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Protein

Glutamate receptor 3

Gene

GRIA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

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.

Caution

It is uncertain whether Met-1 or Met-7 is the initiator.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei480GlutamateBy similarity1
Binding sitei515GlutamateBy similarity1
Binding sitei737GlutamateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • glutamate receptor signaling pathway Source: ProtInc

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport

Enzyme and pathway databases

ReactomeiR-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
SignaLinkiP42263

Protein family/group databases

TCDBi1.A.10.1.4 the glutamate-gated ion channel (gic) family of neurotransmitter receptors

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:GRIA3
Synonyms:GLUR3, GLURC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000125675.17
HGNCiHGNC:4573 GRIA3
MIMi305915 gene
neXtProtiNX_P42263

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 552ExtracellularBy similarityAdd BLAST524
Transmembranei553 – 573HelicalBy similarityAdd BLAST21
Topological domaini574 – 602CytoplasmicBy similarityAdd BLAST29
Intramembranei603 – 618Helical; Pore-formingBy similarityAdd BLAST16
Intramembranei619 – 621By similarity3
Topological domaini622 – 627CytoplasmicBy similarity6
Transmembranei628 – 648HelicalBy similarityAdd BLAST21
Topological domaini649 – 823ExtracellularBy similarityAdd BLAST175
Transmembranei824 – 844Helical; Name=M4By similarityAdd BLAST21
Topological domaini845 – 894CytoplasmicBy similarityAdd BLAST50

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked 94 (MRX94)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. MRX94 patients have moderate mental retardation. Other variable features are macrocephaly, seizures, myoclonic jerks, autistic behavior, asthenic body habitus, distal muscle weakness and hyporeflexia.
See also OMIM:300699
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043484450R → Q in MRX94. 1 PublicationCorresponds to variant dbSNP:rs368568228Ensembl.1
Natural variantiVAR_043485631R → S in MRX94; homomers have minimal or no current; heteromers have altered desensitization kinetics. 1 PublicationCorresponds to variant dbSNP:rs137852351EnsemblClinVar.1
Natural variantiVAR_043486706M → T in MRX94; homomers have minimal or no current; heteromers have altered desensitization kinetics. 1 PublicationCorresponds to variant dbSNP:rs137852352EnsemblClinVar.1
Natural variantiVAR_043487833G → R in MRX94; reduced receptor expression possibly due to rapid degradation. 1 PublicationCorresponds to variant dbSNP:rs137852350EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi2892
MalaCardsiGRIA3
MIMi300699 phenotype
OpenTargetsiENSG00000125675
Orphaneti364028 X-linked intellectual disability due to GRIA3 anomalies
PharmGKBiPA28968

Chemistry databases

ChEMBLiCHEMBL3595
DrugBankiDB04599 Aniracetam
DB05047 CX717
DB00898 Ethanol
DB00142 L-Glutamic Acid
DB01356 Lithium
DB04982 Talampanel
GuidetoPHARMACOLOGYi446

Polymorphism and mutation databases

BioMutaiGRIA3
DMDMi77416864

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000001153629 – 894Glutamate receptor 3Add BLAST866

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi63N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi91 ↔ 340By similarity
Glycosylationi266N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi380N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi415N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi422N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi621S-palmitoyl cysteineBy similarity1
Disulfide bondi750 ↔ 805By similarity
Lipidationi847S-palmitoyl cysteineBy similarity1
Modified residuei877PhosphotyrosineBy similarity1
Modified residuei887PhosphotyrosineBy similarity1

Post-translational modificationi

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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP42263
PaxDbiP42263
PeptideAtlasiP42263
PRIDEiP42263
ProteomicsDBi55501
55502 [P42263-2]

PTM databases

iPTMnetiP42263
PhosphoSitePlusiP42263
SwissPalmiP42263

Expressioni

Gene expression databases

BgeeiENSG00000125675
CleanExiHS_GRIA3
ExpressionAtlasiP42263 baseline and differential
GenevisibleiP42263 HS

