Gene Report

Basic Information

Approved Symbol	GRIA2
Approved Name	glutamate receptor, ionotropic, AMPA 2
Previous Symbol	GLUR2
Symbol Alias	GluA2, GLURB
Location	4q32.1
Position	chr4:158141736-158287227 (+)
External Links	Entrez Gene: 2891 Ensembl: ENSG00000120251 UCSC: uc003ipl.4 HGNC ID: 4572
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between GRIA2 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
GRIA2	Teyssier, 2011	patients and normal controls		Expression of DeltaFOSB and GRIA2 was significantly up-regul...... Expression of DeltaFOSB and GRIA2 was significantly up-regulated ( approximately 1.60) in the BA 46 of MDD patients. More...

Positive relationships between GRIA2 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
GRIA2		Brodmann area 46(BA 46)	brain morphology and function	Teyssier, 2011	patients and normal controls		Expression of DeltaFOSB and GRIA2 was significantly up-regul...... Expression of DeltaFOSB and GRIA2 was significantly up-regulated (¡Ö1.60) in the BA 46 of MDD patients More...

Positive relationship network of GRIA2 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between GRIA2 and MDD (count: 0)

Negative relationships between GRIA2 and other components at different levels (count: 0)

GRIA2 related SNPs in MK4MDD (count: 0)

GRIA2 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Glutamate receptor 2	P42262	0(0/0)	Gene mapped

GRIA2 related GO terms (count: 15)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0007268	synaptic transmission	biological process	TAS
GO:0045211	postsynaptic membrane	cellular component	IEA
GO:0030054	cell junction	cellular component	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005789	endoplasmic reticulum membrane	cellular component	IEA
GO:0030666	endocytic vesicle membrane	cellular component	TAS
GO:0008066	glutamate receptor activity	molecular function	TAS[1311100]
GO:0005886	plasma membrane	cellular component	TAS
GO:0035235	ionotropic glutamate receptor signaling pathway	biological process	IDA
GO:0032281	alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex	cellular component	ISS
GO:0004971	alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity	molecular function	ISS
GO:0005234	extracellular-glutamate-gated ion channel activity	molecular function	IEA
GO:0005887	integral to plasma membrane	cellular component	ISS
GO:0007165	signal transduction	biological process	TAS[8003671]
GO:0015277	kainate selective glutamate receptor activity	molecular function	ISS
GO:0004970	ionotropic glutamate receptor activity	molecular function	IDA

GRIA2 related KEGG pathways (count: 4)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04730	long term_depression	Long-term depression	Cerebellar long-term depression (LTD), thought to be a molec...... Cerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and Purkinje cells (PCs) induced by the conjunctive activation of PFs and climbing fiber (CF). Multiple signal transduction pathways have been shown to be involved in this process. Activation of PFs terminating on spines in dendritic branchlets leads to glutamate release and activation of both AMPA and mGluRs. Activation of CFs, which make multiple synaptic contacts on proximal dendrites, also via AMPA receptors, opens voltage-gated calcium channels (VGCCs) and causes a generalized influx of calcium. These cellular signals, generated from two different synaptic origins, trigger a cascade of events culminating in a phosphorylation-dependent, long-term reduction in AMPA receptor sensitivity at the PF-PC synapse. This may take place either through receptor internalization and/or through receptor desensitization. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05014	amyotrophic lateral_sclerosis_als	Amyotrophic lateral sclerosis (ALS)	Amyotrophic lateral sclerosis (ALS) is a progressive, lethal...... Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The hallmark of this disease is the selective death of motor neurons in the brain and spinal cord, leading to paralysis of voluntary muscles. Mutant superoxide dismutase 1 (SOD1), as seen in some familial amyotrophic lateral sclerosis (FALS) cases, may be toxic because it is unstable, forming aggregates in the motor neuron cytoplasm, axoplasm and mitochondria. Within mitochondria, mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2, affect mitochondrial import by interfering with the translocation machinery (TOM/TIM), and generate toxic free radicals (ROS) via aberrant superoxide chemistry. These changes may then result in abnormal mitochondrial energy metabolism, Ca2+ handling, and release of pro-apoptotic factors. Reactive oxygen species (ROS), produced within mitochondria, inhibit the function of EAAT2, the main glial glutamate transporter protein, responsible for most of the reuptake of synaptically released glutamate. Glutamate excess causes neurotoxicity by increasing intracellular calcium, which enhances oxidative stress and mitochondrial damage. Mutant SOD1 can also trigger oxidative reactions by various means including by increasing levels of peroxynitrite, which can then cause damage through the formation of hydroxyl radicals or via nitration of tyrosine residues on proteins. Nitration may target neurofilament proteins, disrupting their phosphorylation and affecting axonal transport. Collectively, these mechanisms (or a combination thereof) are predicted to disturb cellular homeostasis (within glial and/or motor neurons), ultimately triggering motor neuron death. More...
hsa04080	neuroactive ligand_receptor_interaction	Neuroactive ligand-receptor interaction
hsa04720	long term_potentiation	Long-term potentiation	Hippocampal long-term potentiation (LTP), a long-lasting inc...... Hippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippocampus induces glutamate release and activation of glutamate receptors in dendritic spines. A large increase in i resulting from influx through NMDA receptors leads to constitutive activation of CaM kinase II (CaM KII). Constitutively active CaM kinase II phosphorylates AMPA receptors, resulting in potentiation of the ionic conductance of AMPA receptors. Early-phase LTP (E-LTP) expression is due, in part, to this phosphorylation of the AMPA receptor. It is hypothesized that postsynaptic Ca2+ increases generated through NMDA receptors activate several signal transduction pathways including the Erk/MAP kinase and cAMP regulatory pathways. The convergence of these pathways at the level of the CREB/CRE transcriptional pathway may increase expression of a family of genes required for late-phase LTP (L-LTP). More...

