DLG4_MOUSE
ID DLG4_MOUSE Reviewed; 724 AA.
AC Q62108; Q5NCV5; Q5NCV6; Q5NCV7; Q91WJ1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Disks large homolog 4;
DE AltName: Full=Postsynaptic density protein 95 {ECO:0000305};
DE Short=PSD-95;
DE AltName: Full=Synapse-associated protein 90;
DE Short=SAP-90;
DE Short=SAP90;
GN Name=Dlg4 {ECO:0000312|MGI:MGI:1277959}; Synonyms=Dlgh4, Psd95;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=DBA/2J; TISSUE=Brain;
RA Kohmura N., Yagi T.;
RT "Mouse homologue of rat PSD-95/SAP90A.";
RL Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9853749; DOI=10.1038/24790;
RA Migaud M., Charlesworth P., Dempster M., Webster L.C., Watabe A.M.,
RA Makhinson M., He Y., Ramsay M.F., Morris R.G.M., Morrison J.H.,
RA O'Dell T.J., Grant S.G.N.;
RT "Enhanced long-term potentiation and impaired learning in mice with mutant
RT postsynaptic density-95 protein.";
RL Nature 396:433-439(1998).
RN [5]
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 [6]
RP INTERACTION WITH SEMA4F.
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 [7]
RP INTERACTION WITH KCNJ4.
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 [8]
RP INTERACTION WITH HTR2A.
RX PubMed=14988405; DOI=10.1074/jbc.m312106200;
RA Becamel C., Gavarini S., Chanrion B., Alonso G., Galeotti N., Dumuis A.,
RA Bockaert J., Marin P.;
RT "The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of
RT PDZ proteins.";
RL J. Biol. Chem. 279:20257-20266(2004).
RN [9]
RP INTERACTION WITH ADR1B, DOMAIN, AND FUNCTION.
RX PubMed=15358775; DOI=10.1074/jbc.m404876200;
RA He J., Bellini M., Xu J., Castleberry A.M., Hall R.A.;
RT "Interaction with cystic fibrosis transmembrane conductance regulator-
RT associated ligand (CAL) inhibits beta1-adrenergic receptor surface
RT expression.";
RL J. Biol. Chem. 279:50190-50196(2004).
RN [10]
RP INTERACTION WITH LRFN1; LRFN2 AND LRFN4.
RC STRAIN=Swiss Webster;
RX PubMed=16828986; DOI=10.1016/j.gene.2006.05.014;
RA Morimura N., Inoue T., Katayama K., Aruga J.;
RT "Comparative analysis of structure, expression and PSD95-binding capacity
RT of Lrfn, a novel family of neuronal transmembrane proteins.";
RL Gene 380:72-83(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [12]
RP INTERACTION WITH LRRC4B AND LRRC4.
RX PubMed=16980967; DOI=10.1038/nn1763;
RA Kim S., Burette A., Chung H.S., Kwon S.-K., Woo J., Lee H.W., Kim K.,
RA Kim H., Weinberg R.J., Kim E.;
RT "NGL family PSD-95-interacting adhesion molecules regulate excitatory
RT synapse formation.";
RL Nat. Neurosci. 9:1294-1301(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240; TYR-580 AND TYR-715, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [14]
RP INTERACTION WITH ANO2.
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=19474308; DOI=10.1523/jneurosci.5546-08.2009;
RA Stoehr H., Heisig J.B., Benz P.M., Schoeberl S., Milenkovic V.M.,
RA Strauss O., Aartsen W.M., Wijnholds J., Weber B.H.F., Schulz H.L.;
RT "TMEM16B, a novel protein with calcium-dependent chloride channel activity,
RT associates with a presynaptic protein complex in photoreceptor terminals.";
RL J. Neurosci. 29:6809-6818(2009).
RN [15]
RP INTERACTION WITH NETO1.
