DLG4 discs large MAGUK scaffold protein 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DLG4provided by HGNC
Official Full Name: discs large MAGUK scaffold protein 4provided by HGNC
Primary source: HGNC:HGNC:2903
See related: Ensembl:ENSG00000132535 MIM:602887; AllianceGenome:HGNC:2903
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MRD62; PSD95; SAP90; SAP-90
Summary: This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Broad expression in brain (RPKM 34.6), testis (RPKM 6.2) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p13.1

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (7187187..7220050, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (7088092..7120961, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (7090506..7123369, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment.
Title: Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment.
Multivalent Tau/PSD-95 interactions arrest in vitro condensates and clusters mimicking the postsynaptic density.
Title: Multivalent Tau/PSD-95 interactions arrest in vitro condensates and clusters mimicking the postsynaptic density.
FMRP, FXR1 protein and Dlg4 mRNA, which are associated with fragile X syndrome, are involved in the ubiquitin-proteasome system.
Title: FMRP, FXR1 protein and Dlg4 mRNA, which are associated with fragile X syndrome, are involved in the ubiquitin-proteasome system.
Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer's disease.
Title: Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer's disease.
Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners.
Title: Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners.
Heat Shock Factor 1 Directly Regulates Postsynaptic Scaffolding PSD-95 in Aging and Huntington's Disease and Influences Striatal Synaptic Density.
Title: Heat Shock Factor 1 Directly Regulates Postsynaptic Scaffolding PSD-95 in Aging and Huntington's Disease and Influences Striatal Synaptic Density.
Interaction between the guanylate kinase domain of PSD-95 and the proline-rich region and microtubule binding repeats 2 and 3 of tau.
Title: Interaction between the guanylate kinase domain of PSD-95 and the proline-rich region and microtubule binding repeats 2 and 3 of tau.
Zinc-chelating postsynaptic density-95 N-terminus impairs its palmitoyl modification.
Title: Zinc-chelating postsynaptic density-95 N-terminus impairs its palmitoyl modification.
PSD-95: An Effective Target for Stroke Therapy Using Neuroprotective Peptides.
Title: PSD-95: An Effective Target for Stroke Therapy Using Neuroprotective Peptides.
DLG4-related synaptopathy: a new rare brain disorder.
Title: DLG4-related synaptopathy: a new rare brain disorder.

