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Protein

Glutamate receptor 4

Gene

GRIA4

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei472GlutamateBy similarity1
Binding sitei507GlutamateBy similarity1
Binding sitei727GlutamateBy 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
SignaLinkiP48058
SIGNORiP48058

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate receptor 4
Short name:
GluR-4
Short name:
GluR4
Alternative name(s):
AMPA-selective glutamate receptor 4
GluR-D
Glutamate receptor ionotropic, AMPA 4
Short name:
GluA4
Gene namesi
Name:GRIA41 PublicationImported
Synonyms:GLUR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000152578.12
HGNCiHGNC:4574 GRIA4
MIMi138246 gene
neXtProtiNX_P48058

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 domaini22 – 544ExtracellularBy similarityAdd BLAST523
Transmembranei545 – 565HelicalBy similarityAdd BLAST21
Topological domaini566 – 592CytoplasmicBy similarityAdd BLAST27
Intramembranei593 – 608Helical; Pore-formingBy similarityAdd BLAST16
Intramembranei609 – 611By similarity3
Topological domaini612 – 617CytoplasmicBy similarity6
Transmembranei618 – 638HelicalBy similarityAdd BLAST21
Topological domaini639 – 813ExtracellularBy similarityAdd BLAST175
Transmembranei814 – 834Helical; Name=M4By similarityAdd BLAST21
Topological domaini835 – 902CytoplasmicBy similarityAdd BLAST68

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Neurodevelopmental disorder with or without seizures and gait abnormalities (NEDSGA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurodevelopmental disorder characterized by global developmental delay apparent from infancy or early childhood, mild to profound intellectual disability, hypertonia early in life, which progresses to spasticity and impaired gait later, and behavioral abnormalities. Some patients may develop seizures of variable severity early in life.
See also OMIM:617864
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080751639T → S in NEDSGA. 1 Publication1
Natural variantiVAR_080752641N → D in NEDSGA. 1 Publication1
Natural variantiVAR_080753643A → G in NEDSGA. 1 Publication1
Natural variantiVAR_080754644A → V in NEDSGA. 1 Publication1
Natural variantiVAR_080755697R → P in NEDSGA; unknown pathological significance. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi2893
MalaCardsiGRIA4
MIMi617864 phenotype
OpenTargetsiENSG00000152578
PharmGKBiPA28969

Chemistry databases

ChEMBLiCHEMBL3190
DrugBankiDB05047 CX717
DB00898 Ethanol
DB00142 L-Glutamic Acid
DB04982 Talampanel
GuidetoPHARMACOLOGYi447

Polymorphism and mutation databases

BioMutaiGRIA4
DMDMi218512059

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001153821 – 902Glutamate receptor 4Add BLAST882

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi56N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi84 ↔ 331By similarity
Glycosylationi258N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi371N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi407N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi414N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi611S-palmitoyl cysteineBy similarity1
Disulfide bondi740 ↔ 795By similarity
Lipidationi837S-palmitoyl cysteineBy similarity1
Modified residuei862Phosphoserine; by PKC/PRKCGBy similarity1

Post-translational modificationi

Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-611 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-837 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).By similarity
Phosphorylated at Ser-862 by PRKCG; phosphorylation increases plasma membrane-associated GRI4 expression.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP48058
PaxDbiP48058
PeptideAtlasiP48058
PRIDEiP48058
ProteomicsDBi55844
55845 [P48058-2]

PTM databases

iPTMnetiP48058
PhosphoSitePlusiP48058

Expressioni

Gene expression databases

BgeeiENSG00000152578 Expressed in 119 organ(s), highest expression level in corpus callosum
CleanExiHS_GRIA4
ExpressionAtlasiP48058 baseline and differential
GenevisibleiP48058 HS

Interactioni

Subunit structurei

Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Interacts with EPB41L1 via its C-terminus (By similarity). Found in a complex with GRIA1, GRIA2, GRIA3, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 and PRKCG (By similarity).By similarity

Protein-protein interaction databases

BioGridi109150, 7 interactors
IntActiP48058, 2 interactors
MINTiP48058
STRINGi9606.ENSP00000282499

Chemistry databases

BindingDBiP48058

Structurei

3D structure databases

ProteinModelPortaliP48058
SMRiP48058
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni500 – 502Glutamate bindingBy similarity3
Regioni676 – 677Glutamate 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
HOGENOMiHOG000234372
HOVERGENiHBG051839
InParanoidiP48058
KOiK05200
OMAiIQFDHYG
OrthoDBiEOG091G11CB
PhylomeDBiP48058
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

