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FLASH GENE

Symbol

DLG2

contributors: mct - updated : 10-03-2022

HGNC name	discs, large homolog 2, chapsyn-110 (Drosophila)
HGNC id	2901

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three Dlg (DHR/GLGZ/PDZ) motifs, PDZ1 domain forms a crystallographic trimer that is also predicted to be stable in solution
	an SH3 domain
	and a C terminal GUK domain

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to Drosophila tumor suppressor gene,discs large (Dlg)
	homolog to rattus Chapsyn-110
	homolog to C.elegans c25f6.2

intraspecies

homolog to sap97 and psd95

Homologene

FAMILY

MAGUK (membrane-associated guanylate kinase homolog) family of cell junction proteins

CATEGORY

enzyme , signaling

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,cytosolic
text	postsynaptic sites

basic FUNCTION	involved the subcellular targeting of ion channels and glutamate receptors at excitatory synapses
	appears to mediate tyrosine-phosphorylation of the NMDA receptors and synaptic localization of FYN
	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
	might contribute potentially to molecular mechanisms of neuronal damage in brain disorders (brain trauma, seizures, and ischemia)
	DLG4, DLG3, DLG1, and DLG3 are central organizers of the postsynaptic density at excitatory synapses on pyramidal neurons
	DLG4 and DLG2 play critical but distinct roles in synaptic scaling up and down
	scaffolding protein for ionotropic glutamate receptors at excitatory synapses
	E2F8 and DLG2 regulate insulin secretion

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	small molecule transport

PATHWAY

metabolism

signaling

neurotransmission , signal transduction

a component

heterodimerizing with DLG4 and recruited into the same NMDA receptor and Shaker-type potassium channel clusters

INTERACTION

DNA

RNA

small molecule

protein	cytoplasmic tail of NMDA receptor subunit
	potassium channel
	interactions between GLUD2 and DLG2 involve more than the extreme terminus of the receptor
	DLG2 interacted with SSTR4 and affected the level of SSTR4 on cell membrane, which was associated with the ubiquitination
	is an anchoring protein of NMDA receptors
	DLG2 is a direct ZDHHC14 interactor and substrate

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       missense variant (F900V) in DLG2 (which encodes DLG2) that cosegregated with the delayed puberty constitutional   deletion     partial deletion of the DLG2 gene in patients with global developmental delay and intellectual disability

Susceptibility

to schizophrenia Parkinson's disease (PD)

Variant & Polymorphism other	copy number variants indicating loss of function in the DLG2 gene have been associated with markedly increased risk for schizophrenia, autism spectrum disorder, and intellectual disability
	DLG2 rs3793947 AA genotype showed a significantly lower prevalence in female PD patients compared to the female controls

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer overexpression of DLG2 might be a potential therapy for AD

ANIMAL & CELL MODELS

Dlg2+/- rats had reduced supra-linear dendritic integration of synaptic inputs resulting in impaired associative long-term potentiation