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Protein

Disks large homolog 4

Gene

Dlg4

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-RNO-399719 Trafficking of AMPA receptors
R-RNO-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-RNO-442729 CREB phosphorylation through the activation of CaMKII
R-RNO-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-RNO-451308 Activation of Ca-permeable Kainate Receptor
R-RNO-5625900 RHO GTPases activate CIT
R-RNO-5673001 RAF/MAP kinase cascade
R-RNO-5682910 LGI-ADAM interactions
R-RNO-6794361 Neurexins and neuroligins
R-RNO-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, Psd951 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi68424 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3C → S: Loss of palmitoylation and targeting to postsynaptic density. 2 Publications1
Mutagenesisi5C → S: Loss of palmitoylation and targeting to postsynaptic density. 2 Publications1
Mutagenesisi13 – 24Missing : Greatly reduced ubiquitination. 1 PublicationAdd BLAST12

Chemistry databases

ChEMBLiCHEMBL3797015

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000945621 – 724Disks large homolog 4Add BLAST724

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi3S-palmitoyl cysteine2 Publications1
Lipidationi5S-palmitoyl cysteine2 Publications1
Modified residuei73PhosphoserineBy similarity1
Modified residuei142PhosphoserineBy similarity1
Modified residuei240PhosphotyrosineCombined sources1
Modified residuei295PhosphoserineCombined sources1
Modified residuei415PhosphoserineBy similarity1
Modified residuei418PhosphoserineCombined sources1
Modified residuei420PhosphothreonineCombined sources1
Modified residuei422PhosphoserineCombined sources1
Modified residuei425PhosphoserineBy similarity1
Modified residuei449PhosphoserineCombined sources1
Modified residuei480PhosphoserineBy similarity1
Modified residuei580PhosphotyrosineBy similarity1
Modified residuei606PhosphoserineBy similarity1
Modified residuei654PhosphoserineCombined sources1
Modified residuei715PhosphotyrosineBy similarity1

Post-translational modificationi

Palmitoylated (PubMed:10629226, PubMed:27307232). Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses (PubMed:10629226, PubMed:27307232). Palmitoylation may play a role in glutamate receptor GRIA1 synapse clustering (PubMed:27307232). Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2 (PubMed:27307232). Undergoes rapid synaptic palmitoylation/depalmitoylation cycle during neuronal development which slows down in mature neurons (PubMed:27307232).2 Publications
Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP31016
PRIDEiP31016

PTM databases

iPTMnetiP31016
PhosphoSitePlusiP31016
SwissPalmiP31016

Expressioni

Tissue specificityi

Expressed in brain (at protein level) (PubMed:12151521, PubMed:27307232). Detected in juxtaparanodal zones in the central nervous system and at nerve terminal plexuses of basket cells in the cerebellum (PubMed:20089912). Expressed in cerebrum (PubMed:27307232). Expressed in hippocampal neurons (at protein level) (PubMed:11502259, PubMed:12151521, PubMed:27307232, PubMed:27756895). Isoform 1 and isoform 2: highly expressed in cerebellum, cortex, hippocampus, and corpus striatum (PubMed:12151521).5 Publications

Gene expression databases

BgeeiENSRNOG00000018526 Expressed in 10 organ(s), highest expression level in brain
ExpressionAtlasiP31016 baseline and differential
GenevisibleiP31016 RN