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P48058-1) [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
MRIISRQIVL LFSGFWGLAM GAFPSSVQIG GLFIRNTDQE YTAFRLAIFL
60 70 80 90 100
HNTSPNASEA PFNLVPHVDN IETANSFAVT NAFCSQYSRG VFAIFGLYDK
110 120 130 140 150
RSVHTLTSFC SALHISLITP SFPTEGESQF VLQLRPSLRG ALLSLLDHYE
160 170 180 190 200
WNCFVFLYDT DRGYSILQAI MEKAGQNGWH VSAICVENFN DVSYRQLLEE
210 220 230 240 250
LDRRQEKKFV IDCEIERLQN ILEQIVSVGK HVKGYHYIIA NLGFKDISLE
260 270 280 290 300
RFIHGGANVT GFQLVDFNTP MVIKLMDRWK KLDQREYPGS ETPPKYTSAL
310 320 330 340 350
TYDGVLVMAE TFRSLRRQKI DISRRGNAGD CLANPAAPWG QGIDMERTLK
360 370 380 390 400
QVRIQGLTGN VQFDHYGRRV NYTMDVFELK STGPRKVGYW NDMDKLVLIQ
410 420 430 440 450
DVPTLGNDTA AIENRTVVVT TIMESPYVMY KKNHEMFEGN DKYEGYCVDL
460 470 480 490 500
ASEIAKHIGI KYKIAIVPDG KYGARDADTK IWNGMVGELV YGKAEIAIAP
510 520 530 540 550
LTITLVREEV IDFSKPFMSL GISIMIKKPQ KSKPGVFSFL DPLAYEIWMC
560 570 580 590 600
IVFAYIGVSV VLFLVSRFSP YEWHTEEPED GKEGPSDQPP NEFGIFNSLW
610 620 630 640 650
FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA NLAAFLTVER
660 670 680 690 700
MVSPIESAED LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE KMWTYMRSAE
710 720 730 740 750
PSVFTRTTAE GVARVRKSKG KFAFLLESTM NEYIEQRKPC DTMKVGGNLD
760 770 780 790 800
SKGYGVATPK GSSLRTPVNL AVLKLSEAGV LDKLKNKWWY DKGECGPKDS
810 820 830 840 850
GSKDKTSALS LSNVAGVFYI LVGGLGLAML VALIEFCYKS RAEAKRMKLT
860 870 880 890 900
FSEAIRNKAR LSITGSVGEN GRVLTPDCPK AVHTGTAIRQ SSGLAVIASD

LP
Length:902
Mass (Da):100,871
Last modified:December 16, 2008 - v2
Checksum:i7793AEF0AB829FC5
GO
Isoform 2 (identifier: P48058-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     424-433: ESPYVMYKKN → PLMKNPILRN
     434-902: Missing.

Note: No experimental confirmation available.
Show »
Length:433
Mass (Da):49,146
Checksum:i0013C833D25B75CE
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V164G3V164_HUMAN
Glutamate receptor 4
GRIA4 hCG_2032458
884Annotation score:
E9PQY1E9PQY1_HUMAN
Glutamate receptor 4
GRIA4
225Annotation score:
E9PR13E9PR13_HUMAN
Glutamate receptor 4
GRIA4
84Annotation score:
E9PJZ5E9PJZ5_HUMAN
Glutamate receptor 4
GRIA4
82Annotation score:
H0YDL4H0YDL4_HUMAN
Glutamate receptor 4
GRIA4
104Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54S → A in AAA95962 (PubMed:8589990).Curated1
Sequence conflicti273I → T in AAA95962 (PubMed:8589990).Curated1
Sequence conflicti327 – 328NA → KS in AAA95962 (PubMed:8589990).Curated2
Sequence conflicti732 – 733EY → DN in AAA95962 (PubMed:8589990).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080751639T → S in NEDSGA. 1 Publication1
Natural variantiVAR_080752641N → D in NEDSGA. 1 Publication1
Natural variantiVAR_080753643A → G in NEDSGA. 1 Publication1
Natural variantiVAR_080754644A → V in NEDSGA. 1 Publication1
Natural variantiVAR_080755697R → P in NEDSGA; unknown pathological significance. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042742424 – 433ESPYVMYKKN → PLMKNPILRN in isoform 2. 1 Publication10
Alternative sequenceiVSP_042743434 – 902Missing in isoform 2. 1 PublicationAdd BLAST469