RX PubMed=19243221; DOI=10.1371/journal.pbio.1000041;
RA Ng D., Pitcher G.M., Szilard R.K., Sertie A., Kanisek M., Clapcote S.J.,
RA Lipina T., Kalia L.V., Joo D., McKerlie C., Cortez M., Roder J.C.,
RA Salter M.W., McInnes R.R.;
RT "Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for
RT synaptic plasticity and learning.";
RL PLoS Biol. 7:E41-E41(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73; TYR-240; SER-415;
RP SER-418; THR-420; SER-422; SER-425; SER-480 AND SER-606, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [17]
RP INTERACTION WITH ZDHHC5.
RX PubMed=20178993; DOI=10.1074/jbc.m109.079426;
RA Li Y., Hu J., Hoefer K., Wong A.M., Cooper J.D., Birnbaum S.G.,
RA Hammer R.E., Hofmann S.L.;
RT "DHHC5 interacts with PDZ domain 3 of post-synaptic density-95 (PSD-95)
RT protein and plays a role in learning and memory.";
RL J. Biol. Chem. 285:13022-13031(2010).
RN [18]
RP INTERACTION WITH ADAM22.
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 [19]
RP INTERACTION WITH SHANK3, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24153177; DOI=10.1038/nature12630;
RA Han K., Holder J.L. Jr., Schaaf C.P., Lu H., Chen H., Kang H., Tang J.,
RA Wu Z., Hao S., Cheung S.W., Yu P., Sun H., Breman A.M., Patel A., Lu H.C.,
RA Zoghbi H.Y.;
RT "SHANK3 overexpression causes manic-like behaviour with unique
RT pharmacogenetic properties.";
RL Nature 503:72-77(2013).
RN [20]
RP FUNCTION, INTERACTION WITH SHISA6, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=26931375; DOI=10.1038/ncomms10682;
RA Klaassen R.V., Stroeder J., Coussen F., Hafner A.S., Petersen J.D.,
RA Renancio C., Schmitz L.J., Normand E., Lodder J.C., Rotaru D.C.,
RA Rao-Ruiz P., Spijker S., Mansvelder H.D., Choquet D., Smit A.B.;
RT "Shisa6 traps AMPA receptors at postsynaptic sites and prevents their
RT desensitization during synaptic activity.";
RL Nat. Commun. 7:10682-10682(2016).
RN [21]
RP FUNCTION, INTERACTION WITH SHISA7, AND SUBCELLULAR LOCATION.
RX PubMed=29199957; DOI=10.7554/elife.24192;
RA Schmitz L.J.M., Klaassen R.V., Ruiperez-Alonso M., Zamri A.E., Stroeder J.,
RA Rao-Ruiz P., Lodder J.C., van der Loo R.J., Mansvelder H.D., Smit A.B.,
RA Spijker S.;
RT "The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic
RT function and contextual memory.";
RL Elife 6:0-0(2017).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=28334377; DOI=10.1167/iovs.16-20745;
RA Neuille M., Cao Y., Caplette R., Guerrero-Given D., Thomas C., Kamasawa N.,
RA Sahel J.A., Hamel C.P., Audo I., Picaud S., Martemyanov K.A., Zeitz C.;
RT "LRIT3 Differentially Affects Connectivity and Synaptic Transmission of
RT Cones to ON- and OFF-Bipolar Cells.";
RL Invest. Ophthalmol. Vis. Sci. 58:1768-1778(2017).
RN [23]
RP INTERACTION WITH C9ORF72; SMCR8 AND RAB39B, AND SUBCELLULAR LOCATION.
RX PubMed=31651360; DOI=10.1186/s40478-019-0812-5;
RA Xiao S., McKeever P.M., Lau A., Robertson J.;
RT "Synaptic localization of C9orf72 regulates post-synaptic glutamate
RT receptor 1 levels.";
RL Acta Neuropathol. Commun. 7:161-161(2019).
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:15358775, PubMed:9853749). Interacts with the cytoplasmic tail
CC of NMDA receptor subunits and shaker-type potassium channels. Required
CC for synaptic plasticity associated with NMDA receptor signaling.
