Q62108 · DLG4_MOUSE
- ProteinDisks large homolog 4
- GeneDlg4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids724 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins (PubMed:15358775, PubMed:9853749).
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). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (By similarity).
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). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDisks large homolog 4
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ62108
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Lipid-anchor
Note: 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. Suppression of neuronal activity induces synaptic accumulation and clustering of DLG4.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
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.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 38 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, lipidation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000094561 | 1-724 | Disks large homolog 4 | |||
Sequence: MDCLCIVTTKKYRYQDEDTPPLEHSPAHLPNQANSPPVIVNTDTLEAPGYELQVNGTEGEMEYEEITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGGAAAQDGRLRVNDSILFVNEVDVREVTHSAAVEALKEAGSIVRLYVMRRKPPAEKIIEIKLIKGPKGLGFSIAGGVGNQHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVMHEDAVAALKNTYDVVYLKVAKPSNAYLSDSYAPPDITTSYSQHLDNEISHSSYLGTDYPTAMTPTSPRRYSPVAKDLLGEEDIPREPRRIVIHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDQILSVNGVDLRNASHEQAAIALKNAGQTVTIIAQYKPEEYSRFEAKIHDLREQLMNSSLGSGTASLRSNPKRGFYIRALFDYDKTKDCGFLSQALSFHFGDVLHVIDASDEEWWQARRVHSDSETDDIGFIPSKRRVERREWSRLKAKDWGSSSGSQGREDSVLSYETVTQMEVHYARPIIILGPTKDRANDDLLSEFPDKFGSCVPHTTRPKREYEIDGRDYHFVSSREKMEKDIQAHKFIEAGQYNSHLYGTSVQSVREVAEQGKHCILDVSANAVRRLQAAHLHPIAIFIRPRSLENVLEINKRITEEQARKAFDRATKLEQEFTECFSAIVEGDSFEEIYHKVKRVIEDLSGPYIWVPARERL | ||||||
Lipidation | 3 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Lipidation | 5 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 73 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 142 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 240 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 295 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 415 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 418 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 420 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 422 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 425 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 449 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 480 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 580 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 606 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 654 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 715 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Palmitoylated. Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses. Palmitoylation by ZDHHC2 occurs when the synaptic activity decreases and induces DLG4 synaptic clustering. Palmitoylation by ZDHHC15 regulates trafficking to the postsynaptic density and function in synaptogenesis. 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.
Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the outer plexiform layer of the retina of the eye (at protein level) (PubMed:28334377).
Highly expressed in CA1 stratum oriens and stratum radiatum hippocampal neurons (PubMed:26931375).
Expressed in the striatum and in the cortex (PubMed:25979765).
Highly expressed in CA1 stratum oriens and stratum radiatum hippocampal neurons (PubMed:26931375).
Expressed in the striatum and in the cortex (PubMed:25979765).
Gene expression databases
Interaction
Subunit
Interacts through its PDZ domains with ANO2 and NETO1 (PubMed:19243221, PubMed:19474308).
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 (By similarity) (PubMed:20089912).
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).
Interacts (via PDZ domain 2) with SEMA4F (via PDZ-binding motif); this interaction may promote translocation of DLG4/SAP90 to the membrane (PubMed:11483650).
Interacts with RPH3A and GRIN2A; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (By similarity).
Interacts with ABR and BCR (By similarity).
Interacts with DGKI (via PDZ-binding motif); controls the localization of DGKI to the synapse (By similarity).
Interacts with C9orf72, SMCR8 and RAB39B (PubMed:31651360).
Interacts with ZDHHC5 (PubMed:20178993).
Interacts with PTEN (via PDZ domain-binding motif); the interaction is induced by NMDA and is required for PTEN location at postsynaptic density (By similarity).
Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CACNG8 and CNIH2 (PubMed:33981040).
Interacts with FAM81A; the interaction facilitates condensate formation via liquid-liquid phase separation (PubMed:38452102).
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 (By similarity) (PubMed:20089912).
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).
Interacts (via PDZ domain 2) with SEMA4F (via PDZ-binding motif); this interaction may promote translocation of DLG4/SAP90 to the membrane (PubMed:11483650).
Interacts with RPH3A and GRIN2A; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (By similarity).
Interacts with ABR and BCR (By similarity).
