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Protein

Disks large homolog 4

Gene

Dlg4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (Probable).2 Publications2 Publications

GO - Molecular functioni

GO - Biological processi

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 upon Ca2+ influx through NMDA receptor
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 Neurexins and neuroligins
R-MMU-8849932 Synaptic adhesion-like molecules

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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, 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

Palmitoylated. Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses. Palmitoylation may play a role in glutamate receptor GRIA1 synapse clustering. Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2. Undergoes rapid synaptic palmitoylation/depalmitoylation cycles during neuronal development which slow down in mature neurons.By similarity
Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62108
PeptideAtlasiQ62108
PRIDEiQ62108

PTM databases

iPTMnetiQ62108
PhosphoSitePlusiQ62108
SwissPalmiQ62108

Expressioni

Tissue specificityi

Highly expressed in CA1 stratum oriens and stratum radiatum hippocampal neurons.1 Publication

Gene expression databases

BgeeiENSMUSG00000020886 Expressed in 146 organ(s), highest expression level in cerebellum
CleanExiMM_DLG4
ExpressionAtlasiQ62108 baseline and differential
GenevisibleiQ62108 MM

Interactioni

Subunit structurei

Interacts through its PDZ domains with ANO2 and NETO1 (PubMed:19474308, PubMed:19243221). Interacts with KCNJ4 (By similarity). Interacts through its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C, GRIN2D (By similarity). Interacts with ERBB4 (By similarity). Interacts with KCNA1, KCNA2, KCNA3 and KCNA4 (By similarity). Interacts with SYNGAP1 (By similarity). Interacts with ASIC3 (By similarity). Interacts with CXADR (By similarity). Interacts with KCND2 (By similarity). Interacts with SEMA4C (PubMed:11134026). Interacts with LRRC4 and LRRC4B (PubMed:16980967). Interacts through its first PDZ domain with GRIK2 and CRIPT (By similarity). Interacts through its second PDZ domain with the PDZ domain of NOS1 or the C-terminus of CAPON (By similarity). Interacts through its third PDZ domain with NLGN1 and CRIPT, and probably with NLGN2 and NLGN3 (By similarity). Interacts through its guanylate kinase-like domain with DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A, BEGAIN, SIPA1L1 and KIF13B (By similarity). Isoform 2 interacts through an L27 domain with HGS/HRS and the first L27 domain of CASK (By similarity). Interacts with ADR1B (PubMed:15358775). Interacts with ANKS1B and PRR7 (By similarity). May interact with HTR2A (PubMed:14988405). Interacts with ADAM22, KLHL17 and LGI1 (PubMed:20089912) (By similarity). Interacts with FRMPD4 (via C-terminus) (By similarity). Interacts with LRFN1, LRFN2 and LRFN4 (PubMed:16828986). 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 (By similarity). Interacts (via N-terminus tandem pair of PDZ domains) with NOS1 (via N-terminal domain) (By similarity). Interacts with SHANK3 (PubMed:24153177). Interacts with KCNJ4 (PubMed:11997254). Interacts with GPR85 (By similarity). Interacts with CACNG2 and MPP2 (via the SH3-Guanylate kinase-like sub-module) (By similarity). Interacts with ADGRB1 (By similarity). Found in a complex with PRR7 and GRIN1 (By similarity). Interacts (via PDZ3 domain and to lesser degree via PDZ2 domain) with PRR7 (By similarity). Component of the postsynaptic hippocampal AMPA-type glutamate receptor (AMPAR) complex, at least composed of pore forming AMPAR subunits GRIA1, GRIA2 and GRIA3 and AMPAR auxiliary proteins SHISA6 and SHISA7. Interacts (via its first two PDZ domains) with SHISA6 and SHISA7 (via PDZ-binding motif); the interaction is direct (PubMed:26931375, PubMed:29199957).By similarity12 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199230, 199 interactors
CORUMiQ62108
DIPiDIP-29888N
IntActiQ62108, 425 interactors
MINTiQ62108
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
OMAiSHPNYLG
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
IPR036034 PDZ_sf
IPR036028 SH3-like_dom_sf
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

This entry has 3 described isoforms and 13 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3UZL5G3UZL5_MOUSE
Disks large homolog 4
Dlg4
668Annotation score:
B1AR31B1AR31_MOUSE
Disks large homolog 4
Dlg4
242Annotation score:
F6TPQ6F6TPQ6_MOUSE
Disks large homolog 4
Dlg4
130Annotation score:
E9Q3Z8E9Q3Z8_MOUSE
Disks large homolog 4
Dlg4
238Annotation score:
J3KMS4J3KMS4_MOUSE
Disks large homolog 4
Dlg4
51Annotation score:
J3QMR8J3QMR8_MOUSE
Disks large homolog 4
Dlg4
115Annotation score:
A0A338P6I6A0A338P6I6_MOUSE
Disks large homolog 4
Dlg4
764Annotation score:
A0A338P6E5A0A338P6E5_MOUSE
Disks large homolog 4
Dlg4
664Annotation score:
A0A338P7H1A0A338P7H1_MOUSE
Disks large homolog 4
Dlg4
198Annotation score:
A0A338P6L4A0A338P6L4_MOUSE
Disks large homolog 4
Dlg4
254Annotation score:
There are more potential isoformsShow all

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 No translation available.
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

EnsembliENSMUST00000108588; ENSMUSP00000104229; ENSMUSG00000020886 [Q62108-1]
ENSMUST00000108589; ENSMUSP00000104230; ENSMUSG00000020886 [Q62108-2]
ENSMUST00000231415; ENSMUSP00000156345; ENSMUSG00000020886 [Q62108-3]
GeneIDi13385
KEGGimmu:13385
UCSCiuc007jtp.2 mouse [Q62108-1]
uc007jtq.2 mouse [Q62108-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50621 mRNA Translation: BAA09297.1
AL596185 Genomic DNA No translation available.
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

3D structure databases

ProteinModelPortaliQ62108
SMRiQ62108
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199230, 199 interactors
CORUMiQ62108
DIPiDIP-29888N
IntActiQ62108, 425 interactors
MINTiQ62108
STRINGi10090.ENSMUSP00000018700

Chemistry databases

ChEMBLiCHEMBL1795134

PTM databases

iPTMnetiQ62108
PhosphoSitePlusiQ62108
SwissPalmiQ62108

Proteomic databases

PaxDbiQ62108
PeptideAtlasiQ62108
PRIDEiQ62108

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000108588; ENSMUSP00000104229; ENSMUSG00000020886 [Q62108-1]
ENSMUST00000108589; ENSMUSP00000104230; ENSMUSG00000020886 [Q62108-2]
ENSMUST00000231415; ENSMUSP00000156345; ENSMUSG00000020886 [Q62108-3]
GeneIDi13385
KEGGimmu:13385
UCSCiuc007jtp.2 mouse [Q62108-1]
uc007jtq.2 mouse [Q62108-3]

Organism-specific databases

CTDi1742
MGIiMGI:1277959 Dlg4

Phylogenomic databases

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

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 upon Ca2+ influx through NMDA receptor
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 Neurexins and neuroligins
R-MMU-8849932 Synaptic adhesion-like molecules

Miscellaneous databases

ChiTaRSiDlg4 mouse
PROiPR:Q62108
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020886 Expressed in 146 organ(s), highest expression level in cerebellum
CleanExiMM_DLG4
ExpressionAtlasiQ62108 baseline and differential
GenevisibleiQ62108 MM

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
IPR036034 PDZ_sf
IPR036028 SH3-like_dom_sf
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
ProtoNetiSearch...

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: November 7, 2018
This is version 196 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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