CC Overexpression or depletion of DLG4 changes the ratio of excitatory to
CC inhibitory synapses in hippocampal neurons. May reduce the amplitude of
CC ASIC3 acid-evoked currents by retaining the channel intracellularly.
CC May regulate the intracellular trafficking of ADR1B. Also regulates
CC AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic
CC density keeping the channels in an activated state in the presence of
CC glutamate and preventing synaptic depression (Probable). Under basal
CC conditions, cooperates with FYN to stabilize palmitoyltransferase
CC ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of
CC ZDHHC5 and its subsequent inhibition of association with endocytic
CC proteins (By similarity). {ECO:0000250|UniProtKB:P78352,
CC ECO:0000269|PubMed:15358775, ECO:0000269|PubMed:9853749,
CC ECO:0000305|PubMed:26931375, ECO:0000305|PubMed:29199957}.
CC -!- SUBUNIT: Interacts through its PDZ domains with ANO2 and NETO1
CC (PubMed:19474308, PubMed:19243221). Interacts with KCNJ4 (By
CC similarity). Interacts through its first two PDZ domains with GRIN2A,
CC GRIN2B, GRIN2C, GRIN2D (By similarity). Interacts with ERBB4 (By
CC similarity). Interacts with KCNA1, KCNA2, KCNA3 and KCNA4 (By
CC similarity). Interacts with SYNGAP1 (By similarity). Interacts with
CC ASIC3 (By similarity). Interacts with CXADR (By similarity). Interacts
CC with KCND2 (By similarity). Interacts with SEMA4C (PubMed:11134026).
CC Interacts with LRRC4 and LRRC4B (PubMed:16980967). Interacts through
CC its first PDZ domain with GRIK2 and CRIPT (By similarity). Interacts
CC through its second PDZ domain with the PDZ domain of NOS1 or the C-
CC terminus of CAPON (By similarity). Interacts through its third PDZ
CC domain with NLGN1 and CRIPT, and probably with NLGN2 and NLGN3 (By
CC similarity). Interacts through its guanylate kinase-like domain with
CC DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A, BEGAIN, SIPA1L1 and KIF13B
CC (By similarity). Isoform 2 interacts through an L27 domain with HGS/HRS
CC and the first L27 domain of CASK (By similarity). Interacts with ADR1B
CC (PubMed:15358775). Interacts with ANKS1B and PRR7 (By similarity). May
CC interact with HTR2A (PubMed:14988405). Interacts with ADAM22, KLHL17
CC and LGI1 (PubMed:20089912) (By similarity). Interacts with FRMPD4 (via
CC C-terminus) (By similarity). Interacts with LRFN1, LRFN2 and LRFN4
CC (PubMed:16828986). Interacts (via N-terminal tandem pair of PDZ
CC domains) with GPER1 (via C-terminus tail motif); the interaction is
CC direct and induces the increase of GPER1 protein levels residing at the
CC plasma membrane surface in a estradiol-independent manner (By
CC similarity). Interacts (via N-terminus tandem pair of PDZ domains) with
CC NOS1 (via N-terminal domain) (By similarity). Interacts with SHANK3
CC (PubMed:24153177). Interacts with KCNJ4 (PubMed:11997254). Interacts
CC with GPR85 (By similarity). Interacts with CACNG2 and MPP2 (via the
CC SH3-Guanylate kinase-like sub-module) (By similarity). Interacts with
CC ADGRB1 (By similarity). Found in a complex with PRR7 and GRIN1 (By
CC similarity). Interacts (via PDZ3 domain and to lesser degree via PDZ2
CC domain) with PRR7 (By similarity). 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 (PubMed:26931375, PubMed:29199957). Interacts
CC (via PDZ domain 2) with SEMA4F (via PDZ-binding motif); this
CC interaction may promote translocation of DLG4/SAP90 to the membrane
CC (PubMed:11483650). Interacts with RPH3A and GRIN2A; this ternary
CC complex regulates NMDA receptor composition at postsynaptic membranes
CC (By similarity). Interacts with ABR and BCR (By similarity). Interacts
CC with DGKI (via PDZ-binding motif); controls the localization of DGKI to
CC the synapse (By similarity). Interacts with C9orf72, SMCR8 and RAB39B
CC (PubMed:31651360). Interacts with ZDHHC5 (PubMed:20178993).
