000250|UniProtKB:Q62108,
CC ECO:0000269|PubMed:11134026, ECO:0000269|PubMed:11483650,
CC ECO:0000269|PubMed:11502259, ECO:0000269|PubMed:11923279,
CC ECO:0000269|PubMed:11997254, ECO:0000269|PubMed:14642282,
CC ECO:0000269|PubMed:15304526, ECO:0000269|PubMed:15317815,
CC ECO:0000269|PubMed:15629447, ECO:0000269|PubMed:16054660,
CC ECO:0000269|PubMed:16495444, ECO:0000269|PubMed:16630835,
CC ECO:0000269|PubMed:16990550, ECO:0000269|PubMed:17334360,
CC ECO:0000269|PubMed:19118189, ECO:0000269|PubMed:20089912,
CC ECO:0000269|PubMed:20962234, ECO:0000269|PubMed:21119615,
CC ECO:0000269|PubMed:23300088, ECO:0000269|PubMed:26679993,
CC ECO:0000269|PubMed:27458189, ECO:0000269|PubMed:27756895,
CC ECO:0000269|PubMed:7569905, ECO:0000269|PubMed:9115257,
CC ECO:0000269|PubMed:9581761, ECO:0000269|PubMed:9581762,
CC ECO:0000269|PubMed:9756850, ECO:0000269|PubMed:9786987}.
CC -!- INTERACTION:
CC P31016; P10608: Adrb2; NbExp=2; IntAct=EBI-375655, EBI-7090342;
CC P31016; P70478: Apc; NbExp=2; IntAct=EBI-375655, EBI-631663;
CC P31016; Q71RJ2: Cacng2; NbExp=2; IntAct=EBI-375655, EBI-8538384;
CC P31016; Q9Z1T4: Cnksr2; NbExp=4; IntAct=EBI-375655, EBI-8548356;
CC P31016; F1MAB7: Dgki; NbExp=5; IntAct=EBI-375655, EBI-8523614;
CC P31016; O08560: Dgkz; NbExp=6; IntAct=EBI-375655, EBI-8570505;
CC P31016; Q62696: Dlg1; NbExp=2; IntAct=EBI-375655, EBI-389325;
CC P31016; P97836: Dlgap1; NbExp=9; IntAct=EBI-375655, EBI-80901;
CC P31016; P97837: Dlgap2; NbExp=2; IntAct=EBI-375655, EBI-81025;
CC P31016; P19490: Gria1; NbExp=5; IntAct=EBI-375655, EBI-371642;
CC P31016; P35439: Grin1; NbExp=4; IntAct=EBI-375655, EBI-877897;
CC P31016; Q00959: Grin2a; NbExp=5; IntAct=EBI-375655, EBI-630970;
CC P31016; Q00960: Grin2b; NbExp=8; IntAct=EBI-375655, EBI-396905;
CC P31016; Q9WVI4: Gucy1a2; NbExp=7; IntAct=EBI-375655, EBI-7665590;
CC P31016; P20595: Gucy1b1; NbExp=2; IntAct=EBI-375655, EBI-7980539;
CC P31016; Q5XIE8: Itm2b; NbExp=5; IntAct=EBI-375655, EBI-15348306;
CC P31016; Q8K430: Klhl17; NbExp=2; IntAct=EBI-375655, EBI-7713653;
CC P31016; Q460M5: Lrfn2; NbExp=3; IntAct=EBI-375655, EBI-877185;
CC P31016; P70587: Lrrc7; NbExp=5; IntAct=EBI-375655, EBI-7798464;
CC P31016; P34926: Map1a; NbExp=16; IntAct=EBI-375655, EBI-631571;
CC P31016; O54857: Pten; NbExp=5; IntAct=EBI-375655, EBI-8074312;
CC P31016; Q9WV48: Shank1; NbExp=3; IntAct=EBI-375655, EBI-80909;
CC P31016; P28572: Slc6a9; NbExp=2; IntAct=EBI-375655, EBI-848783;
CC P31016; P28572-2: Slc6a9; NbExp=4; IntAct=EBI-375655, EBI-848796;
CC P31016; P30937: Sstr4; NbExp=3; IntAct=EBI-375655, EBI-7665959;
CC P31016; Q9QUH6: Syngap1; NbExp=3; IntAct=EBI-375655, EBI-2310349;
CC P31016; Q8R4T5: Tamalin; NbExp=3; IntAct=EBI-375655, EBI-7361884;