Interactioni

Subunit structurei

Interacts through its PDZ domains with ANO2 and NETO1 (By similarity). Interacts with KCNJ4 (PubMed:11997254). Interacts through its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C and GRIN2D (PubMed:7569905). Interacts with ERBB4 (By similarity). Interacts with KCNA1, KCNA2, KCNA3 and KCNA4 (By similarity). Interacts with LRRC4 and LRRC4B (By similarity). Interacts with SYNGAP1 (PubMed:9581761). Interacts with ASIC3 (PubMed:15317815). Interacts with SEMA4C (PubMed:11134026). Interacts with CXADR (PubMed:15304526). Interacts with KCND2 (PubMed:11923279). Interacts (via first PDZ domain) with CRIPT (PubMed:9581762). Interacts through its first PDZ domain with GRIK2 and KCNA4 (By similarity). Interacts through its second PDZ domain with the PDZ domain of NOS1 or the C-terminus of CAPON (PubMed:23300088). 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 and SIPA1L1 (PubMed:9115257, PubMed:9756850, PubMed:11502259, PubMed:9786987). Interacts through its guanylate kinase-like domain with KIF13B (By similarity). Isoform 2 interacts through an L27 domain with HGS/HRS and the first L27 domain of CASK (By similarity). Interacts with ANKS1B (PubMed:17334360). Interacts with ADR1B (By similarity). May interact with HTR2A (By similarity). Interacts with ADAM22, KLHL17 and LGI1 (PubMed:16054660, PubMed:16990550, PubMed:20089912). Interacts with FRMPD4 (via C-terminus) (PubMed:19118189). Interacts with LRFN1 and LRFN2 (PubMed:16495444, PubMed:16630835). Interacts with LRFN4 (By similarity). 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 (PubMed:23300088). Interacts (via N-terminus tandem pair of PDZ domains) with NOS1 (via N-terminal domain) (PubMed:23300088). Interacts with SHANK3 (By similarity). Interacts with GPR85 (By similarity). Interacts with CACNG2 and MPP2 (via the SH3-Guanylate kinase-like sub-module) (PubMed:27756895). Interacts with ADGRB1 (By similarity). Found in a complex with PRR7 and GRIN1 (PubMed:27458189). Interacts (via PDZ3 domain and to lesser degree via PDZ2 domain) with PRR7 (PubMed:27458189, PubMed:15629447). 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 (By similarity).By similarity24 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248135, 24 interactors
CORUMiP31016
DIPiDIP-29264N
ELMiP31016
IntActiP31016, 352 interactors
MINTiP31016
STRINGi10116.ENSRNOP00000059045

Structurei

Secondary structure

1724
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP31016
SMRiP31016
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31016

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.By similarity
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
InParanoidiP31016
KOiK11828
PhylomeDBiP31016

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 (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P31016-1) [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
RKPPAEKVME 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
ALSFRFGDVL HVIDAGDEEW 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):80,465
Last modified:July 1, 1993 - v1
Checksum:i7922D4E8E0F9AD85
GO
Isoform 2 (identifier: P31016-2)
Also known as: PSD95-beta
Sequence is not available
Length:
Mass (Da):

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2K7F5A0A0G2K7F5_RAT
Disks large homolog 4
Dlg4
729Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61M → L in CAA47103 (PubMed:7680343).Curated1
Sequence conflicti78S → T in CAA47103 (PubMed:7680343).Curated1
Sequence conflicti177 – 182GVGNQH → ALGTSI in CAA47103 (PubMed:7680343).Curated6
Sequence conflicti200A → G in CAA47103 (PubMed:7680343).Curated1
Sequence conflicti254S → T in CAA47103 (PubMed:7680343).Curated1
Sequence conflicti540 – 555LGPTK…LLSEF → SLDPPKTVPTMIFSPSS in CAA47103 (PubMed:7680343).CuratedAdd BLAST16
Sequence conflicti623 – 625GKH → RDQ in AAB38270 (Ref. 4) Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96853 mRNA Translation: AAA41971.1
X66474 mRNA Translation: CAA47103.1
U77090 mRNA Translation: AAB38270.1
PIRiA45436
JH0800
RefSeqiNP_062567.1, NM_019621.1 [P31016-1]
UniGeneiRn.9765

Genome annotation databases

EnsembliENSRNOT00000068493; ENSRNOP00000059045; ENSRNOG00000018526 [P31016-1]
GeneIDi29495
KEGGirno:29495
UCSCiRGD:68424 rat [P31016-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M96853 mRNA Translation: AAA41971.1
X66474 mRNA Translation: CAA47103.1
U77090 mRNA Translation: AAB38270.1
PIRiA45436
JH0800
RefSeqiNP_062567.1, NM_019621.1 [P31016-1]
UniGeneiRn.9765

