Reviewed, UniProtKB/Swiss-Prot Q62108 (DLG4_MOUSE)

Names and origin

Protein names

Recommended name:
    Disks large homolog 4
Alternative name(s):
    Postsynaptic density protein 95
      Short name=PSD-95
    Synapse-associated protein 90
      Short name=SAP90

Gene names

Name:	Dlg4
Synonyms:	Dlgh4, Psd95

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	724 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ACCN3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.
Subunit structure	Interacts through its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C, GRIN2D, ACCN3, certain splice forms of GRIN1, KCND2, CXADR, SYNGAP1, KCNA1, KCNA2, KCNA3, KCNA4 and ERBB4. Interacts through its first PDZ domain with GRIK2, KCNA4 and CRIPT. Interacts through its second PDZ domain with the PDZ domain of NOS1 or the C-terminus of CAPON. Interacts through its third PDZ domain with NLGN1 and CRIPT, and probably with NLGN2 and NLGN3. Interacts through its guanylate kinase-like domain with DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A, BEGAIN and KIF13B. Isoform 2 interacts through an L27 domain with HGS/HRS and the first L27 domain of CASK. Interacts with ANKS1B, LRFN1 and PRR7 By similarity. Interacts with ADR1B. May interact with HTR2A.
Subcellular location	MembraneBy similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic densityBy similarity. Cell junction › synapseBy similarity. Note= Membrane-associated. High levels in postsynaptic density of neurons in the forebrain. Also in presynaptic region of inhibitory synapses formed by cerebellar basket cells on axon hillocks of Purkinje cells By similarity.
Domain	The PDZ domain 3 mediates interaction with ADR1B. The L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to post-synaptic density By similarity.
Post-translational modification	Palmitoylation of isoform 1 is required for targeting to postsynaptic density By similarity.
Miscellaneous	Mice with a stop codon in the third PDZ domain have impaired spatial learning. NMDA-mediated synaptic plasticity is lost even though receptor levels and localization are unchanged. Long-term potentiation of synaptic transmission is enhanced due to minimal long-term depression.
Sequence similarities	Belongs to the MAGUK family. Contains 1 guanylate kinase-like domain. Contains 3 PDZ (DHR) domains. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Domain	Repeat SH3 domain
PTM	Lipoprotein Palmitate Phosphoprotein
Gene Ontology (GO)
Biological process	locomotory behavior Non-traceable author statement. Source: UniProtKB regulation of long-term neuronal synaptic plasticity Inferred from genetic interaction. Source: MGI response to cocaine Non-traceable author statement. Source: UniProtKB synaptic vesicle maturation Inferred from direct assay. Source: MGI synaptogenesis Non-traceable author statement. Source: UniProtKB
Cellular component	alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex Inferred from direct assay. Source: MGI cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Non-traceable author statement. Source: UniProtKB extrinsic to internal side of plasma membrane Inferred from direct assay. Source: MGI postsynaptic density Inferred from direct assay. Source: MGI postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW synaptosome Inferred from direct assay. Source: MGI
Molecular function	neurexin binding Non-traceable author statement. Source: UniProtKB protein C-terminus binding Non-traceable author statement. Source: UniProtKB receptor binding Non-traceable author statement. Source: UniProtKB structural molecule activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Grin2a	P35436	1	EBI-300895,EBI-400115
Grin2b	Q01097	1	EBI-300895,EBI-400125
Lrfn2	Q80TG9	2	EBI-300895,EBI-877092
Lrp1	Q91ZX7	1	EBI-300895,EBI-300955
Lrp8	Q924X6	1	EBI-300895,EBI-432319
ZDHHC17	Q8IUH5	1	EBI-300895,EBI-524753	From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q62108-1)

Also known as: PSD95-alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q62108-2)

Also known as: PSD95-beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MDCLCIVTTK → MSQRPRAPRSALWLLAPPLLRWAPPLLTVLHSDLFQALLDILDYYEACISESQ

Isoform 3 (identifier: Q62108-3)