CC P31016; Q6IN36: Wipf1; NbExp=5; IntAct=EBI-375655, EBI-6986245;
CC P31016; P08588: ADRB1; Xeno; NbExp=2; IntAct=EBI-375655, EBI-991009;
CC P31016; Q9P021: CRIPT; Xeno; NbExp=2; IntAct=EBI-375655, EBI-946968;
CC P31016; Q12959-2: DLG1; Xeno; NbExp=9; IntAct=EBI-375655, EBI-357500;
CC P31016; Q12879: GRIN2A; Xeno; NbExp=2; IntAct=EBI-375655, EBI-7249937;
CC P31016; Q13224: GRIN2B; Xeno; NbExp=2; IntAct=EBI-375655, EBI-2256942;
CC P31016; Q14957: GRIN2C; Xeno; NbExp=2; IntAct=EBI-375655, EBI-8285963;
CC P31016; P22459: KCNA4; Xeno; NbExp=3; IntAct=EBI-375655, EBI-631235;
CC P31016; P05480: Src; Xeno; NbExp=9; IntAct=EBI-375655, EBI-298680;
CC P31016; Q80Z96: Vangl1; Xeno; NbExp=4; IntAct=EBI-375655, EBI-1750708;
CC P31016; Q91ZD4: Vangl2; Xeno; NbExp=6; IntAct=EBI-375655, EBI-1750744;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10629226,
CC ECO:0000269|PubMed:14642282, ECO:0000269|PubMed:9115257,
CC ECO:0000305|PubMed:11997254}; Lipid-anchor
CC {ECO:0000269|PubMed:10629226}; Cytoplasmic side
CC {ECO:0000269|PubMed:10629226}. Postsynaptic density
CC {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:11483650,
CC ECO:0000269|PubMed:26679993, ECO:0000269|PubMed:27307232,
CC ECO:0000269|PubMed:27756895, ECO:0000269|PubMed:9115257}. Synapse
CC {ECO:0000269|PubMed:11483650, ECO:0000269|PubMed:11502259,
CC ECO:0000269|PubMed:14642282, ECO:0000269|PubMed:19596852,
CC ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20962234,
CC ECO:0000269|PubMed:27307232, ECO:0000269|PubMed:8922396,
CC ECO:0000269|PubMed:9115257}. Cytoplasm {ECO:0000269|PubMed:9115257}.
CC Cell projection, axon {ECO:0000269|PubMed:20089912,
CC ECO:0000269|PubMed:8922396}. Cell projection, dendritic spine
CC {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:26679993,
CC ECO:0000269|PubMed:30021165}. Cell projection, dendrite
CC {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:11483650}. Presynapse
CC {ECO:0000269|PubMed:8922396}. Note=High levels in postsynaptic density
CC of neurons in the forebrain. Also in presynaptic region of inhibitory
CC synapses formed by cerebellar basket cells on axon hillocks of Purkinje
CC cells. Suppression of neuronal activity induces synaptic accumulation
CC and clustering of DLG4 (PubMed:19596852). {ECO:0000269|PubMed:19596852,
CC ECO:0000269|PubMed:8922396}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PSD95-alpha;
CC IsoId=P31016-1; Sequence=Displayed;
CC Name=2; Synonyms=PSD95-beta;
CC IsoId=P31016-2; Sequence=Not described;
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level)
CC (PubMed:12151521, PubMed:27307232, PubMed:20962234). Detected in
CC juxtaparanodal zones in the central nervous system and at nerve
CC terminal plexuses of basket cells in the cerebellum (PubMed:20089912).