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BE9X-ray1.82A302-430[»]
1BFEX-ray2.30A302-402[»]
1IU0NMR-A61-151[»]
1IU2NMR-A61-151[»]
1JXMX-ray2.00A430-724[»]
1JXOX-ray2.30A/B430-724[»]
1KJWX-ray1.80A430-724[»]
1QLCNMR-A155-249[»]
1RGRNMR-A62-154[»]
1TP3X-ray1.99A302-402[»]
1TP5X-ray1.54A302-402[»]
1TQ3X-ray1.89A302-402[»]
2KA9NMR-A61-249[»]
2MHONMR-A60-155[»]
2XKXOther22.90A/B1-724[»]
3GSLX-ray2.05A/B61-249[»]
3WP0X-ray2.04A531-713[»]
3WP1X-ray2.80B531-713[»]
5B64X-ray2.70A531-713[»]
5D13X-ray2.15A/B/C/D302-402[»]
5GNVX-ray2.60A531-713[»]
5HDYX-ray1.80A302-402[»]
5HEBX-ray1.65A302-402[»]
5HEDX-ray1.70A302-402[»]
5HETX-ray2.00A302-402[»]
5HEYX-ray1.50A302-402[»]
5HF1X-ray1.75A302-402[»]
5HF4X-ray1.75A302-402[»]
5HFBX-ray1.62A302-402[»]
5HFCX-ray1.85A302-402[»]
5HFDX-ray1.60A302-402[»]
5HFEX-ray1.80A302-402[»]
5HFFX-ray1.75A302-402[»]
5MZ7X-ray1.53A/B/C/D303-402[»]
5W72NMR-A301-402[»]
5YPOX-ray2.29A/B531-713[»]
5YPRX-ray2.35A426-721[»]
ProteinModelPortaliP31016
SMRiP31016
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248135, 24 interactors
CORUMiP31016
DIPiDIP-29264N
ELMiP31016
IntActiP31016, 352 interactors
MINTiP31016
STRINGi10116.ENSRNOP00000059045

Chemistry databases

ChEMBLiCHEMBL3797015

PTM databases

iPTMnetiP31016
PhosphoSitePlusiP31016
SwissPalmiP31016

Proteomic databases

PaxDbiP31016
PRIDEiP31016

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000068493; ENSRNOP00000059045; ENSRNOG00000018526 [P31016-1]
GeneIDi29495
KEGGirno:29495
UCSCiRGD:68424 rat [P31016-1]

Organism-specific databases

CTDi1742
RGDi68424 Dlg4

Phylogenomic databases

eggNOGiKOG0708 Eukaryota
COG0194 LUCA
GeneTreeiENSGT00760000118866
HOGENOMiHOG000232102
HOVERGENiHBG107814
InParanoidiP31016
KOiK11828
PhylomeDBiP31016

Enzyme and pathway databases

ReactomeiR-RNO-399719 Trafficking of AMPA receptors
R-RNO-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-RNO-442729 CREB phosphorylation through the activation of CaMKII
R-RNO-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-RNO-451308 Activation of Ca-permeable Kainate Receptor
R-RNO-5625900 RHO GTPases activate CIT
R-RNO-5673001 RAF/MAP kinase cascade
R-RNO-5682910 LGI-ADAM interactions
R-RNO-6794361 Neurexins and neuroligins
R-RNO-8849932 Synaptic adhesion-like molecules

Miscellaneous databases

EvolutionaryTraceiP31016
PROiPR:P31016

Gene expression databases

BgeeiENSRNOG00000018526 Expressed in 10 organ(s), highest expression level in brain
ExpressionAtlasiP31016 baseline and differential
GenevisibleiP31016 RN

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_RAT
AccessioniPrimary (citable) accession number: P31016
Secondary accession number(s): P97631
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 7, 2018
This is version 209 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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