Organism-specific databases

HPAiHPA058659

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi109149, 21 interactors
DIPiDIP-46195N
IntActiP42263, 1 interactor
STRINGi9606.ENSP00000264357

Chemistry databases

BindingDBiP42263

Structurei

3D structure databases

ProteinModelPortaliP42263
SMRiP42263
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni508 – 510Glutamate bindingBy similarity3
Regioni686 – 687Glutamate bindingBy similarity2

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1054 Eukaryota
ENOG410XPSH LUCA
GeneTreeiENSGT00910000143978
HOVERGENiHBG051839
InParanoidiP42263
KOiK05199
OMAiVEFFCRS
OrthoDBiEOG091G11CB
PhylomeDBiP42263
TreeFamiTF315232

Family and domain databases

InterProiView protein in InterPro
IPR001828 ANF_lig-bd_rcpt
IPR019594 Glu/Gly-bd
IPR001508 Iono_rcpt_met
IPR001320 Iontro_rcpt
IPR028082 Peripla_BP_I
PfamiView protein in Pfam
PF01094 ANF_receptor, 1 hit
PF00060 Lig_chan, 1 hit
PF10613 Lig_chan-Glu_bd, 1 hit
PRINTSiPR00177 NMDARECEPTOR
SMARTiView protein in SMART
SM00918 Lig_chan-Glu_bd, 1 hit
SM00079 PBPe, 1 hit
SUPFAMiSSF53822 SSF53822, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Flop (identifier: P42263-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MARQKKMGQS VLRAVFFLVL GLLGHSHGGF PNTISIGGLF MRNTVQEHSA
60 70 80 90 100
FRFAVQLYNT NQNTTEKPFH LNYHVDHLDS SNSFSVTNAF CSQFSRGVYA
110 120 130 140 150
IFGFYDQMSM NTLTSFCGAL HTSFVTPSFP TDADVQFVIQ MRPALKGAIL
160 170 180 190 200
SLLGHYKWEK FVYLYDTERG FSILQAIMEA AVQNNWQVTA RSVGNIKDVQ
210 220 230 240 250
EFRRIIEEMD RRQEKRYLID CEVERINTIL EQVVILGKHS RGYHYMLANL
260 270 280 290 300
GFTDILLERV MHGGANITGF QIVNNENPMV QQFIQRWVRL DEREFPEAKN
310 320 330 340 350
APLKYTSALT HDAILVIAEA FRYLRRQRVD VSRRGSAGDC LANPAVPWSQ
360 370 380 390 400
GIDIERALKM VQVQGMTGNI QFDTYGRRTN YTIDVYEMKV SGSRKAGYWN
410 420 430 440 450
EYERFVPFSD QQISNDSASS ENRTIVVTTI LESPYVMYKK NHEQLEGNER
460 470 480 490 500
YEGYCVDLAY EIAKHVRIKY KLSIVGDGKY GARDPETKIW NGMVGELVYG
510 520 530 540 550
RADIAVAPLT ITLVREEVID FSKPFMSLGI SIMIKKPQKS KPGVFSFLDP
560 570 580 590 600
LAYEIWMCIV FAYIGVSVVL FLVSRFSPYE WHLEDNNEEP RDPQSPPDPP
610 620 630 640 650
NEFGIFNSLW FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA
660 670 680 690 700
NLAAFLTVER MVSPIESAED LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE
710 720 730 740 750
KMWSYMKSAE PSVFTKTTAD GVARVRKSKG KFAFLLESTM NEYIEQRKPC
760 770 780 790 800
DTMKVGGNLD SKGYGVATPK GSALRNAVNL AVLKLNEQGL LDKLKNKWWY
810 820 830 840 850
DKGECGSGGG DSKDKTSALS LSNVAGVFYI LVGGLGLAMM VALIEFCYKS
860 870 880 890
RAESKRMKLT KNTQNFKPAP ATNTQNYATY REGYNVYGTE SVKI
Length:894
Mass (Da):101,157
Last modified:October 11, 2005 - v2
Checksum:i178589A870E0D102
GO
Isoform Flip (identifier: P42263-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     776-811: NAVNLAVLKLNEQGLLDKLKNKWWYDKGECGSGGGD → TPVNLAVLKLSEQGILDKLKNKWWYDKGECGAKDSG