Submit: New GeneRIF Correction See all GeneRIFs (74)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual developmental disorder 62 MedGen: C5394083 OMIM: 618793 GeneReviews: DLG4-Related Synaptopathy	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2023-10-10) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2023-10-10) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 induced-neurotoxicity involves upregulation of NR2B and downregulation of PSD-95 expressions in neuron cells	PubMed
	env	HIV-1 gp120-induced synapse loss significantly decreases levels of PSD-95 protein by the ubiquitin-proteasome pathway in the puncta	PubMed
Tat	tat	HIV-1 Tat treatment induces the formation of complexes involving the low-density lipoprotein receptor-related protein (LRP), postsynaptic density protein-95 (PSD-95), and N-methyl-d-aspartic acid (NMDA) receptors at the neuron surface	PubMed
	tat	HIV-1 Tat decreases the scaffolding protein postsynaptic density 95 (PSD95) in synapses via the low-density lipoprotein receptor-related protein (LRP); Tat decreases PSD95 in a concentration-dependent manner	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables D1 dopamine receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables P2Y1 nucleotide receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables PDZ domain binding	ISS Inferred from Sequence or Structural Similarity more info
enables acetylcholine receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables beta-1 adrenergic receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables ionotropic glutamate receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables ionotropic glutamate receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables kinase binding	IDA Inferred from Direct Assay more info	PubMed
enables neuroligin family protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein phosphatase binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein-containing complex binding	ISS Inferred from Sequence or Structural Similarity more info
enables scaffold protein binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in AMPA glutamate receptor clustering	IBA Inferred from Biological aspect of Ancestor more info
involved_in AMPA glutamate receptor clustering	ISS Inferred from Sequence or Structural Similarity more info
involved_in AMPA glutamate receptor clustering	TAS Traceable Author Statement more info	PubMed
involved_in NMDA selective glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to potassium ion	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in dendritic spine morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of protein localization	IDA Inferred from Direct Assay more info	PubMed
involved_in establishment or maintenance of epithelial cell apical/basal polarity	NAS Non-traceable Author Statement more info	PubMed
involved_in learning	TAS Traceable Author Statement more info	PubMed
involved_in locomotory exploration behavior	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of receptor internalization	ISS Inferred from Sequence or Structural Similarity more info
involved_in nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuromuscular process controlling balance	IEA Inferred from Electronic Annotation more info
involved_in neurotransmitter receptor localization to postsynaptic specialization membrane	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cytosolic calcium ion concentration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of excitatory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuron projection arborization	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of synaptic transmission	ISS Inferred from Sequence or Structural Similarity more info
involved_in postsynaptic neurotransmitter receptor diffusion trapping	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to synapse	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to synapse	IDA Inferred from Direct Assay more info	PubMed
involved_in protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in receptor localization to synapse	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of grooming behavior	IEA Inferred from Electronic Annotation more info
involved_in regulation of long-term neuronal synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in social behavior	IEA Inferred from Electronic Annotation more info
involved_in synaptic vesicle maturation	ISS Inferred from Sequence or Structural Similarity more info
involved_in vocalization behavior	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of AMPA glutamate receptor complex	ISS Inferred from Sequence or Structural Similarity more info
located_in adherens junction	NAS Non-traceable Author Statement more info	PubMed
located_in cell junction	ISS Inferred from Sequence or Structural Similarity more info
located_in cerebellar mossy fiber	IEA Inferred from Electronic Annotation more info
located_in cortical cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendrite cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	ISS Inferred from Sequence or Structural Similarity more info
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in excitatory synapse	ISS Inferred from Sequence or Structural Similarity more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in juxtaparanode region of axon	ISS Inferred from Sequence or Structural Similarity more info
is_active_in neuromuscular junction	IBA Inferred from Biological aspect of Ancestor more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in neuron projection terminus	ISS Inferred from Sequence or Structural Similarity more info
located_in neuron spine	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
is_active_in postsynaptic density membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in synaptic vesicle	ISS Inferred from Sequence or Structural Similarity more info
part_of voltage-gated potassium channel complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: disks large homolog 4

Names: Tax interaction protein 15; discs large homolog 4; post-synaptic density protein 95; synapse-associated protein 90

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008391.3 RefSeqGene

Range

7423..37863

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001128827.4 → NP_001122299.1 disks large homolog 4 isoform 2

See identical proteins and their annotated locations for NP_001122299.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains a distinct 5' UTR and 5' coding region and uses an alternate in-frame splice site, compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus and lacks a 3 amino acid internal segment when compared to isoform 1.

Source sequence(s)

AA954439, AC120057, AK307804, AK308533, BC030203, DC336011

Consensus CDS

CCDS45600.1

UniProtKB/TrEMBL

B7Z4H2

Related

ENSP00000307471.6, ENST00000302955.11

Conserved Domains (6) summary

cd12030
Location:427 → 492

SH3_DLG4; Src Homology 3 domain of Disks Large homolog 4

smart00228
Location:307 → 391

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

pfam00595
Location:62 → 146

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam00625
Location:530 → 708

Guanylate_kin; Guanylate kinase

pfam10600
Location:242 → 309

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:10 → 61

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK
NM_001321074.1 → NP_001308003.1 disks large homolog 4 isoform 3

Status: REVIEWED

Source sequence(s)

AC120057, AI571947, BC030203, BC136553, DB064366

Consensus CDS

CCDS92245.1

UniProtKB/TrEMBL

B7Z4H2, B9EGL1

Related

ENSP00000382428.3, ENST00000399510.8

Conserved Domains (7) summary

cd12030
Location:470 → 535

SH3_DLG4; Src Homology 3 domain of Disks Large homolog 4

smart00228
Location:350 → 434

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

pfam00595
Location:105 → 189

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam00625
Location:573 → 751

Guanylate_kin; Guanylate kinase

pfam10600
Location:285 → 352

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:54 → 104

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK

cl02672
Location:26 → 49

L27; L27 domain
NM_001321075.3 → NP_001308004.1 disks large homolog 4 isoform 4

Status: REVIEWED

Source sequence(s)