CC Expressed in cerebrum (PubMed:27307232). Expressed in hippocampal
CC neurons (at protein level) (PubMed:11502259, PubMed:12151521,
CC PubMed:27307232, PubMed:27756895). Isoform 1 and isoform 2: highly
CC expressed in cerebellum, cortex, hippocampus, and corpus striatum
CC (PubMed:12151521, PubMed:20962234). {ECO:0000269|PubMed:11502259,
CC ECO:0000269|PubMed:12151521, ECO:0000269|PubMed:20089912,
CC ECO:0000269|PubMed:20962234, ECO:0000269|PubMed:27307232,
CC ECO:0000269|PubMed:27756895}.
CC -!- DEVELOPMENTAL STAGE: Expression gradually increases from late embryonic
CC (E18) stage until adulthood. {ECO:0000269|PubMed:20962234}.
CC -!- DOMAIN: The PDZ domain 3 mediates interaction with ADR1B.
CC {ECO:0000250}.
CC -!- DOMAIN: The L27 domain near the N-terminus of isoform 2 is required for
CC HGS/HRS-dependent targeting to postsynaptic density. {ECO:0000250}.
CC -!- PTM: Palmitoylated (PubMed:10629226, PubMed:27307232). Palmitoylation
CC is required for targeting to postsynaptic density, plasma membrane and
CC synapses (PubMed:10629226, PubMed:27307232). Palmitoylation by ZDHHC2
CC occurs when the synaptic activity decreases and induces DLG4 synaptic
CC clustering (PubMed:19596852). Palmitoylation by ZDHHC15 regulates
CC trafficking to the postsynaptic density and function in synaptogenesis
CC (PubMed:15603741, PubMed:31189538). Palmitoylation may play a role in
CC glutamate receptor GRIA1 synapse clustering (PubMed:27307232).
CC Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by
CC ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2 (PubMed:27307232). Undergoes
CC rapid synaptic palmitoylation/depalmitoylation cycle during neuronal
CC development which slows down in mature neurons (PubMed:27307232).
CC {ECO:0000269|PubMed:10629226, ECO:0000269|PubMed:15603741,
CC ECO:0000269|PubMed:19596852, ECO:0000269|PubMed:27307232,
CC ECO:0000269|PubMed:31189538}.
CC -!- PTM: Ubiquitinated by MDM2 in response to NMDA receptor activation,
CC leading to proteasome-mediated degradation of DLG4 which is required
CC for AMPA receptor endocytosis. {ECO:0000269|PubMed:14642282}.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
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DR EMBL; M96853; AAA41971.1; -; mRNA.
DR EMBL; X66474; CAA47103.1; -; mRNA.
DR EMBL; U77090; AAB38270.1; -; mRNA.
DR PIR; A45436; A45436.
DR PIR; JH0800; JH0800.
DR RefSeq; NP_062567.1; NM_019621.1. [P31016-1]
DR PDB; 1BE9; X-ray; 1.82 A; A=302-430.
DR PDB; 1BFE; X-ray; 2.30 A; A=302-402.
DR PDB; 1IU0; NMR; -; A=61-151.
DR PDB; 1IU2; NMR; -; A=61-151.
DR PDB; 1JXM; X-ray; 2.00 A; A=430-724.
DR PDB; 1JXO; X-ray; 2.30 A; A/B=430-724.
DR PDB; 1KJW; X-ray; 1.80 A; A=430-724.
DR PDB; 1QLC; NMR; -; A=155-249.
DR PDB; 1RGR; NMR; -; A=62-154.
DR PDB; 1TP3; X-ray; 1.99 A; A=302-402.
DR PDB; 1TP5; X-ray; 1.54 A; A=302-402.
DR PDB; 1TQ3; X-ray; 1.89 A; A=302-402.
DR PDB; 2KA9; NMR; -; A=61-249.
DR PDB; 2MHO; NMR; -; A=60-155.
DR PDB; 2XKX; Other; 22.90 A; A/B=1-724.
DR PDB; 3GSL; X-ray; 2.05 A; A/B=61-249.
