Human Gene GRIA3 (uc004etr.4) Description and Page Index
  Description: Homo sapiens glutamate receptor, ionotropic, AMPA 3 (GRIA3), transcript variant 2, mRNA.
RefSeq Summary (NM_000828): Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chrX:122,318,096-122,624,766 Size: 306,671 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg19 chrX:122,318,388-122,616,895 Size: 298,508 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:122,318,096-122,624,766)mRNA (may differ from genome)Protein (894 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkHGNCHPRDHuman Cortex Gene ExpressionLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: GRIA3_HUMAN
DESCRIPTION: RecName: Full=Glutamate receptor 3; Short=GluR-3; AltName: Full=AMPA-selective glutamate receptor 3; AltName: Full=GluR-C; AltName: Full=GluR-K3; AltName: Full=Glutamate receptor ionotropic, AMPA 3; Short=GluA3; Flags: Precursor;
FUNCTION: Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist.In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
SUBUNIT: Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Interacts with PRKCABP, GRIP1 and GRIP2 (By similarity). Found in a complex with GRIA1, GRIA2, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 (By similarity).
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Note=Interaction with CNIH2 and CNIH3 promotes cell surface expression (By similarity).
PTM: Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-621 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-847 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).
DISEASE: Defects in GRIA3 are the cause of mental retardation X- linked type 94 (MRX94) [MIM:300699]. Mental retardation is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. MRX94 patients have moderate mental retardation. Other variable features are macrocephaly, seizures, myoclonic jerks, autistic behavior, asthenic body habitus, distal muscle weakness and hyporeflexia.
MISCELLANEOUS: The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.
SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA3 subfamily.
CAUTION: It is uncertain whether Met-1 or Met-7 is the initiator.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GRIA3
CDC HuGE Published Literature: GRIA3
Positive Disease Associations: Citalopram/adverse effects*
Related Studies:
  1. Citalopram/adverse effects*
    Perlis RH, , et al. , Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients., . [PubMed 19295509]

-  MalaCards Disease Associations
  MalaCards Gene Search: GRIA3
Diseases sorted by gene-association score: mental retardation, x-linked, syndromic, wu type* (1550), rasmussen encephalitis (29), canavan disease (7), auditory neuropathy (4), schizophrenia (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 24.78 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 167.95 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -74.00292-0.253 Picture PostScript Text
3' UTR -566.402205-0.257 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001828 - ANF_lig-bd_rcpt
IPR019594 - Glu_rcpt_Glu/Gly-bd
IPR001320 - Iontro_glu_rcpt
IPR001508 - NMDA_rcpt

Pfam Domains:
PF00060 - Ligand-gated ion channel
PF00497 - Bacterial extracellular solute-binding proteins, family 3
PF01094 - Receptor family ligand binding region
PF10613 - Ligated ion channel L-glutamate- and glycine-binding site

SCOP Domains:
53822 - Periplasmic binding protein-like I
53850 - Periplasmic binding protein-like II

ModBase Predicted Comparative 3D Structure on P42263
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 RGDEnsemblFlyBase  
 Protein SequenceProtein SequenceProtein Sequence  
 AlignmentAlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001540 beta-amyloid binding
GO:0004970 ionotropic glutamate receptor activity
GO:0004971 AMPA glutamate receptor activity
GO:0005216 ion channel activity
GO:0005231 excitatory extracellular ligand-gated ion channel activity
GO:0005234 extracellular-glutamate-gated ion channel activity
GO:0038023 signaling receptor activity

Biological Process:
GO:0006811 ion transport
GO:0007215 glutamate receptor signaling pathway
GO:0034220 ion transmembrane transport
GO:0035235 ionotropic glutamate receptor signaling pathway
GO:0060079 excitatory postsynaptic potential

Cellular Component:
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030054 cell junction
GO:0030666 endocytic vesicle membrane
GO:0032281 AMPA glutamate receptor complex
GO:0045202 synapse
GO:0045211 postsynaptic membrane