AC120057, AK293835, BC030203, BG059570, DC336011

Consensus CDS

CCDS82050.1

UniProtKB/Swiss-Prot

B7Z1S1, G5E939, P78352, Q92941, Q9UKK8

UniProtKB/TrEMBL

B7Z4H2

Related

ENSP00000382425.2, ENST00000399506.9

Conserved Domains (6) summary

cd12030
Location:430 → 495

SH3_DLG4; Src Homology 3 domain of Disks Large homolog 4

smart00228
Location:310 → 394

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

pfam00595
Location:65 → 149

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam00625
Location:533 → 711

Guanylate_kin; Guanylate kinase

pfam10600
Location:245 → 312

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:10 → 64

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK
NM_001321076.3 → NP_001308005.1 disks large homolog 4 isoform 5

Status: REVIEWED

Source sequence(s)

AC120057, AI571947, AK299801, BC030203, BP213421

Consensus CDS

CCDS92243.1

UniProtKB/TrEMBL

B7Z4H2, B7Z647

Related

ENSP00000497647.1, ENST00000649520.1

Conserved Domains (5) summary

cd12030
Location:370 → 435

SH3_DLG4; Src Homology 3 domain of Disks Large homolog 4

smart00228
Location:250 → 334

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

pfam00595
Location:5 → 89

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam00625
Location:473 → 651

Guanylate_kin; Guanylate kinase

pfam10600
Location:185 → 252

PDZ_assoc; PDZ-associated domain of NMDA receptors
NM_001321077.3 → NP_001308006.1 disks large homolog 4 isoform 5

Status: REVIEWED

Source sequence(s)

AC120057, AI571947, AK297346, AK299801, BC030203, BP213421

Consensus CDS

CCDS92243.1

UniProtKB/TrEMBL

B7Z4H2, B7Z647

Related

ENSP00000497879.1, ENST00000649186.1

Conserved Domains (5) summary

cd12030
Location:370 → 435

SH3_DLG4; Src Homology 3 domain of Disks Large homolog 4

smart00228
Location:250 → 334

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

pfam00595
Location:5 → 89

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam00625
Location:473 → 651

Guanylate_kin; Guanylate kinase

pfam10600
Location:185 → 252

PDZ_assoc; PDZ-associated domain of NMDA receptors
NM_001365.5 → NP_001356.1 disks large homolog 4 isoform 1

See identical proteins and their annotated locations for NP_001356.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC120057

Consensus CDS

CCDS45599.1

UniProtKB/TrEMBL

B7Z3U2, K7EQM6

Related

ENSP00000497806.3, ENST00000648172.9

Conserved Domains (7) summary

cd12030
Location:473 → 538

SH3_DLG4; Src Homology 3 domain of Disks Large homolog 4

smart00228
Location:353 → 437

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

pfam00595
Location:108 → 192

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam00625
Location:576 → 754

Guanylate_kin; Guanylate kinase

pfam10600
Location:288 → 355

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam10608
Location:54 → 107

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK

cl02672
Location:26 → 49

L27; L27 domain
NM_001369566.3 → NP_001356495.1 disks large homolog 4 isoform 6

Status: REVIEWED

Source sequence(s)

AC120057, AK308533

Consensus CDS

CCDS92244.1

UniProtKB/TrEMBL

A0A3B3IS17, B7Z4H2

Related

ENSP00000497011.1, ENST00000649971.1

Conserved Domains (6) summary

cd12030
Location:403 → 468

SH3_DLG4; Src Homology 3 domain of Disks Large homolog 4

smart00228
Location:283 → 367

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

pfam00625
Location:506 → 684

Guanylate_kin; Guanylate kinase

pfam10600
Location:218 → 285

PDZ_assoc; PDZ-associated domain of NMDA receptors

pfam00595
Location:38 → 122

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam10608
Location:8 → 37

MAGUK_N_PEST; Polyubiquitination (PEST) N-terminal domain of MAGUK

RNA

NR_135527.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) lacks an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC120057, AI571947, AK296357, BC030203, BC136553, DB064366

Related

ENST00000491753.2