The sequence of this isoform differs from the canonical sequence as follows:
     51-53: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 724	724	Disks large homolog 4		PRO_0000094561
Regions
	Domain	65 – 151	87	PDZ 1
	Domain	160 – 246	87	PDZ 2
	Domain	313 – 393	81	PDZ 3
	Domain	428 – 498	71	SH3
	Domain	534 – 709	176	Guanylate kinase-like
Amino acid modifications
	Modified residue	142	1	Phosphoserine
	Modified residue	240	1	Phosphotyrosine
	Modified residue	295	1	Phosphoserine
	Modified residue	397	1	Phosphotyrosine
	Modified residue	415	1	Phosphoserine
	Modified residue	418	1	Phosphoserine
	Modified residue	432	1	Phosphotyrosine
	Modified residue	580	1	Phosphotyrosine
	Modified residue	604	1	Phosphotyrosine
	Modified residue	701	1	Phosphotyrosine By similarity
	Modified residue	715	1	Phosphotyrosine
	Lipidation	3	1	S-palmitoyl cysteine By similarity
	Lipidation	5	1	S-palmitoyl cysteine By similarity
Natural variations
	Alternative sequence	1 – 10	10	MDCLCIVTTK → MSQRPRAPRSALWLLAPPLL RWAPPLLTVLHSDLFQALLD ILDYYEACISESQ in isoform 2.		VSP_014930
	Alternative sequence	51 – 53	3	Missing in isoform 3.		VSP_014931
Experimental info
	Sequence conflict	203	1	D → E in AAH14807. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PSD95-alpha) [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 7EFFC99E1FFF90BA	FASTA	724	80,472
	10 20 30 40 50 60 MDCLCIVTTK KYRYQDEDTP PLEHSPAHLP NQANSPPVIV NTDTLEAPGY ELQVNGTEGE 70 80 90 100 110 120 MEYEEITLER GNSGLGFSIA GGTDNPHIGD DPSIFITKII PGGAAAQDGR LRVNDSILFV 130 140 150 160 170 180 NEVDVREVTH SAAVEALKEA GSIVRLYVMR RKPPAEKIIE IKLIKGPKGL GFSIAGGVGN 190 200 210 220 230 240 QHIPGDNSIY VTKIIEGGAA HKDGRLQIGD KILAVNSVGL EDVMHEDAVA ALKNTYDVVY 250 260 270 280 290 300 LKVAKPSNAY LSDSYAPPDI TTSYSQHLDN EISHSSYLGT DYPTAMTPTS PRRYSPVAKD 310 320 330 340 350 360 LLGEEDIPRE PRRIVIHRGS TGLGFNIVGG EDGEGIFISF ILAGGPADLS GELRKGDQIL 370 380 390 400 410 420 SVNGVDLRNA SHEQAAIALK NAGQTVTIIA QYKPEEYSRF EAKIHDLREQ LMNSSLGSGT 430 440 450 460 470 480 ASLRSNPKRG FYIRALFDYD KTKDCGFLSQ ALSFHFGDVL HVIDASDEEW WQARRVHSDS 490 500 510 520 530 540 ETDDIGFIPS KRRVERREWS RLKAKDWGSS SGSQGREDSV LSYETVTQME VHYARPIIIL 550 560 570 580 590 600 GPTKDRANDD LLSEFPDKFG SCVPHTTRPK REYEIDGRDY HFVSSREKME KDIQAHKFIE 610 620 630 640 650 660 AGQYNSHLYG TSVQSVREVA EQGKHCILDV SANAVRRLQA AHLHPIAIFI RPRSLENVLE 670 680 690 700 710 720 INKRITEEQA RKAFDRATKL EQEFTECFSA IVEGDSFEEI YHKVKRVIED LSGPYIWVPA RERL
	Isoform 2 (PSD95-beta) [UniParc]. Checksum: 650F267DF8139740		767	85,423