-  Descriptions from all associated GenBank mRNAs
  X82068 - H.sapiens mRNA for glutamate receptor subunit GluRC.
BC117464 - Homo sapiens glutamate receptor, ionotrophic, AMPA 3, mRNA (cDNA clone MGC:151073 IMAGE:40126015), complete cds.
U10302 - Human glutamate receptor flop isoform (GluR3-flop) mRNA, complete cds.
U10301 - Human glutamate receptor flip isoform (GluR3-flip) mRNA, complete cds.
HQ258659 - Synthetic construct Homo sapiens clone IMAGE:100072689 glutamate receptor, ionotrophic, AMPA 3 (GRIA3) gene, encodes complete protein.
KJ901466 - Synthetic construct Homo sapiens clone ccsbBroadEn_10860 GRIA3 gene, encodes complete protein.
KR711641 - Synthetic construct Homo sapiens clone CCSBHm_00027918 GRIA3 (GRIA3) mRNA, encodes complete protein.
KR711642 - Synthetic construct Homo sapiens clone CCSBHm_00027919 GRIA3 (GRIA3) mRNA, encodes complete protein.
KR711643 - Synthetic construct Homo sapiens clone CCSBHm_00027920 GRIA3 (GRIA3) mRNA, encodes complete protein.
AB384892 - Synthetic construct DNA, clone: pF1KB4082, Homo sapiens GRIA3 gene for glutamate receptor 3 precursor, complete cds, without stop codon, in Flexi system.
AK297136 - Homo sapiens cDNA FLJ51894 complete cds, highly similar to Glutamate receptor 3 precursor.
BC032004 - Homo sapiens glutamate receptor, ionotrophic, AMPA 3, mRNA (cDNA clone IMAGE:4753474), complete cds.
JD082704 - Sequence 63728 from Patent EP1572962.
JD490996 - Sequence 472020 from Patent EP1572962.
JD236865 - Sequence 217889 from Patent EP1572962.
JD066032 - Sequence 47056 from Patent EP1572962.
JD066033 - Sequence 47057 from Patent EP1572962.
JD445447 - Sequence 426471 from Patent EP1572962.
JD442035 - Sequence 423059 from Patent EP1572962.
JD062143 - Sequence 43167 from Patent EP1572962.
JD146544 - Sequence 127568 from Patent EP1572962.
JD496346 - Sequence 477370 from Patent EP1572962.
JD498927 - Sequence 479951 from Patent EP1572962.
JD234330 - Sequence 215354 from Patent EP1572962.
JD331305 - Sequence 312329 from Patent EP1572962.
JD181284 - Sequence 162308 from Patent EP1572962.
JD444955 - Sequence 425979 from Patent EP1572962.
JD421075 - Sequence 402099 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction
hsa04730 - Long-term depression

Reactome (by CSHL, EBI, and GO)

Protein P42263 (Reactome details) participates in the following event(s):

R-HSA-420977 Ca permeable AMPA receptor ligand binding
R-HSA-399712 Activation of Ca permeable AMPA receptors
R-HSA-416320 Trafficking of GluR1-containing AMPA receptors
R-HSA-420980 Activation of Ca permeable AMPA receptors
R-HSA-416985 Trafficking of GluR2-containing AMPA receptors to synapse
R-HSA-420975 Ca impermeable AMPA receptor ligand binding
R-HSA-438037 Membrane depolarization upon activation of Ca impermeable AMPA receptors
R-HSA-399711 Activation of Ca impermeable AMPA receptors
R-HSA-416639 Trafficking of GluR2-containing AMPA receptors to extrasynaptic sites
R-HSA-421007 Endocytosis of Ca impermeable AMPA receptors
R-HSA-8849881 SALM2 associate with AMPA and NMDA receptors
R-HSA-432162 Unblocking of NMDA receptor
R-HSA-399710 Activation of AMPA receptors
R-HSA-399719 Trafficking of AMPA receptors
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-8849932 Synaptic adhesion-like molecules
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity
R-HSA-442755 Activation of NMDA receptor and postsynaptic events
R-HSA-6794362 Protein-protein interactions at synapses
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112316 Neuronal System
R-HSA-112315 Transmission across Chemical Synapses

-  Other Names for This Gene
  Alternate Gene Symbols: D3DTF1, GLUR3, GLURC, GRIA3_HUMAN, NM_000828, NP_000819, P42263, Q4VXD5, Q4VXD6, Q9HDA0, Q9HDA1, Q9HDA2
UCSC ID: uc004etr.4
RefSeq Accession: NM_000828
Protein: P42263 (aka GRIA3_HUMAN or GLR3_HUMAN)
CCDS: CCDS14604.1, CCDS14605.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000828.4
exon count: 16CDS single in 3' UTR: no RNA size: 5195
ORF size: 2685CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 5558.00frame shift in genome: no % Coverage: 99.75
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.