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Protein

Disks large homolog 4

Gene

Dlg4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.2 Publications

GO - Molecular functioni

GO - Biological processi

  • AMPA glutamate receptor clustering Source: BHF-UCL
  • dendritic spine morphogenesis Source: BHF-UCL
  • establishment of protein localization Source: BHF-UCL
  • establishment or maintenance of epithelial cell apical/basal polarity Source: GO_Central
  • locomotory behavior Source: UniProtKB
  • locomotory exploration behavior Source: BHF-UCL
  • negative regulation of receptor internalization Source: BHF-UCL
  • neuromuscular process controlling balance Source: BHF-UCL
  • positive regulation of cytosolic calcium ion concentration Source: BHF-UCL
  • positive regulation of excitatory postsynaptic potential Source: BHF-UCL
  • positive regulation of synaptic transmission Source: BHF-UCL
  • protein complex assembly Source: BHF-UCL
  • protein localization to synapse Source: MGI
  • receptor clustering Source: GO_Central
  • receptor localization to synapse Source: BHF-UCL
  • regulation of grooming behavior Source: BHF-UCL
  • regulation of long-term neuronal synaptic plasticity Source: MGI
  • regulation of neuronal synaptic plasticity Source: UniProtKB
  • regulation of NMDA receptor activity Source: BHF-UCL
  • response to cocaine Source: UniProtKB
  • social behavior Source: BHF-UCL
  • synaptic vesicle maturation Source: MGI
  • vocalization behavior Source: BHF-UCL

Enzyme and pathway databases

ReactomeiR-MMU-399719. Trafficking of AMPA receptors.
R-MMU-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-MMU-442729. CREB phosphorylation through the activation of CaMKII.
R-MMU-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-MMU-447038. NrCAM interactions.
R-MMU-451308. Activation of Ca-permeable Kainate Receptor.
R-MMU-5625900. RHO GTPases activate CIT.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-5682910. LGI-ADAM interactions.
R-MMU-6794361. Interactions of neurexins and neuroligins at synapses.
R-MMU-8849932. SALM protein interactions at the synapses.

Names & Taxonomyi

Protein namesi
Recommended name:
Disks large homolog 4
Alternative name(s):
Postsynaptic density protein 95
Short name:
PSD-95
Synapse-associated protein 90
Short name:
SAP-90
Short name:
SAP90
Gene namesi
Name:Dlg4
Synonyms:Dlgh4, Psd95
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1277959. Dlg4.

Subcellular locationi

GO - Cellular componenti

  • AMPA glutamate receptor complex Source: MGI
  • basolateral plasma membrane Source: GO_Central
  • cell junction Source: MGI
  • cell periphery Source: MGI
  • cerebellar mossy fiber Source: MGI
  • cortical cytoskeleton Source: MGI
  • cytoplasm Source: MGI
  • dendrite Source: MGI
  • dendrite cytoplasm Source: BHF-UCL
  • dendritic spine Source: ParkinsonsUK-UCL
  • endoplasmic reticulum Source: MGI
  • excitatory synapse Source: BHF-UCL
  • extrinsic component of cytoplasmic side of plasma membrane Source: MGI
  • juxtaparanode region of axon Source: MGI
  • membrane Source: MGI
  • neuron projection terminus Source: MGI
  • neuron spine Source: BHF-UCL
  • plasma membrane Source: MGI
  • postsynaptic density Source: ParkinsonsUK-UCL
  • postsynaptic density membrane Source: SynGO
  • postsynaptic membrane Source: MGI
  • synapse Source: MGI
  • synaptic membrane Source: MGI
  • synaptic vesicle Source: MGI

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Chemistry databases

ChEMBLiCHEMBL1795134.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000945611 – 724Disks large homolog 4Add BLAST724

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi3S-palmitoyl cysteineBy similarity1
Lipidationi5S-palmitoyl cysteineBy similarity1
Modified residuei73PhosphoserineCombined sources1
Modified residuei142PhosphoserineCombined sources1
Modified residuei240PhosphotyrosineCombined sources1
Modified residuei295PhosphoserineBy similarity1
Modified residuei415PhosphoserineCombined sources1
Modified residuei418PhosphoserineCombined sources1
Modified residuei420PhosphothreonineCombined sources1
Modified residuei422PhosphoserineCombined sources1
Modified residuei425PhosphoserineCombined sources1
Modified residuei449PhosphoserineBy similarity1
Modified residuei480PhosphoserineCombined sources1
Modified residuei580PhosphotyrosineCombined sources1
Modified residuei606PhosphoserineCombined sources1
Modified residuei654PhosphoserineBy similarity1
Modified residuei715PhosphotyrosineCombined sources1

Post-translational modificationi

Palmitoylation of isoform 1 is required for targeting to postsynaptic density.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ62108.
PeptideAtlasiQ62108.
PRIDEiQ62108.