Interacts with DGKI (via PDZ-binding motif); controls the localization of DGKI to the synapse (By similarity).
Interacts with C9orf72, SMCR8 and RAB39B (PubMed:31651360).
Interacts with ZDHHC5 (PubMed:20178993).
Interacts with PTEN (via PDZ domain-binding motif); the interaction is induced by NMDA and is required for PTEN location at postsynaptic density (By similarity).
Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CACNG8 and CNIH2 (PubMed:33981040).
Interacts with FAM81A; the interaction facilitates condensate formation via liquid-liquid phase separation (PubMed:38452102).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 15-35 | Disordered | ||||
Sequence: QDEDTPPLEHSPAHLPNQANS | ||||||
Domain | 65-151 | PDZ 1 | ||||
Sequence: EITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGGAAAQDGRLRVNDSILFVNEVDVREVTHSAAVEALKEAGSIVRLYVMRR | ||||||
Domain | 160-246 | PDZ 2 | ||||
Sequence: EIKLIKGPKGLGFSIAGGVGNQHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVMHEDAVAALKNTYDVVYLKVAKP | ||||||
Domain | 313-393 | PDZ 3 | ||||
Sequence: RIVIHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDQILSVNGVDLRNASHEQAAIALKNAGQTVTIIAQYK | ||||||
Domain | 428-498 | SH3 | ||||
Sequence: KRGFYIRALFDYDKTKDCGFLSQALSFHFGDVLHVIDASDEEWWQARRVHSDSETDDIGFIPSKRRVERRE | ||||||
Domain | 534-709 | Guanylate kinase-like | ||||
Sequence: ARPIIILGPTKDRANDDLLSEFPDKFGSCVPHTTRPKREYEIDGRDYHFVSSREKMEKDIQAHKFIEAGQYNSHLYGTSVQSVREVAEQGKHCILDVSANAVRRLQAAHLHPIAIFIRPRSLENVLEINKRITEEQARKAFDRATKLEQEFTECFSAIVEGDSFEEIYHKVKRVIE |
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 postsynaptic density.
Sequence similarities
Belongs to the MAGUK family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q62108-1
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.
- Name1
- SynonymsPSD95-alpha
- Length724
- Mass (Da)80,472
- Last updated1997-11-01 v1
- Checksum7EFFC99E1FFF90BA
Q62108-2
- Name2
- SynonymsPSD95-beta
- Differences from canonical
- 1-10: MDCLCIVTTK → MSQRPRAPRSALWLLAPPLLRWAPPLLTVLHSDLFQALLDILDYYEACISESQ
Q62108-3
- Name3
- Differences from canonical
- 51-53: Missing
Computationally mapped potential isoform sequences
There are 13 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
J3KMS4 | J3KMS4_MOUSE | Dlg4 | 51 | ||
A0A338P7H1 | A0A338P7H1_MOUSE | Dlg4 | 198 | ||
A0A338P746 | A0A338P746_MOUSE | Dlg4 | 130 | ||
A0A338P713 | A0A338P713_MOUSE | Dlg4 | 205 | ||
A0A338P6H5 | A0A338P6H5_MOUSE | Dlg4 | 273 | ||
A0A338P6L4 | A0A338P6L4_MOUSE | Dlg4 | 254 | ||
A0A338P6I6 | A0A338P6I6_MOUSE | Dlg4 | 764 | ||
A0A338P6E5 | A0A338P6E5_MOUSE | Dlg4 | 664 | ||
E9Q3Z8 | E9Q3Z8_MOUSE | Dlg4 | 238 | ||
B1AR31 | B1AR31_MOUSE | Dlg4 | 242 | ||
G3UZL5 | G3UZL5_MOUSE | Dlg4 | 668 | ||
J3QMR8 | J3QMR8_MOUSE | Dlg4 | 115 | ||
F6TPQ6 | F6TPQ6_MOUSE | Dlg4 | 130 |
Features
Showing features for alternative sequence, sequence conflict.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D50621 EMBL· GenBank· DDBJ | BAA09297.1 EMBL· GenBank· DDBJ | mRNA | ||
AL596185 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC014807 EMBL· GenBank· DDBJ | AAH14807.1 EMBL· GenBank· DDBJ | mRNA |