	10 20 30 40 50 60 MSQRPRAPRS ALWLLAPPLL RWAPPLLTVL HSDLFQALLD ILDYYEACIS ESQKYRYQDE 70 80 90 100 110 120 DTPPLEHSPA HLPNQANSPP VIVNTDTLEA PGYELQVNGT EGEMEYEEIT LERGNSGLGF 130 140 150 160 170 180 SIAGGTDNPH IGDDPSIFIT KIIPGGAAAQ DGRLRVNDSI LFVNEVDVRE VTHSAAVEAL 190 200 210 220 230 240 KEAGSIVRLY VMRRKPPAEK IIEIKLIKGP KGLGFSIAGG VGNQHIPGDN SIYVTKIIEG 250 260 270 280 290 300 GAAHKDGRLQ IGDKILAVNS VGLEDVMHED AVAALKNTYD VVYLKVAKPS NAYLSDSYAP 310 320 330 340 350 360 PDITTSYSQH LDNEISHSSY LGTDYPTAMT PTSPRRYSPV AKDLLGEEDI PREPRRIVIH 370 380 390 400 410 420 RGSTGLGFNI VGGEDGEGIF ISFILAGGPA DLSGELRKGD QILSVNGVDL RNASHEQAAI 430 440 450 460 470 480 ALKNAGQTVT IIAQYKPEEY SRFEAKIHDL REQLMNSSLG SGTASLRSNP KRGFYIRALF 490 500 510 520 530 540 DYDKTKDCGF LSQALSFHFG DVLHVIDASD EEWWQARRVH SDSETDDIGF IPSKRRVERR 550 560 570 580 590 600 EWSRLKAKDW GSSSGSQGRE DSVLSYETVT QMEVHYARPI IILGPTKDRA NDDLLSEFPD 610 620 630 640 650 660 KFGSCVPHTT RPKREYEIDG RDYHFVSSRE KMEKDIQAHK FIEAGQYNSH LYGTSVQSVR 670 680 690 700 710 720 EVAEQGKHCI LDVSANAVRR LQAAHLHPIA IFIRPRSLEN VLEINKRITE EQARKAFDRA 730 740 750 760 TKLEQEFTEC FSAIVEGDSF EEIYHKVKRV IEDLSGPYIW VPARERL
	Isoform 3 [UniParc]. Checksum: 675C1EBD807CD37C		721	80,102
	10 20 30 40 50 60 MDCLCIVTTK KYRYQDEDTP PLEHSPAHLP NQANSPPVIV NTDTLEAPGY VNGTEGEMEY 70 80 90 100 110 120 EEITLERGNS GLGFSIAGGT DNPHIGDDPS IFITKIIPGG AAAQDGRLRV NDSILFVNEV 130 140 150 160 170 180 DVREVTHSAA VEALKEAGSI VRLYVMRRKP PAEKIIEIKL IKGPKGLGFS IAGGVGNQHI 190 200 210 220 230 240 PGDNSIYVTK IIEGGAAHKD GRLQIGDKIL AVNSVGLEDV MHEDAVAALK NTYDVVYLKV 250 260 270 280 290 300 AKPSNAYLSD SYAPPDITTS YSQHLDNEIS HSSYLGTDYP TAMTPTSPRR YSPVAKDLLG 310 320 330 340 350 360 EEDIPREPRR IVIHRGSTGL GFNIVGGEDG EGIFISFILA GGPADLSGEL RKGDQILSVN 370 380 390 400 410 420 GVDLRNASHE QAAIALKNAG QTVTIIAQYK PEEYSRFEAK IHDLREQLMN SSLGSGTASL 430 440 450 460 470 480 RSNPKRGFYI RALFDYDKTK DCGFLSQALS FHFGDVLHVI DASDEEWWQA RRVHSDSETD 490 500 510 520 530 540 DIGFIPSKRR VERREWSRLK AKDWGSSSGS QGREDSVLSY ETVTQMEVHY ARPIIILGPT 550 560 570 580 590 600 KDRANDDLLS EFPDKFGSCV PHTTRPKREY EIDGRDYHFV SSREKMEKDI QAHKFIEAGQ 610 620 630 640 650 660 YNSHLYGTSV QSVREVAEQG KHCILDVSAN AVRRLQAAHL HPIAIFIRPR SLENVLEINK 670 680 690 700 710 720 RITEEQARKA FDRATKLEQE FTECFSAIVE GDSFEEIYHK VKRVIEDLSG PYIWVPARER L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse homologue of rat PSD-95/SAP90A." Kohmura N., Yagi T. Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: DBA/2. Tissue: Brain.
[2]	The mouse genome sequencing consortium Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Strain: C57BL/6. Tissue: Retina.
[4]	"Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein." Migaud M., Charlesworth P., Dempster M., Webster L.C., Watabe A.M., Makhinson M., He Y., Ramsay M.F., Morris R.G.M., Morrison J.H., O'Dell T.J., Grant S.G.N. Nature 396:433-439(1998) [PubMed: 9853749] [Abstract] Cited for: FUNCTION, NULL MUTANT.
[5]	"The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins." Becamel C., Gavarini S., Chanrion B., Alonso G., Galeotti N., Dumuis A., Bockaert J., Marin P. J. Biol. Chem. 279:20257-20266(2004) [PubMed: 14988405] [Abstract] Cited for: INTERACTION WITH HTR2A.