PTM databases

iPTMnetiQ62108.
PhosphoSitePlusiQ62108.
SwissPalmiQ62108.

Expressioni

Gene expression databases

BgeeiENSMUSG00000020886.
CleanExiMM_DLG4.
ExpressionAtlasiQ62108. baseline and differential.
GenevisibleiQ62108. MM.

Interactioni

Subunit structurei

Interacts through its PDZ domains with ANO2 and NETO1. Interacts through its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C, GRIN2D, ASIC3, certain splice forms of GRIN1, KCND2, CXADR, SYNGAP1, KCNA1, KCNA2, KCNA3, KCNA4, ERBB4, LRRC4; LRRC4B and SEMA4C. 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, SIPA1L1 and KIF13B. Isoform 2 interacts through an L27 domain with HGS/HRS and the first L27 domain of CASK. Interacts with ADR1B, ANKS1B and PRR7. May interact with HTR2A. Interacts with ADAM22, KLHL17 and LGI1. Interacts with FRMPD4 (via C-terminus). Interacts with LRFN1, LRFN2 and LRFN4, but not with LRFN3 nor LRFN5. Interacts (via N-terminal tandem pair of PDZ domains) with GPER1 (via C-terminus tail motif); the interaction is direct and induces the increase of GPER1 protein levels residing at the plasma membrane surface in a estradiol-independent manner. Interacts (via N-terminus tandem pair of PDZ domains) with NOS1 (via N-terminal domain). Interacts with SHANK3. Interacts with KCNJ4. Interacts with GPR85 (By similarity). Interacts with CACNG2 and MPP2 (via the SH3-Guanylate kinase-like sub-module) (By similarity).By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199230. 146 interactors.
DIPiDIP-29888N.
IntActiQ62108. 341 interactors.
MINTiMINT-136080.
STRINGi10090.ENSMUSP00000018700.

Structurei

3D structure databases

ProteinModelPortaliQ62108.
SMRiQ62108.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 151PDZ 1PROSITE-ProRule annotationAdd BLAST87
Domaini160 – 246PDZ 2PROSITE-ProRule annotationAdd BLAST87
Domaini313 – 393PDZ 3PROSITE-ProRule annotationAdd BLAST81
Domaini428 – 498SH3PROSITE-ProRule annotationAdd BLAST71
Domaini534 – 709Guanylate kinase-likePROSITE-ProRule annotationAdd BLAST176

Domaini

The PDZ domain 3 mediates interaction with ADR1B.1 Publication
The L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to postsynaptic density.By similarity

Sequence similaritiesi

Belongs to the MAGUK family.Curated

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG0708. Eukaryota.
COG0194. LUCA.
GeneTreeiENSGT00760000118866.
HOGENOMiHOG000232102.
HOVERGENiHBG107814.
InParanoidiQ62108.
KOiK11828.
OMAiQVEVHYA.
OrthoDBiEOG091G0BB1.
PhylomeDBiQ62108.
TreeFamiTF323171.