DR PDB; 3WP0; X-ray; 2.04 A; A=531-713.
DR PDB; 3WP1; X-ray; 2.80 A; B=531-713.
DR PDB; 5B64; X-ray; 2.70 A; A=531-713.
DR PDB; 5D13; X-ray; 2.15 A; A/B/C/D=302-402.
DR PDB; 5GNV; X-ray; 2.60 A; A=531-713.
DR PDB; 5HDY; X-ray; 1.80 A; A=302-402.
DR PDB; 5HEB; X-ray; 1.65 A; A=302-402.
DR PDB; 5HED; X-ray; 1.70 A; A=302-402.
DR PDB; 5HET; X-ray; 2.00 A; A=302-402.
DR PDB; 5HEY; X-ray; 1.50 A; A=302-402.
DR PDB; 5HF1; X-ray; 1.75 A; A=302-402.
DR PDB; 5HF4; X-ray; 1.75 A; A=302-402.
DR PDB; 5HFB; X-ray; 1.62 A; A=302-402.
DR PDB; 5HFC; X-ray; 1.85 A; A=302-402.
DR PDB; 5HFD; X-ray; 1.60 A; A=302-402.
DR PDB; 5HFE; X-ray; 1.80 A; A=302-402.
DR PDB; 5HFF; X-ray; 1.75 A; A=302-402.
DR PDB; 5MZ7; X-ray; 1.53 A; A/B/C/D=303-402.
DR PDB; 5W72; NMR; -; A=301-402.
DR PDB; 5YPO; X-ray; 2.29 A; A/B=531-713.
DR PDB; 5YPR; X-ray; 2.35 A; A=426-721.
DR PDB; 7CQF; X-ray; 1.80 A; A=309-422.
DR PDB; 7F7G; X-ray; 2.45 A; A/B=531-713.
DR PDB; 7F7I; X-ray; 2.60 A; A/B/C/D/E/F=531-713.
DR PDBsum; 1BE9; -.
DR PDBsum; 1BFE; -.
DR PDBsum; 1IU0; -.
DR PDBsum; 1IU2; -.
DR PDBsum; 1JXM; -.
DR PDBsum; 1JXO; -.
DR PDBsum; 1KJW; -.
DR PDBsum; 1QLC; -.
DR PDBsum; 1RGR; -.
DR PDBsum; 1TP3; -.
DR PDBsum; 1TP5; -.
DR PDBsum; 1TQ3; -.
DR PDBsum; 2KA9; -.
DR PDBsum; 2MHO; -.
DR PDBsum; 2XKX; -.
DR PDBsum; 3GSL; -.
DR PDBsum; 3WP0; -.
DR PDBsum; 3WP1; -.
DR PDBsum; 5B64; -.
DR PDBsum; 5D13; -.
DR PDBsum; 5GNV; -.
DR PDBsum; 5HDY; -.
DR PDBsum; 5HEB; -.
DR PDBsum; 5HED; -.
DR PDBsum; 5HET; -.
DR PDBsum; 5HEY; -.
DR PDBsum; 5HF1; -.
DR PDBsum; 5HF4; -.
DR PDBsum; 5HFB; -.
DR PDBsum; 5HFC; -.
DR PDBsum; 5HFD; -.
DR PDBsum; 5HFE; -.
DR PDBsum; 5HFF; -.
DR PDBsum; 5MZ7; -.
DR PDBsum; 5W72; -.
DR PDBsum; 5YPO; -.
DR PDBsum; 5YPR; -.
DR PDBsum; 7CQF; -.
DR PDBsum; 7F7G; -.
DR PDBsum; 7F7I; -.
DR AlphaFoldDB; P31016; -.
DR BMRB; P31016; -.
DR SMR; P31016; -.
DR BioGRID; 248135; 34.
DR CORUM; P31016; -.
DR DIP; DIP-29264N; -.
DR ELM; P31016; -.
DR IntAct; P31016; 353.
DR MINT; P31016; -.
DR STRING; 10116.ENSRNOP00000059045; -.