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16129 mRNA Translation: AAA95962.1
AP000641 Genomic DNA No translation available.
AP000673 Genomic DNA No translation available.
AP000813 Genomic DNA No translation available.
AP001561 Genomic DNA No translation available.
BC045546 mRNA Translation: AAH45546.1
BC142654 mRNA Translation: AAI42655.1
BC150209 mRNA Translation: AAI50210.1
CCDSiCCDS41707.1 [P48058-2]
CCDS8333.1 [P48058-1]
RefSeqiNP_000820.3, NM_000829.3
NP_001070711.2, NM_001077243.2
NP_001070712.1, NM_001077244.1 [P48058-2]
NP_001106283.1, NM_001112812.1 [P48058-2]
XP_006718886.1, XM_006718823.1 [P48058-1]
UniGeneiHs.503743

Genome annotation databases

EnsembliENST00000282499; ENSP00000282499; ENSG00000152578 [P48058-1]
ENST00000393125; ENSP00000376833; ENSG00000152578 [P48058-2]
ENST00000428631; ENSP00000415551; ENSG00000152578 [P48058-2]
ENST00000530497; ENSP00000435775; ENSG00000152578 [P48058-1]
GeneIDi2893
KEGGihsa:2893
UCSCiuc001piu.2 human [P48058-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16129 mRNA Translation: AAA95962.1
AP000641 Genomic DNA No translation available.
AP000673 Genomic DNA No translation available.
AP000813 Genomic DNA No translation available.
AP001561 Genomic DNA No translation available.
BC045546 mRNA Translation: AAH45546.1
BC142654 mRNA Translation: AAI42655.1
BC150209 mRNA Translation: AAI50210.1
CCDSiCCDS41707.1 [P48058-2]
CCDS8333.1 [P48058-1]
RefSeqiNP_000820.3, NM_000829.3
NP_001070711.2, NM_001077243.2
NP_001070712.1, NM_001077244.1 [P48058-2]
NP_001106283.1, NM_001112812.1 [P48058-2]
XP_006718886.1, XM_006718823.1 [P48058-1]
UniGeneiHs.503743

3D structure databases

ProteinModelPortaliP48058
SMRiP48058
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109150, 7 interactors
IntActiP48058, 2 interactors
MINTiP48058
STRINGi9606.ENSP00000282499

Chemistry databases

BindingDBiP48058
ChEMBLiCHEMBL3190
DrugBankiDB05047 CX717
DB00898 Ethanol
DB00142 L-Glutamic Acid
DB04982 Talampanel
GuidetoPHARMACOLOGYi447

PTM databases

iPTMnetiP48058
PhosphoSitePlusiP48058

Polymorphism and mutation databases

BioMutaiGRIA4
DMDMi218512059

Proteomic databases

EPDiP48058
PaxDbiP48058
PeptideAtlasiP48058
PRIDEiP48058
ProteomicsDBi55844
55845 [P48058-2]

Protocols and materials databases

DNASUi2893
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282499; ENSP00000282499; ENSG00000152578 [P48058-1]
ENST00000393125; ENSP00000376833; ENSG00000152578 [P48058-2]
ENST00000428631; ENSP00000415551; ENSG00000152578 [P48058-2]
ENST00000530497; ENSP00000435775; ENSG00000152578 [P48058-1]
GeneIDi2893
KEGGihsa:2893
UCSCiuc001piu.2 human [P48058-1]

Organism-specific databases

CTDi2893
DisGeNETi2893
EuPathDBiHostDB:ENSG00000152578.12
GeneCardsiGRIA4
H-InvDBiHIX0026176
HGNCiHGNC:4574 GRIA4
MalaCardsiGRIA4
MIMi138246 gene
617864 phenotype
neXtProtiNX_P48058
OpenTargetsiENSG00000152578
PharmGKBiPA28969
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1054 Eukaryota
ENOG410XPSH LUCA
GeneTreeiENSGT00910000143978
HOGENOMiHOG000234372
HOVERGENiHBG051839
InParanoidiP48058
KOiK05200
OMAiIQFDHYG
OrthoDBiEOG091G11CB
PhylomeDBiP48058
TreeFamiTF315232

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
SignaLinkiP48058
SIGNORiP48058

Miscellaneous databases

ChiTaRSiGRIA4 human
GeneWikiiGRIA4
GenomeRNAii2893
PROiPR:P48058
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152578 Expressed in 119 organ(s), highest expression level in corpus callosum
CleanExiHS_GRIA4
ExpressionAtlasiP48058 baseline and differential
GenevisibleiP48058 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiGRIA4_HUMAN
AccessioniPrimary (citable) accession number: P48058
Secondary accession number(s): Q86XE8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: December 16, 2008
Last modified: November 7, 2018
This is version 170 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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