CC {ECO:0000250|UniProtKB:P31016, ECO:0000250|UniProtKB:P78352,
CC ECO:0000269|PubMed:11134026, ECO:0000269|PubMed:11483650,
CC ECO:0000269|PubMed:11997254, ECO:0000269|PubMed:14988405,
CC ECO:0000269|PubMed:15358775, ECO:0000269|PubMed:16828986,
CC ECO:0000269|PubMed:16980967, ECO:0000269|PubMed:19243221,
CC ECO:0000269|PubMed:19474308, ECO:0000269|PubMed:20089912,
CC ECO:0000269|PubMed:20178993, ECO:0000269|PubMed:24153177,
CC ECO:0000269|PubMed:26931375, ECO:0000269|PubMed:29199957,
CC ECO:0000269|PubMed:31651360}.
CC -!- INTERACTION:
CC Q62108; Q8K4G5: Ablim1; NbExp=5; IntAct=EBI-300895, EBI-2307994;
CC Q62108; P12023: App; NbExp=4; IntAct=EBI-300895, EBI-78814;
CC Q62108; Q9WV31: Arc; NbExp=7; IntAct=EBI-300895, EBI-397779;
CC Q62108; Q8BKX1: Baiap2; NbExp=4; IntAct=EBI-300895, EBI-771498;
CC Q62108; P11798: Camk2a; NbExp=4; IntAct=EBI-300895, EBI-400384;
CC Q62108; P35347: Crhr1; NbExp=7; IntAct=EBI-300895, EBI-16879653;
CC Q62108; Q811D0: Dlg1; NbExp=4; IntAct=EBI-300895, EBI-514290;
CC Q62108; Q91XM9: Dlg2; NbExp=6; IntAct=EBI-300895, EBI-400138;
CC Q62108; P70175: Dlg3; NbExp=4; IntAct=EBI-300895, EBI-396969;
CC Q62108; Q61090: Fzd7; NbExp=4; IntAct=EBI-300895, EBI-8473104;
CC Q62108; Q9R111: Gda; NbExp=6; IntAct=EBI-300895, EBI-2308876;
CC Q62108; P35438: Grin1; NbExp=13; IntAct=EBI-300895, EBI-400084;
CC Q62108; P35436: Grin2a; NbExp=15; IntAct=EBI-300895, EBI-400115;
CC Q62108; Q01097: Grin2b; NbExp=19; IntAct=EBI-300895, EBI-400125;
CC Q62108; Q61423: Kcna4; NbExp=3; IntAct=EBI-300895, EBI-2309633;
CC Q62108; Q80TG9: Lrfn2; NbExp=3; IntAct=EBI-300895, EBI-877092;
CC Q62108; Q91ZX7: Lrp1; NbExp=4; IntAct=EBI-300895, EBI-300955;
CC Q62108; A2ARV4: Lrp2; NbExp=2; IntAct=EBI-300895, EBI-300875;
CC Q62108; Q924X6: Lrp8; NbExp=3; IntAct=EBI-300895, EBI-432319;
CC Q62108; P63085: Mapk1; NbExp=4; IntAct=EBI-300895, EBI-397697;
CC Q62108; P23804: Mdm2; NbExp=3; IntAct=EBI-300895, EBI-641788;
CC Q62108; Q8R4I7: Neto1; NbExp=7; IntAct=EBI-300895, EBI-2314926;
CC Q62108; Q810U4: Nrcam; NbExp=2; IntAct=EBI-300895, EBI-8321816;
CC Q62108; P46460: Nsf; NbExp=5; IntAct=EBI-300895, EBI-398006;
CC Q62108; P15209: Ntrk2; NbExp=4; IntAct=EBI-300895, EBI-309647;
CC Q62108; Q80TE2: Pcdh10; NbExp=4; IntAct=EBI-300895, EBI-6661550;
CC Q62108; Q14B62: ptchd1; NbExp=8; IntAct=EBI-300895, EBI-27105784;
CC Q62108; P63001: Rac1; NbExp=3; IntAct=EBI-300895, EBI-413646;
CC Q62108; Q8R550: Sh3kbp1; NbExp=3; IntAct=EBI-300895, EBI-642709;
CC Q62108; P30873: Sstr1; NbExp=3; IntAct=EBI-300895, EBI-7665262;
CC Q62108; P49660: Sstr4; NbExp=3; IntAct=EBI-300895, EBI-7665342;
CC Q62108; Q9WVI4: Gucy1a2; Xeno; NbExp=3; IntAct=EBI-300895, EBI-7665590;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P31016};
CC Lipid-anchor {ECO:0000250|UniProtKB:P31016}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P31016}. Postsynaptic density
