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FLASH GENE

Symbol

DLG3

contributors: mct/pgu - updated : 12-10-2017

HGNC name	discs, large homolog 3 (neuroendocrine-dlg, Drosophila)
HGNC id	2902

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MRX90 mental retardation, 90
Location	Xq13.1      Physical location : 69.664.704 - 69.725.337
Synonym name	synapse associated protein 102
	discs, large (Drosophila) homolog 3 (neuroendocrine-dlg)
Synonym symbol(s)	NEDLG, SAP102, KIAA1232, NE-Dlg, MRX, MRX90, PPP1R82, XLMR

DNA

TYPE	functioning gene
STRUCTURE	60.64 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	an N-terminal insert, developmentally regulated at both mRNA and protein levels

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - AR - DXS7113 - MLLT7 - IL2RG - GJB1 - TAF1 - DXS559 - DLG3 - DXS983 - qter

RNA

TRANSCRIPTS	type	messenger

text	alternative splicing of DLG3 regulates dendritic spine morphology, DLG3 containing the N-terminal insert promotes lengthening of dendritic spines and preferentially promotes the formation of synapses at long spines (PMID: 21209193)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_021120 19 splicing 6032 NP_066943 90 817 - 2015 25555912 variant that possesses a C-terminal insert (I2) between the SH3 and GK domains, and is highly enriched at dendritic spines is regulated developmentally NM_020730 14 - 5087 NP_065781 - 512 - 2015 25555912 NM_001166278 12 - 4544 NP_001159750 - 366 - 2015 25555912

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Endocrine neuroendocrine           pancreas         Nervous brain       highly Homo sapiens   nerve       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Muscular striatum cardiac     Nervous peripherous     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a NMDA receptor binding site in the N-terminal domain, which is specific for the GRIN2B subunit
	three Dlg (DHR/GLGZ/PDZ) motifs
	PPXY motifs
	a SH3 domain and a C terminal GUK domain, implicated in stabilization of DLG3
	PDZ, SH3, and guanylate kinase (GK)-like domains, mediate specific protein-protein interactions

mono polymer

octamer

HOMOLOGY

interspecies

homolog to Drosophila tumor suppressor gene,discs large (Dlg)

Homologene

FAMILY

MAGUK (membrane associated guanylate kinase homolog) superfamily

CATEGORY

enzyme , signaling

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	putative negative regulator of cell proliferation, through its interaction with APC, critical for synaptogenesis
	playing a role in the clustering and targeting of NMDA receptors in the postsynaptic density of excitatory synapses
	regulate the synaptic trafficking of distinct glutamate receptor subtypes at different developmental stages, thereby playing necessary roles in excitatory synapse development
	DLG4, DLG2 and DLG3 are thought to have crucial roles in both AMPA receptor trafficking and formation of NMDA receptor-associated signalling complexes involved in synaptic plasticity
	DLG4, DLG3, DLG1, and DLG3 are central organizers of the postsynaptic density at excitatory synapses on pyramidal neurons
	scaffolding protein for ionotropic glutamate receptors at excitatory synapses
	has unique roles in cortical synapse development by mediating EPHB1 and its downstream PAK1 signaling pathway
	is a scaffolding protein abundantly expressed early in development that mediates glutamate receptor trafficking during synaptogenesis
	is proposed to play a role in stabilizing receptors at immature synapses

CELLULAR PROCESS	cell cycle, division
	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

synapse formation mediated by EPHB1/DLG3/PAK1 signaling in the early postnatal brain may be crucial for cognitive development

a component

INTERACTION

DNA

RNA

small molecule

protein	binding to APC
	interacting with EXOC4 involved in the delivery of NMDARs (N-methyl-D-aspartate receptor) to the cell surface in heterologous cells and neurons
	interaction between DLG3 and GRIN2B is PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain independent and is regulated by alternative splicing of DLG3
	exerts a distinct function by recruiting the ubiquitin ligases NEDD4 and NEDD4L through its PPXY motifs (interactions required for DLG3 monoubiquitination, apical membrane recruitment, and tight junction consolidation)
	binds the C-terminal part of the scaffolding protein neurobeachin (NBEA)
	direct binding of NMDA receptors with DLG3 is involved in the efficient targeting of NMDA receptors to the synapses, whereas ligand binding of the PDZ domains is not essential for the synaptic clustering of DLG3
	binds directly to N-methyl-D-aspartate receptors (NMDARs), anchors receptors at synapses, and facilitates transduction of NMDAR signals
	role of DLG3 in the regulation of NMDAR trafficking

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MRX90

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     caused a reduction in the total number of thalamocortical (TC) axons innervating the somatosensory cortex, but did not affect the segregation of barrels tumoral     --low   in human brain Glioblastoma multiforme (GBM)tissue

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS