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P19492 (GRIA3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamate receptor 3

Short name=GluR-3
Alternative name(s):
AMPA-selective glutamate receptor 3
GluR-C
GluR-K3
Glutamate receptor ionotropic, AMPA 3
Short name=GluA3
Gene names
Name:Gria3
Synonyms:Glur3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length888 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity.

Subunit structure

Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Interacts with PRKCABP, GRIP1 and GRIP2. Found in a complex with GRIA1, GRIA2, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.12

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein. Note: Interaction with CNIH2 and CNIH3 promotes cell surface expression. Ref.9

Domain

The M4 transmembrane segment mediates tetramerization and is required for cell surface expression By similarity.

Post-translational modification

Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-615 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-841 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis By similarity.

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.

Sequence similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA3 subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionIon channel
Ligand-gated ion channel
Receptor
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_procession transmembrane transport

Inferred from Biological aspect of Ancestor. Source: GOC

ionotropic glutamate receptor signaling pathway

Inferred from direct assay PubMed 11834304. Source: GOC

regulation of receptor recycling

Inferred from mutant phenotype PubMed 11348590. Source: UniProtKB

response to fungicide

Inferred from expression pattern PubMed 19591855. Source: RGD

response to lithium ion

Inferred from expression pattern PubMed 15269270. Source: UniProtKB

synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentalpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex

Inferred from direct assay Ref.9. Source: UniProtKB

asymmetric synapse

Inferred from direct assay PubMed 12077196. Source: RGD

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from direct assay PubMed 15844209. Source: RGD

dendritic shaft

Inferred from direct assay PubMed 12077196. Source: RGD

dendritic spine

Inferred from direct assay PubMed 11348590. Source: UniProtKB

ionotropic glutamate receptor complex

Traceable author statement PubMed 11836517. Source: UniProtKB

neuronal cell body

Inferred from direct assay PubMed 12077196. Source: RGD

perikaryon

Inferred from direct assay PubMed 15844209. Source: RGD

postsynaptic density

Inferred from direct assay Ref.5. Source: UniProtKB

postsynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein complex

Inferred from physical interaction Ref.5. Source: UniProtKB

synaptic cleft

Inferred from direct assay PubMed 17207780. Source: RGD

terminal bouton

Inferred from direct assay PubMed 15844209. Source: RGD

   Molecular_functionPDZ domain binding

Inferred from physical interaction Ref.5. Source: UniProtKB

alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity

Inferred from direct assay PubMed 11834304. Source: RGD

extracellular-glutamate-gated ion channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

ionotropic glutamate receptor activity

Inferred from direct assay PubMed 11834304. Source: RGD

protein binding

Inferred from physical interaction Ref.5Ref.8PubMed 9697854. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Grip1P978793EBI-77764,EBI-936113
Pick1Q9EP807EBI-77764,EBI-77728

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Flop (identifier: P19492-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Flip (identifier: P19492-2)

The sequence of this isoform differs from the canonical sequence as follows:
     770-771: NA → TP
     780-780: N → S
     784-784: L → I
     801-805: SGGGD → AKDSG

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 888866Glutamate receptor 3
PRO_0000011537

Regions

Topological domain23 – 546524Extracellular By similarity
Transmembrane547 – 56721Helical; By similarity
Topological domain568 – 59629Cytoplasmic By similarity
Intramembrane597 – 61216Helical; Pore-forming; By similarity
Intramembrane613 – 6153 By similarity
Topological domain616 – 6216Cytoplasmic By similarity
Transmembrane622 – 64221Helical; By similarity
Topological domain643 – 817175Extracellular By similarity
Transmembrane818 – 83821Helical; Name=M4; By similarity
Topological domain839 – 88850Cytoplasmic By similarity
Region502 – 5043Glutamate binding
Region680 – 6812Glutamate binding

Sites

Binding site4741Glutamate
Binding site5091Glutamate
Binding site7311Glutamate

Amino acid modifications

Modified residue8711Phosphotyrosine By similarity
Modified residue8811Phosphotyrosine By similarity
Lipidation6151S-palmitoyl cysteine By similarity
Lipidation8411S-palmitoyl cysteine By similarity
Glycosylation571N-linked (GlcNAc...) Potential
Glycosylation2601N-linked (GlcNAc...) Ref.12
Glycosylation3741N-linked (GlcNAc...) Ref.12
Glycosylation4091N-linked (GlcNAc...) Potential
Glycosylation4161N-linked (GlcNAc...) Potential
Disulfide bond85 ↔ 334 Ref.10 Ref.11 Ref.12
Disulfide bond744 ↔ 799 Ref.10 Ref.11 Ref.12

Natural variations

Alternative sequence770 – 7712NA → TP in isoform Flip.
VSP_000119
Alternative sequence7801N → S in isoform Flip.
VSP_000120
Alternative sequence7841L → I in isoform Flip.
VSP_000121
Alternative sequence801 – 8055SGGGD → AKDSG in isoform Flip.
VSP_000122

Experimental info

Sequence conflict517 – 5182KP → NA Ref.2

Secondary structure

........................................................................................................................... 888
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Flop [UniParc].

Last modified February 1, 1991. Version 1.
Checksum: 2981616375661703

FASTA888100,373
        10         20         30         40         50         60 
MGQSVLRAVF FLVLGLLGHS HGGFPNTISI GGLFMRNTVQ EHSAFRFAVQ LYNTNQNTTE 

        70         80         90        100        110        120 
KPFHLNYHVD HLDSSNSFSV TNAFCSQFSR GVYAIFGFYD QMSMNTLTSF CGALHTSFVT 

       130        140        150        160        170        180 
PSFPTDADVQ FVIQMRPALK GAILSLLSYY KWEKFVYLYD TERGFSVLQA IMEAAVQNNW 

       190        200        210        220        230        240 
QVTARSVGNI KDVQEFRRII EEMDRRQEKR YLIDCEVERI NTILEQVVIL GKHSRGYHYM 

       250        260        270        280        290        300 
LANLGFTDIL LERVMHGGAN ITGFQIVNNE NPMVQQFIQR WVRLDEREFP EAKNAPLKYT 

       310        320        330        340        350        360 
SALTHDAILV IAEAFRYLRR QRVDVSRRGS AGDCLANPAV PWSQGIDIER ALKMVQVQGM 

       370        380        390        400        410        420 
TGNIQFDTYG RRTNYTIDVY EMKVSGSRKA GYWNEYERFV PFSDQQISND SSSSENRTIV 

       430        440        450        460        470        480 
VTTILESPYV MYKKNHEQLE GNERYEGYCV DLAYEIAKHV RIKYKLSIVG DGKYGARDPE 

       490        500        510        520        530        540 
TKIWNGMVGE LVYGRADIAV APLTITLVRE EVIDFSKPFM SLGISIMIKK PQKSKPGVFS 

       550        560        570        580        590        600 
FLDPLAYEIW MCIVFAYIGV SVVLFLVSRF SPYEWHLEDN NEEPRDPQSP PDPPNEFGIF 

       610        620        630        640        650        660 
NSLWFSLGAF MQQGCDISPR SLSGRIVGGV WWFFTLIIIS SYTANLAAFL TVERMVSPIE 

       670        680        690        700        710        720 
SAEDLAKQTE IAYGTLDSGS TKEFFRRSKI AVYEKMWSYM KSAEPSVFTK TTADGVARVR 

       730        740        750        760        770        780 
KSKGKFAFLL ESTMNEYIEQ RKPCDTMKVG GNLDSKGYGV ATPKGSALGN AVNLAVLKLN 

       790        800        810        820        830        840 
EQGLLDKLKN KWWYDKGECG SGGGDSKDKT SALSLSNVAG VFYILVGGLG LAMMVALIEF 

       850        860        870        880 
CYKSRAESKR MKLTKNTQNF KPAPATNTQN YATYREGYNV YGTESVKI 

« Hide

Isoform Flip [UniParc].

Checksum: D53A3C20BFB3F620
Show »

FASTA888100,444

References

[1]"A family of AMPA-selective glutamate receptors."
Keinaenen K., Wisden W., Sommer B., Werner P., Herb A., Verdoorn T.A., Sakmann B., Seeburg P.H.
Science 249:556-560(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Molecular cloning and functional expression of glutamate receptor subunit genes."
Boulter J., Hollmann M., O'Shea-Greenfield A., Hartley M., Deneris E.S., Maron C., Heinemann S.F.
Science 249:1033-1037(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Forebrain.
[3]"A family of glutamate receptor genes: evidence for the formation of heteromultimeric receptors with distinct channel properties."
Nakanishi N., Schneider N.A., Axel R.
Neuron 5:569-581(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (VARIANT FLIP).
Tissue: Brain cortex and Hippocampus.
[4]"Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS."
Sommer B., Keinaenen K., Verdoorn T.A., Wisden W., Burnashev N., Herb A., Koehler M., Takagi T., Sakmann B., Seeburg P.H.
Science 249:1580-1585(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS FLIP AND FLOP).
Tissue: Brain.
[5]"Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1."
Xia J., Zhang X., Staudinger J., Huganir R.L.
Neuron 22:179-187(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKCABP.
[6]"GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors."
Dong H., O'Brien R.J., Fung E.T., Lanahan A.A., Worley P.F., Huganir R.L.
Nature 386:279-284(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRIP1.
Tissue: Hippocampus.
[7]"Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo."
Wyszynski M., Valtschanoff J.G., Naisbitt S., Dunah A.W., Kim E., Standaert D.G., Weinberg R., Sheng M.
J. Neurosci. 19:6528-6537(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRIP2.
[8]"AMPA receptor subunit-specific regulation by a distinct family of type II TARPs."
Kato A.S., Siuda E.R., Nisenbaum E.S., Bredt D.S.
Neuron 59:986-996(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CACNG5.
[9]"Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors."
Schwenk J., Harmel N., Zolles G., Bildl W., Kulik A., Heimrich B., Chisaka O., Jonas P., Schulte U., Fakler B., Kloecker N.
Science 323:1313-1319(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[10]"Structure of the S1S2 glutamate binding domain of GLuR3."
Ahmed A.H., Wang Q., Sondermann H., Oswald R.E.
Proteins 75:628-637(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 407-800 IN COMPLEX WITH GLUTAMATE, DISULFIDE BOND.
[11]"Molecular mechanism of flop selectivity and subsite recognition for an AMPA receptor allosteric modulator: structures of GluA2 and GluA3 in complexes with PEPA."
Ahmed A.H., Ptak C.P., Oswald R.E.
Biochemistry 49:2843-2850(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 417-799 IN COMPLEX WITH GLUTAMATE, DISULFIDE BOND.
[12]"Dynamics and allosteric potential of the AMPA receptor N-terminal domain."
Sukumaran M., Rossmann M., Shrivastava I., Dutta A., Bahar I., Greger I.H.
EMBO J. 30:972-982(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 23-403, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION AT ASN-260 AND ASN-374.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M36420 mRNA. Translation: AAA41245.1.
X54656 mRNA. Translation: CAA38466.1.
M38062 mRNA. Translation: AAA63480.1.
M85036 mRNA. Translation: AAA41241.2.
PIRC40170.
RefSeqNP_001106213.1. NM_001112742.1.
NP_116785.2. NM_032990.2.
UniGeneRn.74049.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3DLNX-ray1.91A416-530[»]
A658-799[»]
3DP4X-ray2.11A416-530[»]
A658-799[»]
3LSWX-ray1.75A417-530[»]
3LSXX-ray2.01A417-530[»]
3M3FX-ray2.50A417-530[»]
A658-799[»]
3M3KX-ray1.79A/C/E417-530[»]
A/C/E658-799[»]
3O21X-ray2.20A/B/C/D23-403[»]
3P3WX-ray4.20A/B/C/D23-403[»]
3RT6X-ray2.84B417-530[»]
B658-799[»]
3RT8X-ray2.43A417-530[»]
A658-799[»]
4F1YX-ray1.79A/C417-530[»]
A/C658-799[»]
4F22X-ray2.06A417-530[»]
A658-799[»]
4F29X-ray1.75A417-530[»]
A658-799[»]
4F2OX-ray1.91A417-530[»]
A658-799[»]
4F2QX-ray2.20A417-530[»]
A658-799[»]
4F31X-ray2.29B/D417-530[»]
B/D658-799[»]
4F39X-ray1.83A417-530[»]
A658-799[»]
4F3BX-ray1.82A417-530[»]
A658-799[»]
4F3GX-ray2.06A417-530[»]
A658-799[»]
ProteinModelPortalP19492.
SMRP19492. Positions 415-530, 657-800.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248251. 1 interaction.
IntActP19492. 8 interactions.
MINTMINT-86220.
STRING10116.ENSRNOP00000010367.

Chemistry

BindingDBP19492.
ChEMBLCHEMBL2093871.
GuidetoPHARMACOLOGY446.

PTM databases

PhosphoSiteP19492.

Proteomic databases

PaxDbP19492.
PRIDEP19492.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID29628.
KEGGrno:29628.
UCSCRGD:70958. rat. [P19492-1]

Organism-specific databases

CTD2892.
RGD70958. Gria3.

Phylogenomic databases

eggNOGNOG316680.
HOGENOMHOG000234372.
HOVERGENHBG051839.
KOK05199.
PhylomeDBP19492.

Gene expression databases

GenevestigatorP19492.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSPR00177. NMDARECEPTOR.
SMARTSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMSSF53822. SSF53822. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP19492.
NextBio609848.

Entry information

Entry nameGRIA3_RAT
AccessionPrimary (citable) accession number: P19492
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: July 9, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references