DR ChEMBL; CHEMBL3797015; -.
DR iPTMnet; P31016; -.
DR PhosphoSitePlus; P31016; -.
DR SwissPalm; P31016; -.
DR jPOST; P31016; -.
DR PaxDb; P31016; -.
DR PRIDE; P31016; -.
DR ABCD; P31016; 3 sequenced antibodies.
DR GeneID; 29495; -.
DR KEGG; rno:29495; -.
DR UCSC; RGD:68424; rat. [P31016-1]
DR CTD; 1742; -.
DR RGD; 68424; Dlg4.
DR VEuPathDB; HostDB:ENSRNOG00000018526; -.
DR eggNOG; KOG0708; Eukaryota.
DR HOGENOM; CLU_001715_4_2_1; -.
DR InParanoid; P31016; -.
DR OrthoDB; 836427at2759; -.
DR PhylomeDB; P31016; -.
DR Reactome; R-RNO-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-RNO-451308; Activation of Ca-permeable Kainate Receptor.
DR Reactome; R-RNO-5625900; RHO GTPases activate CIT.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-5682910; LGI-ADAM interactions.
DR Reactome; R-RNO-6794361; Neurexins and neuroligins.
DR Reactome; R-RNO-8849932; Synaptic adhesion-like molecules.
DR EvolutionaryTrace; P31016; -.
DR PRO; PR:P31016; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000018526; Expressed in frontal cortex and 20 other tissues.
DR ExpressionAtlas; P31016; baseline and differential.
DR Genevisible; P31016; RN.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:BHF-UCL.
DR GO; GO:0099031; C:anchored component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0030054; C:cell junction; ISS:BHF-UCL.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0044300; C:cerebellar mossy fiber; ISO:RGD.
DR GO; GO:0030863; C:cortical cytoskeleton; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0032839; C:dendrite cytoplasm; IDA:BHF-UCL.
DR GO; GO:0043197; C:dendritic spine; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0060076; C:excitatory synapse; IDA:BHF-UCL.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0031594; C:neuromuscular junction; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0044306; C:neuron projection terminus; ISS:BHF-UCL.
DR GO; GO:0044309; C:neuron spine; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0098794; C:postsynapse; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; ISO:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0097060; C:synaptic membrane; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; ISS:BHF-UCL.
DR GO; GO:0033130; F:acetylcholine receptor binding; IDA:RGD.
DR GO; GO:0031697; F:beta-1 adrenergic receptor binding; IPI:UniProtKB.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; IPI:ARUK-UCL.
DR GO; GO:0031748; F:D1 dopamine receptor binding; IPI:RGD.
DR GO; GO:0005109; F:frizzled binding; IPI:ARUK-UCL.
DR GO; GO:0035254; F:glutamate receptor binding; IPI:BHF-UCL.
DR GO; GO:0019865; F:immunoglobulin binding; IPI:UniProtKB.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0019894; F:kinesin binding; IPI:RGD.
DR GO; GO:0097109; F:neuroligin family protein binding; IPI:BHF-UCL.
DR GO; GO:0031812; F:P2Y1 nucleotide receptor binding; IPI:BHF-UCL.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0097110; F:scaffold protein binding; IPI:SynGO-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0098919; F:structural constituent of postsynaptic density; IDA:SynGO.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; IMP:BHF-UCL.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0035865; P:cellular response to potassium ion; ISO:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0060997; P:dendritic spine morphogenesis; IMP:BHF-UCL.
DR GO; GO:0097061; P:dendritic spine organization; IMP:UniProtKB.
DR GO; GO:0045184; P:establishment of protein localization; ISS:BHF-UCL.
DR GO; GO:0035641; P:locomotory exploration behavior; ISS:BHF-UCL.
DR GO; GO:0002091; P:negative regulation of receptor internalization; IDA:UniProtKB.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISS:BHF-UCL.
DR GO; GO:0045161; P:neuronal ion channel clustering; TAS:UniProtKB.
DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:RGD.