[6]	"Interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) inhibits beta1-adrenergic receptor surface expression." He J., Bellini M., Xu J., Castleberry A.M., Hall R.A. J. Biol. Chem. 279:50190-50196(2004) [PubMed: 15358775] [Abstract] Cited for: INTERACTION WITH ADR1B, DOMAIN, FUNCTION.
[7]	"Proteomic analysis of in vivo phosphorylated synaptic proteins." Collins M.O., Yu L., Coba M.P., Husi H., Campuzano I., Blackstock W.P., Choudhary J.S., Grant S.G. J. Biol. Chem. 280:5972-5982(2005) [PubMed: 15572359] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415; SER-418 AND TYR-432, MASS SPECTROMETRY. Tissue: Brain.
[8]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed: 16452087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142; TYR-240 AND SER-295, MASS SPECTROMETRY. Tissue: Brain.
[9]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240; TYR-397; TYR-580; TYR-604 AND TYR-715, MASS SPECTROMETRY. Tissue: Brain.
[10]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-240; SER-415 AND SER-418, MASS SPECTROMETRY. Tissue: Brain cortex.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D50621 mRNA. Translation: BAA09297.1. AL596185 Genomic DNA. Translation: CAI35168.1. AL596185 Genomic DNA. Translation: CAI35169.1. AL596185 Genomic DNA. Translation: CAI35170.1. BC014807 mRNA. Translation: AAH14807.1.
RefSeq	NP_001103222.1. NP_031890.1.
UniGene	Mm.27256
3D structure databases
HSSP	HSSP built from PDB template 1KJW based on UniProtKB P31016.
SMR	Q62108. Positions 62-154, 155-249, 301-402, 430-724.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q62108.
PTM databases
PhosphoSite	Q62108.
Genome annotation databases
Ensembl	ENSMUSG00000020886. Mus musculus. [Contig view]
GeneID	13385.
KEGG	mmu:13385.
Organism-specific databases
MGI	MGI:1277959. Dlg4.
Phylogenomic databases
HOGENOM	Q62108.
HOVERGEN	Q62108.
Gene expression databases
ArrayExpress	Q62108.
CleanEx	MM_DLG4.
GermOnline	ENSMUSG00000020886. Mus musculus.
Family and domain databases
InterPro	IPR008144. Guanylate_kin. IPR008145. Guanylt/Ca. IPR016313. M-assoc_guanylate_kinase. IPR001478. PDZ. IPR001452. SH3. [Graphical view]
Pfam	PF00625. Guanylate_kin. 1 hit. PF00595. PDZ. 3 hits. PF00018. SH3_1. 1 hit. [Graphical view]
PIRSF	PIRSF001741. MAGUK_DLGH. 1 hit.
PRINTS	PR00452. SH3DOMAIN.
ProDom	PD000066. SH3. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00072. GuKc. 1 hit. SM00228. PDZ. 3 hits. SM00326. SH3. 1 hit. [Graphical view]
PROSITE	PS00856. GUANYLATE_KINASE_1. 1 hit. PS50052. GUANYLATE_KINASE_2. 1 hit. PS50106. PDZ. 3 hits. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	283740.
SOURCE	Search...

Entry information

Entry name

DLG4_MOUSE

Accession

Primary (citable) accession number: Q62108
Secondary accession number(s): Q5NCV5 , Q5NCV6, Q5NCV7, Q91WJ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	November 25, 2008
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)