GRIA2 related BioCarta pathways (count: 0)

GRIA2 related Reactome pathways (count: 5)

ID	Name	Description
Gene mapped Reactome pathways
REACT_18422	trafficking of_glur2_containing_ampa_receptors	Trafficking of GluR2-containing receptors is governed by pro...... Trafficking of GluR2-containing receptors is governed by protein protein interactions that are regulated by phosphorylation events. GluR2 binds NSF and AP2 in the proximal C terminal region and binds PICK and GRIP1/2 in the extreme C terminal region. GluR2 interaction with NSF is necessary to maintain the synaptic levels of GluR2-containing AMPA receptors both at basal levels and under conditions of synaptic activity. GluR2 interaction with GRIP helps anchor AMPA receptors at the synapse. Phosphorylation of GluR2 at S880 disrupts GRIP interaction but allows binding of PICK. PICK is activated by Ca sensitive Protein kinase C :768-75) More...
REACT_15370	neuroransmitter receptor_binding_and_downstream_transmission_in_the_postsynaptic_cell	The neurotransmitter in the synaptic cleft released by the p...... The neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein coupled receptors that function to transmit the signals from the post-synaptic membrane to the cell body. More...
REACT_18307	trafficking of_ampa_receptors	Repetitive presynaptic activity causes long lasting changes ...... Repetitive presynaptic activity causes long lasting changes in the postsynaptic transmission by changing the type and the number of AMPA receptors. These changes are brought about by trafficking mechanisms that are mainly controlled by activity dependent phosphorylation/desphosphorylation of the GluR1/GluR2 subunits. More...
REACT_13477	transmission across_chemical_synapses	Chemical synapses are specialized junctions that are used fo...... Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell. More...
REACT_20563	activation of_nmda_receptor_upon_glutamate_binding_and_postsynaptic_events	NMDA receptors are a subtype of ionotropic glutamate recepto...... NMDA receptors are a subtype of ionotropic glutamate receptors that are specifically activated by a glutamate agonist N-methyl-D-aspartate (NMDA). Activation of NMDA receptor involves opening of the ion channel that allows the influx of Ca2+. NMDA receptors are central to activity dependent changes in synaptic strength and are predominantly involved in the synaptic plasticity that pertain to learning and memory. A unique feature of NMDA receptor unlike other glutamate receptors is the requirement of dual activation of the NMDA receptor, which require both voltage dependent and ligand dependent activation. At resting membrane potential the NMDA receptors are blocked by Mg2+. The voltage dependent Mg2+ block is relieved upon depolarization of the post-synpatic membrane. The ligand dependent activation of the NMDA receptor requires co-activation by two ligands, namely glutamate and glycine. NMDA receptors are coincidence detector, and are activated only if there is simultaneous activation of both pre and post-synaptic cell. Upon activation NMDA receptors allow the influx of Ca2+ that initiates various molecular signaling cascades that are involved in the process of learning and memory. More...

GRIA2 related interactors from protein-protein interaction data in HPRD (count: 9)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
GRIA2	GRIA3	Yes	in vitro	14687553
GRIA2	GRIP2	No	in vivo;yeast 2-hybrid	9768844
GRIA2	DRD2	Yes	in vitro;in vivo	15858065
GRIA2	PRKCA	No	in vivo	11466413 , 10501226 , 12805550 , 11007883 , 8848293 , 12058067
GRIA2	PICK1	No	in vivo;yeast 2-hybrid	10027300
GRIA2	SQSTM1	No	in vitro;in vivo	19004011
GRIA2	NSF	No	in vitro;in vivo;yeast 2-hybrid	9697855
GRIA2	SPTAN1	No	in vivo	10576550
GRIA2	SDCBP	No	in vitro;yeast 2-hybrid	11891216

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped Reactome pathways