Show »
Length:894
Mass (Da):101,228
Checksum:iEB3ED4EBBA353021
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195N → H in AAF61847 (PubMed:10644433).Curated1
Sequence conflicti775R → G in AAA67922 (PubMed:7918660).Curated1
Sequence conflicti775R → G in AAA67923 (PubMed:7918660).Curated1
Sequence conflicti775R → G in CAA57567 (Ref. 2) Curated1
Sequence conflicti775R → G in AAF61847 (PubMed:10644433).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043484450R → Q in MRX94. 1 PublicationCorresponds to variant dbSNP:rs368568228Ensembl.1
Natural variantiVAR_023579525F → L3 PublicationsCorresponds to variant dbSNP:rs1052538Ensembl.1
Natural variantiVAR_043485631R → S in MRX94; homomers have minimal or no current; heteromers have altered desensitization kinetics. 1 PublicationCorresponds to variant dbSNP:rs137852351EnsemblClinVar.1
Natural variantiVAR_043486706M → T in MRX94; homomers have minimal or no current; heteromers have altered desensitization kinetics. 1 PublicationCorresponds to variant dbSNP:rs137852352EnsemblClinVar.1
Natural variantiVAR_043487833G → R in MRX94; reduced receptor expression possibly due to rapid degradation. 1 PublicationCorresponds to variant dbSNP:rs137852350EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053351776 – 811NAVNL…SGGGD → TPVNLAVLKLSEQGILDKLK NKWWYDKGECGAKDSG in isoform Flip. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10302 mRNA Translation: AAA67923.1
U10301 mRNA Translation: AAA67922.1
X82068 mRNA Translation: CAA57567.1
AF159277
, AF159262, AF159263, AF159264, AF159265, AF159266, AF159267, AF159268, AF159269, AF159270, AF159271, AF159272, AF159273, AF159274, AF159275 Genomic DNA Translation: AAF61847.1
AF166365
, AF166362, AF166363, AF166364 Genomic DNA Translation: AAF97857.1
AF167332
, AF166366, AF166367, AF166368, AF166369, AF166370, AF166371, AF166372, AF166373, AF166375 Genomic DNA Translation: AAF97858.1
AF167332
, AF166366, AF166367, AF166368, AF166369, AF166370, AF166371, AF166372, AF166373, AF166374 Genomic DNA Translation: AAF97859.1
AL356213 Genomic DNA No translation available.
AL590139 Genomic DNA No translation available.
Z83848 Genomic DNA No translation available.
Z82899 Genomic DNA No translation available.
AL035426 Genomic DNA No translation available.
CH471107 Genomic DNA Translation: EAX11865.1
CH471107 Genomic DNA Translation: EAX11867.1
CCDSiCCDS14604.1 [P42263-1]
CCDS14605.1 [P42263-2]
PIRiS49460
S50128
S53696
RefSeqiNP_000819.3, NM_000828.4
NP_015564.4, NM_007325.4
UniGeneiHs.377070

Genome annotation databases

EnsembliENST00000541091; ENSP00000446440; ENSG00000125675 [P42263-1]
ENST00000620443; ENSP00000478489; ENSG00000125675 [P42263-2]
ENST00000622768; ENSP00000481554; ENSG00000125675 [P42263-1]
GeneIDi2892
KEGGihsa:2892
UCSCiuc033etl.2 human [P42263-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGRIA3_HUMAN
AccessioniPrimary (citable) accession number: P42263
Secondary accession number(s): D3DTF1
, Q4VXD5, Q4VXD6, Q9HDA0, Q9HDA1, Q9HDA2, Q9P0H1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 11, 2005
Last modified: June 20, 2018
This is version 183 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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