CC {ECO:0000269|PubMed:26931375, ECO:0000269|PubMed:29199957,
CC ECO:0000269|PubMed:31651360}. Synapse {ECO:0000269|PubMed:24153177}.
CC Cytoplasm {ECO:0000250|UniProtKB:P31016}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P31016}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:P31016}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P31016}. Presynapse
CC {ECO:0000250|UniProtKB:P31016}. Note=High levels in postsynaptic
CC density of neurons in the forebrain. Also in presynaptic region of
CC inhibitory synapses formed by cerebellar basket cells on axon hillocks
CC of Purkinje cells. Suppression of neuronal activity induces synaptic
CC accumulation and clustering of DLG4. {ECO:0000250|UniProtKB:P31016}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=PSD95-alpha;
CC IsoId=Q62108-1; Sequence=Displayed;
CC Name=2; Synonyms=PSD95-beta;
CC IsoId=Q62108-2; Sequence=VSP_014930;
CC Name=3;
CC IsoId=Q62108-3; Sequence=VSP_014931;
CC -!- TISSUE SPECIFICITY: Highly expressed in CA1 stratum oriens and stratum
CC radiatum hippocampal neurons (PubMed:26931375). Expressed in the outer
CC plexiform layer of the retina of the eye (at protein level)
CC (PubMed:28334377). {ECO:0000269|PubMed:26931375,
CC ECO:0000269|PubMed:28334377}.
CC -!- DOMAIN: The PDZ domain 3 mediates interaction with ADR1B.
CC {ECO:0000269|PubMed:15358775}.
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. Palmitoylation is required for targeting to
CC postsynaptic density, plasma membrane and synapses. Palmitoylation by
CC ZDHHC2 occurs when the synaptic activity decreases and induces DLG4
CC synaptic clustering. Palmitoylation by ZDHHC15 regulates trafficking to
CC the postsynaptic density and function in synaptogenesis. Palmitoylation
CC may play a role in glutamate receptor GRIA1 synapse clustering.
CC Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by
CC ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2. Undergoes rapid synaptic
CC palmitoylation/depalmitoylation cycles during neuronal development
CC which slow down in mature neurons. {ECO:0000250|UniProtKB:P31016}.
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:0000250|UniProtKB:P31016}.
CC -!- DISRUPTION PHENOTYPE: Mice with a stop codon in the third PDZ domain
CC have impaired spatial learning. NMDA-mediated synaptic plasticity is
CC lost even though receptor levels and localization are unchanged. Long-
CC term potentiation of synaptic transmission is enhanced due to minimal
CC long-term depression. {ECO:0000269|PubMed:9853749}.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
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DR EMBL; D50621; BAA09297.1; -; mRNA.
DR EMBL; AL596185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014807; AAH14807.1; -; mRNA.