DR GO; GO:1904719; P:positive regulation of AMPA glutamate receptor clustering; IMP:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IDA:BHF-UCL.
DR GO; GO:0150012; P:positive regulation of neuron projection arborization; IGI:ARUK-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:ARUK-UCL.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; IDA:BHF-UCL.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; IMP:SynGO.
DR GO; GO:0035418; P:protein localization to synapse; IMP:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:BHF-UCL.
DR GO; GO:0043113; P:receptor clustering; IBA:GO_Central.
DR GO; GO:0097120; P:receptor localization to synapse; IMP:BHF-UCL.
DR GO; GO:2000821; P:regulation of grooming behavior; ISS:BHF-UCL.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISS:BHF-UCL.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:UniProtKB.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; IDA:BHF-UCL.
DR GO; GO:0035176; P:social behavior; ISS:BHF-UCL.
DR GO; GO:0016188; P:synaptic vesicle maturation; ISS:BHF-UCL.
DR GO; GO:0071625; P:vocalization behavior; ISS:BHF-UCL.
DR DisProt; DP01413; -.
DR Gene3D; 2.30.42.10; -; 3.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR016313; DLG1-like.
DR InterPro; IPR019590; DLG1_PEST_dom.
DR InterPro; IPR008145; GK/Ca_channel_bsu.
DR InterPro; IPR008144; Guanylate_kin-like_dom.
DR InterPro; IPR020590; Guanylate_kinase_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR019583; PDZ_assoc.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00625; Guanylate_kin; 1.
DR Pfam; PF10608; MAGUK_N_PEST; 1.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF10600; PDZ_assoc; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PIRSF; PIRSF001741; MAGUK_DLGH; 1.
DR SMART; SM00072; GuKc; 1.
DR SMART; SM01277; MAGUK_N_PEST; 1.
DR SMART; SM00228; PDZ; 3.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 3.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00856; GUANYLATE_KINASE_1; 1.
DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR PROSITE; PS50106; PDZ; 3.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Direct protein sequencing; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; SH3 domain; Synapse;
KW Ubl conjugation.
FT CHAIN 1..724
FT /note="Disks large homolog 4"
FT /id="PRO_0000094562"
FT DOMAIN 65..151
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 160..246
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 313..393
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 428..498
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 534..709
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 15..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 240
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 420
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 480
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 606
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 654
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 715
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:10629226,
FT ECO:0000269|PubMed:27307232"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:10629226,
FT ECO:0000269|PubMed:27307232"
FT MUTAGEN 3
FT /note="C->S: Loss of palmitoylation and targeting to
FT postsynaptic density."
FT /evidence="ECO:0000269|PubMed:10629226,
FT ECO:0000269|PubMed:27307232"
FT MUTAGEN 5
FT /note="C->S: Loss of palmitoylation and targeting to
FT postsynaptic density."
FT /evidence="ECO:0000269|PubMed:10629226,
FT ECO:0000269|PubMed:27307232"
FT MUTAGEN 13..24
FT /note="Missing: Greatly reduced ubiquitination."