Family and domain databases

InterProiView protein in InterPro
IPR016313. DLG1-like.
IPR019590. DLG1_PEST_dom.
IPR008145. GK/Ca_channel_bsu.
IPR008144. Guanylate_kin-like_dom.
IPR020590. Guanylate_kinase_CS.
IPR027417. P-loop_NTPase.
IPR001478. PDZ.
IPR019583. PDZ_assoc.
IPR001452. SH3_domain.
PfamiView protein in Pfam
PF00625. Guanylate_kin. 1 hit.
PF10608. MAGUK_N_PEST. 1 hit.
PF00595. PDZ. 3 hits.
PF10600. PDZ_assoc. 1 hit.
PF00018. SH3_1. 1 hit.
PIRSFiPIRSF001741. MAGUK_DLGH. 1 hit.
SMARTiView protein in SMART
SM00072. GuKc. 1 hit.
SM01277. MAGUK_N_PEST. 1 hit.
SM00228. PDZ. 3 hits.
SM00326. SH3. 1 hit.
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF50156. SSF50156. 3 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS00856. GUANYLATE_KINASE_1. 1 hit.
PS50052. GUANYLATE_KINASE_2. 1 hit.
PS50106. PDZ. 3 hits.
PS50002. SH3. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q62108-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MDCLCIVTTK KYRYQDEDTP PLEHSPAHLP NQANSPPVIV NTDTLEAPGY
60 70 80 90 100
ELQVNGTEGE MEYEEITLER GNSGLGFSIA GGTDNPHIGD DPSIFITKII
110 120 130 140 150
PGGAAAQDGR LRVNDSILFV NEVDVREVTH SAAVEALKEA GSIVRLYVMR
160 170 180 190 200
RKPPAEKIIE IKLIKGPKGL GFSIAGGVGN QHIPGDNSIY VTKIIEGGAA
210 220 230 240 250
HKDGRLQIGD KILAVNSVGL EDVMHEDAVA ALKNTYDVVY LKVAKPSNAY
260 270 280 290 300
LSDSYAPPDI TTSYSQHLDN EISHSSYLGT DYPTAMTPTS PRRYSPVAKD
310 320 330 340 350
LLGEEDIPRE PRRIVIHRGS TGLGFNIVGG EDGEGIFISF ILAGGPADLS
360 370 380 390 400
GELRKGDQIL SVNGVDLRNA SHEQAAIALK NAGQTVTIIA QYKPEEYSRF
410 420 430 440 450
EAKIHDLREQ LMNSSLGSGT ASLRSNPKRG FYIRALFDYD KTKDCGFLSQ
460 470 480 490 500
ALSFHFGDVL HVIDASDEEW WQARRVHSDS ETDDIGFIPS KRRVERREWS
510 520 530 540 550
RLKAKDWGSS SGSQGREDSV LSYETVTQME VHYARPIIIL GPTKDRANDD
560 570 580 590 600
LLSEFPDKFG SCVPHTTRPK REYEIDGRDY HFVSSREKME KDIQAHKFIE
610 620 630 640 650
AGQYNSHLYG TSVQSVREVA EQGKHCILDV SANAVRRLQA AHLHPIAIFI
660 670 680 690 700
RPRSLENVLE INKRITEEQA RKAFDRATKL EQEFTECFSA IVEGDSFEEI
710 720
YHKVKRVIED LSGPYIWVPA RERL
Length:724
Mass (Da):80,472
Last modified:November 1, 1997 - v1
Checksum:i7EFFC99E1FFF90BA
GO
Isoform 2 (identifier: Q62108-2) [UniParc]FASTAAdd to basket
Also known as: PSD95-beta

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

Show »
Length:767
Mass (Da):85,423
Checksum:i650F267DF8139740
GO
Isoform 3 (identifier: Q62108-3) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:721
Mass (Da):80,102
Checksum:i675C1EBD807CD37C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti203D → E in AAH14807 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0149301 – 10MDCLCIVTTK → MSQRPRAPRSALWLLAPPLL RWAPPLLTVLHSDLFQALLD ILDYYEACISESQ in isoform 2. Curated10
Alternative sequenceiVSP_01493151 – 53Missing in isoform 3. 1 Publication3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS36202.1. [Q62108-1]
CCDS48829.1. [Q62108-3]
RefSeqiNP_001103222.1. NM_001109752.1. [Q62108-3]
NP_031890.1. NM_007864.3. [Q62108-1]
UniGeneiMm.27256.

Genome annotation databases

EnsembliENSMUST00000018700; ENSMUSP00000018700; ENSMUSG00000020886. [Q62108-1]
ENSMUST00000108588; ENSMUSP00000104229; ENSMUSG00000020886. [Q62108-3]
ENSMUST00000108589; ENSMUSP00000104230; ENSMUSG00000020886. [Q62108-2]
GeneIDi13385.
KEGGimmu:13385.
UCSCiuc007jtp.2. mouse. [Q62108-1]
uc007jtq.2. mouse. [Q62108-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDLG4_MOUSE
AccessioniPrimary (citable) accession number: Q62108
Secondary accession number(s): Q5NCV5
, Q5NCV6, Q5NCV7, Q91WJ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: August 30, 2017
This is version 182 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families