DR CCDS; CCDS36202.1; -. [Q62108-1]
DR CCDS; CCDS48829.1; -. [Q62108-3]
DR RefSeq; NP_001103222.1; NM_001109752.1. [Q62108-3]
DR RefSeq; NP_031890.1; NM_007864.3. [Q62108-1]
DR AlphaFoldDB; Q62108; -.
DR BMRB; Q62108; -.
DR SMR; Q62108; -.
DR BioGRID; 199230; 223.
DR CORUM; Q62108; -.
DR DIP; DIP-29888N; -.
DR IntAct; Q62108; 429.
DR MINT; Q62108; -.
DR STRING; 10090.ENSMUSP00000018700; -.
DR ChEMBL; CHEMBL1795134; -.
DR iPTMnet; Q62108; -.
DR PhosphoSitePlus; Q62108; -.
DR SwissPalm; Q62108; -.
DR EPD; Q62108; -.
DR jPOST; Q62108; -.
DR MaxQB; Q62108; -.
DR PaxDb; Q62108; -.
DR PeptideAtlas; Q62108; -.
DR PRIDE; Q62108; -.
DR ProteomicsDB; 279421; -. [Q62108-1]
DR ProteomicsDB; 279422; -. [Q62108-2]
DR ProteomicsDB; 279423; -. [Q62108-3]
DR ABCD; Q62108; 3 sequenced antibodies.
DR Antibodypedia; 1930; 866 antibodies from 50 providers.
DR DNASU; 13385; -.
DR Ensembl; ENSMUST00000108588; ENSMUSP00000104229; ENSMUSG00000020886. [Q62108-1]
DR Ensembl; ENSMUST00000108589; ENSMUSP00000104230; ENSMUSG00000020886. [Q62108-2]
DR Ensembl; ENSMUST00000231415; ENSMUSP00000156345; ENSMUSG00000020886. [Q62108-3]
DR GeneID; 13385; -.
DR KEGG; mmu:13385; -.
DR UCSC; uc007jtp.2; mouse. [Q62108-1]
DR UCSC; uc007jtq.2; mouse. [Q62108-3]
DR CTD; 1742; -.
DR MGI; MGI:1277959; Dlg4.
DR VEuPathDB; HostDB:ENSMUSG00000020886; -.
DR eggNOG; KOG0708; Eukaryota.
DR GeneTree; ENSGT00940000157956; -.
DR HOGENOM; CLU_001715_4_2_1; -.
DR InParanoid; Q62108; -.
DR OMA; SISESQX; -.
DR OrthoDB; 807583at2759; -.
DR PhylomeDB; Q62108; -.
DR TreeFam; TF323171; -.
DR Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-MMU-451308; Activation of Ca-permeable Kainate Receptor.
DR Reactome; R-MMU-5625900; RHO GTPases activate CIT.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-5682910; LGI-ADAM interactions.
DR Reactome; R-MMU-6794361; Neurexins and neuroligins.
DR Reactome; R-MMU-8849932; Synaptic adhesion-like molecules.
DR BioGRID-ORCS; 13385; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Dlg4; mouse.
DR PRO; PR:Q62108; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q62108; protein.
DR Bgee; ENSMUSG00000020886; Expressed in retinal neural layer and 173 other tissues.
DR ExpressionAtlas; Q62108; baseline and differential.
DR Genevisible; Q62108; MM.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IDA:MGI.
DR GO; GO:0099031; C:anchored component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0030054; C:cell junction; IDA:MGI.
DR GO; GO:0071944; C:cell periphery; IDA:MGI.
DR GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0044300; C:cerebellar mossy fiber; IDA:MGI.
DR GO; GO:0030863; C:cortical cytoskeleton; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0032839; C:dendrite cytoplasm; ISS:BHF-UCL.
DR GO; GO:0043197; C:dendritic spine; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0060076; C:excitatory synapse; IDA:BHF-UCL.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0044309; C:neuron spine; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0098794; C:postsynapse; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0097060; C:synaptic membrane; IDA:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IDA:MGI.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IEA:Ensembl.
DR GO; GO:0033130; F:acetylcholine receptor binding; ISS:BHF-UCL.