FT /evidence="ECO:0000269|PubMed:14642282"
FT CONFLICT 61
FT /note="M -> L (in Ref. 2; CAA47103)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="S -> T (in Ref. 2; CAA47103)"
FT /evidence="ECO:0000305"
FT CONFLICT 177..182
FT /note="GVGNQH -> ALGTSI (in Ref. 2; CAA47103)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="A -> G (in Ref. 2; CAA47103)"
FT /evidence="ECO:0000305"
FT CONFLICT 254
FT /note="S -> T (in Ref. 2; CAA47103)"
FT /evidence="ECO:0000305"
FT CONFLICT 540..555
FT /note="LGPTKDRANDDLLSEF -> SLDPPKTVPTMIFSPSS (in Ref. 2;
FT CAA47103)"
FT /evidence="ECO:0000305"
FT CONFLICT 623..625
FT /note="GKH -> RDQ (in Ref. 4; AAB38270)"
FT /evidence="ECO:0000305"
FT STRAND 61..69
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:2KA9"
FT STRAND 74..80
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1IU0"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:1IU0"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:2KA9"
FT HELIX 104..108
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:3GSL"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:1IU2"
FT HELIX 130..138
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 142..151
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 156..166
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:3GSL"
FT HELIX 199..203
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:1QLC"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:3GSL"
FT STRAND 237..247
FT /evidence="ECO:0007829|PDB:3GSL"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:1TP5"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:5HEY"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:5MZ7"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:5HEY"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:5HEY"
FT STRAND 337..341
FT /evidence="ECO:0007829|PDB:5HEY"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:5HEY"
FT STRAND 357..362
FT /evidence="ECO:0007829|PDB:5HEY"
FT HELIX 372..380
FT /evidence="ECO:0007829|PDB:5HEY"
FT STRAND 384..392
FT /evidence="ECO:0007829|PDB:5HEY"
FT HELIX 394..398
FT /evidence="ECO:0007829|PDB:5HEY"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:1BE9"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:1BE9"
FT STRAND 431..437
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 441..445
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 449..451
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 459..464
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 467..475
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 486..489
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 491..499
FT /evidence="ECO:0007829|PDB:1KJW"
FT TURN 504..507
FT /evidence="ECO:0007829|PDB:1JXO"
FT STRAND 523..530
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 537..541
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 544..554
FT /evidence="ECO:0007829|PDB:1KJW"
FT TURN 556..558
FT /evidence="ECO:0007829|PDB:1KJW"
FT TURN 576..578
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 586..594
FT /evidence="ECO:0007829|PDB:1KJW"
FT TURN 595..597
FT /evidence="ECO:0007829|PDB:5GNV"
FT STRAND 598..604
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 607..612
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 613..621
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 625..628
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 634..640
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 646..650
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 655..661
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 663..665
FT /evidence="ECO:0007829|PDB:1JXM"
FT HELIX 667..684
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 685..687
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 689..692
FT /evidence="ECO:0007829|PDB:1KJW"
FT HELIX 697..711
FT /evidence="ECO:0007829|PDB:1KJW"
FT STRAND 714..719
FT /evidence="ECO:0007829|PDB:1KJW"
SQ SEQUENCE 724 AA; 80465 MW; 7922D4E8E0F9AD85 CRC64;
MDCLCIVTTK KYRYQDEDTP PLEHSPAHLP NQANSPPVIV NTDTLEAPGY ELQVNGTEGE
MEYEEITLER GNSGLGFSIA GGTDNPHIGD DPSIFITKII PGGAAAQDGR LRVNDSILFV
NEVDVREVTH SAAVEALKEA GSIVRLYVMR RKPPAEKVME IKLIKGPKGL GFSIAGGVGN
QHIPGDNSIY VTKIIEGGAA HKDGRLQIGD KILAVNSVGL EDVMHEDAVA ALKNTYDVVY
LKVAKPSNAY LSDSYAPPDI TTSYSQHLDN EISHSSYLGT DYPTAMTPTS PRRYSPVAKD
LLGEEDIPRE PRRIVIHRGS TGLGFNIVGG EDGEGIFISF ILAGGPADLS GELRKGDQIL
SVNGVDLRNA SHEQAAIALK NAGQTVTIIA QYKPEEYSRF EAKIHDLREQ LMNSSLGSGT
ASLRSNPKRG FYIRALFDYD KTKDCGFLSQ ALSFRFGDVL HVIDAGDEEW WQARRVHSDS
ETDDIGFIPS KRRVERREWS RLKAKDWGSS SGSQGREDSV LSYETVTQME VHYARPIIIL
GPTKDRANDD LLSEFPDKFG SCVPHTTRPK REYEIDGRDY HFVSSREKME KDIQAHKFIE
AGQYNSHLYG TSVQSVREVA EQGKHCILDV SANAVRRLQA AHLHPIAIFI RPRSLENVLE
INKRITEEQA RKAFDRATKL EQEFTECFSA IVEGDSFEEI YHKVKRVIED LSGPYIWVPA
RERL