DR GO; GO:0031697; F:beta-1 adrenergic receptor binding; ISS:BHF-UCL.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; ISO:MGI.
DR GO; GO:0031748; F:D1 dopamine receptor binding; ISS:BHF-UCL.
DR GO; GO:0005109; F:frizzled binding; ISO:MGI.
DR GO; GO:0035254; F:glutamate receptor binding; ISO:MGI.
DR GO; GO:0019865; F:immunoglobulin binding; ISO:MGI.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:BHF-UCL.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0019894; F:kinesin binding; ISO:MGI.
DR GO; GO:0042043; F:neurexin family protein binding; NAS:UniProtKB.
DR GO; GO:0097109; F:neuroligin family protein binding; ISS:BHF-UCL.
DR GO; GO:0031812; F:P2Y1 nucleotide receptor binding; ISS:BHF-UCL.
DR GO; GO:0030165; F:PDZ domain binding; ISS:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; ISS:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISS:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:BHF-UCL.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0098919; F:structural constituent of postsynaptic density; ISO:MGI.
DR GO; GO:0005198; F:structural molecule activity; NAS:UniProtKB.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; ISS:BHF-UCL.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0035865; P:cellular response to potassium ion; IDA:ARUK-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0060997; P:dendritic spine morphogenesis; IDA:BHF-UCL.
DR GO; GO:0097061; P:dendritic spine organization; ISO:MGI.
DR GO; GO:0045184; P:establishment of protein localization; ISS:BHF-UCL.
DR GO; GO:0007626; P:locomotory behavior; NAS:UniProtKB.
DR GO; GO:0035641; P:locomotory exploration behavior; IMP:BHF-UCL.
DR GO; GO:0002091; P:negative regulation of receptor internalization; ISS:BHF-UCL.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IMP:BHF-UCL.
DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:1904719; P:positive regulation of AMPA glutamate receptor clustering; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:BHF-UCL.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:0150012; P:positive regulation of neuron projection arborization; ISO:MGI.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISS:BHF-UCL.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; ISO:MGI.
DR GO; GO:0035418; P:protein localization to synapse; IDA:MGI.
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; ISS:BHF-UCL.
DR GO; GO:2000821; P:regulation of grooming behavior; IMP:BHF-UCL.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IGI:MGI.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISO:MGI.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:BHF-UCL.
DR GO; GO:0042220; P:response to cocaine; NAS:UniProtKB.
DR GO; GO:0035176; P:social behavior; IMP:BHF-UCL.
DR GO; GO:0016188; P:synaptic vesicle maturation; IDA:MGI.
DR GO; GO:0071625; P:vocalization behavior; IMP:BHF-UCL.
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 Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Reference proteome;
KW Repeat; SH3 domain; Synapse; Ubl conjugation.
FT CHAIN 1..724
FT /note="Disks large homolog 4"
FT /id="PRO_0000094561"
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:0007744|PubMed:21183079"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087"
FT MOD_RES 240
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 420
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT MOD_RES 480
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 606
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 654
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT MOD_RES 715
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT VAR_SEQ 1..10
FT /note="MDCLCIVTTK -> MSQRPRAPRSALWLLAPPLLRWAPPLLTVLHSDLFQAL
FT LDILDYYEACISESQ (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_014930"
FT VAR_SEQ 51..53
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014931"
FT CONFLICT 203
FT /note="D -> E (in Ref. 3; AAH14807)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 724 AA; 80472 MW; 7EFFC99E1FFF90BA CRC64;
MDCLCIVTTK KYRYQDEDTP PLEHSPAHLP NQANSPPVIV NTDTLEAPGY ELQVNGTEGE
MEYEEITLER GNSGLGFSIA GGTDNPHIGD DPSIFITKII PGGAAAQDGR LRVNDSILFV
NEVDVREVTH SAAVEALKEA GSIVRLYVMR RKPPAEKIIE 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 ALSFHFGDVL HVIDASDEEW 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
