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P48058 (GRIA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:GRIA4
Synonyms:GLUR4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length902 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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. Ref.4

Subunit structure

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.

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein. Cell projectiondendrite. Note: Interaction with CNIH2, CNIH3 and PRKCG promotes cell surface expression By similarity.

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-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.

Phosphorylated at Ser-862 by PRKCG; phosphorylation increases plasma membrane-associated GRI4 expression 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. GRIA4 subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Cell projection
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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processglutamate receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

ion transmembrane transport

Inferred from Biological aspect of Ancestor. Source: GOC

ionotropic glutamate receptor signaling pathway

Inferred from direct assay Ref.4. Source: GOC

synaptic transmission

Traceable author statement. Source: Reactome

synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

transport

Traceable author statement Ref.1. Source: ProtInc

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

Inferred from sequence or structural similarity. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from Biological aspect of Ancestor. Source: RefGenome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

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

Inferred from direct assay Ref.4. Source: UniProtKB

extracellular-glutamate-gated ion channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

ionotropic glutamate receptor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P48058-1)

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 2 (identifier: P48058-2)

The sequence of this isoform differs from the canonical sequence as follows:
     424-433: ESPYVMYKKN → PLMKNPILRN
     434-902: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 902882Glutamate receptor 4
PRO_0000011538

Regions

Topological domain22 – 544523Extracellular By similarity
Transmembrane545 – 56521Helical; By similarity
Topological domain566 – 59227Cytoplasmic By similarity
Intramembrane593 – 60816Helical; Pore-forming; By similarity
Intramembrane609 – 6113 By similarity
Topological domain612 – 6176Cytoplasmic By similarity
Transmembrane618 – 63821Helical; By similarity
Topological domain639 – 813175Extracellular By similarity
Transmembrane814 – 83421Helical; Name=M4; By similarity
Topological domain835 – 90268Cytoplasmic By similarity
Region500 – 5023Glutamate binding By similarity
Region676 – 6772Glutamate binding By similarity

Sites

Binding site4721Glutamate By similarity
Binding site5071Glutamate By similarity
Binding site7271Glutamate By similarity

Amino acid modifications

Modified residue8621Phosphoserine; by PKC/PRKCG By similarity
Lipidation6111S-palmitoyl cysteine By similarity
Lipidation8371S-palmitoyl cysteine By similarity
Glycosylation561N-linked (GlcNAc...) Potential
Glycosylation2581N-linked (GlcNAc...) Potential
Glycosylation3711N-linked (GlcNAc...) Potential
Glycosylation4071N-linked (GlcNAc...) Potential
Glycosylation4141N-linked (GlcNAc...) Potential
Disulfide bond84 ↔ 331 By similarity
Disulfide bond740 ↔ 795 By similarity

Natural variations

Alternative sequence424 – 43310ESPYVMYKKN → PLMKNPILRN in isoform 2.
VSP_042742
Alternative sequence434 – 902469Missing in isoform 2.
VSP_042743

Experimental info

Sequence conflict541S → A in AAA95962. Ref.1
Sequence conflict2731I → T in AAA95962. Ref.1
Sequence conflict327 – 3282NA → KS in AAA95962. Ref.1
Sequence conflict732 – 7332EY → DN in AAA95962. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 16, 2008. Version 2.
Checksum: 7793AEF0AB829FC5

FASTA902100,871
        10         20         30         40         50         60 
MRIISRQIVL LFSGFWGLAM GAFPSSVQIG GLFIRNTDQE YTAFRLAIFL HNTSPNASEA 

        70         80         90        100        110        120 
PFNLVPHVDN IETANSFAVT NAFCSQYSRG VFAIFGLYDK RSVHTLTSFC SALHISLITP 

       130        140        150        160        170        180 
SFPTEGESQF VLQLRPSLRG ALLSLLDHYE WNCFVFLYDT DRGYSILQAI MEKAGQNGWH 

       190        200        210        220        230        240 
VSAICVENFN DVSYRQLLEE LDRRQEKKFV IDCEIERLQN ILEQIVSVGK HVKGYHYIIA 

       250        260        270        280        290        300 
NLGFKDISLE RFIHGGANVT GFQLVDFNTP MVIKLMDRWK KLDQREYPGS ETPPKYTSAL 

       310        320        330        340        350        360 
TYDGVLVMAE TFRSLRRQKI DISRRGNAGD CLANPAAPWG QGIDMERTLK QVRIQGLTGN 

       370        380        390        400        410        420 
VQFDHYGRRV NYTMDVFELK STGPRKVGYW NDMDKLVLIQ DVPTLGNDTA AIENRTVVVT 

       430        440        450        460        470        480 
TIMESPYVMY KKNHEMFEGN DKYEGYCVDL ASEIAKHIGI KYKIAIVPDG KYGARDADTK 

       490        500        510        520        530        540 
IWNGMVGELV YGKAEIAIAP LTITLVREEV IDFSKPFMSL GISIMIKKPQ KSKPGVFSFL 

       550        560        570        580        590        600 
DPLAYEIWMC IVFAYIGVSV VLFLVSRFSP YEWHTEEPED GKEGPSDQPP NEFGIFNSLW 

       610        620        630        640        650        660 
FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA NLAAFLTVER MVSPIESAED 

       670        680        690        700        710        720 
LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE KMWTYMRSAE PSVFTRTTAE GVARVRKSKG 

       730        740        750        760        770        780 
KFAFLLESTM NEYIEQRKPC DTMKVGGNLD SKGYGVATPK GSSLRTPVNL AVLKLSEAGV 

       790        800        810        820        830        840 
LDKLKNKWWY DKGECGPKDS GSKDKTSALS LSNVAGVFYI LVGGLGLAML VALIEFCYKS 

       850        860        870        880        890        900 
RAEAKRMKLT FSEAIRNKAR LSITGSVGEN GRVLTPDCPK AVHTGTAIRQ SSGLAVIASD 


LP 

« Hide

Isoform 2 [UniParc].

Checksum: 0013C833D25B75CE
Show »

FASTA43349,146

References

« Hide 'large scale' references
[1]"Cloning, expression and pharmacological characterization of a human glutamate receptor: hGluR4."
Fletcher E.J., Nutt S.L., Hoo K.H., Elliott C.E., Korczak B., McWhinnie E.A., Kamboj R.K.
Recept. Channels 3:21-31(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins."
Kato A.S., Gill M.B., Ho M.T., Yu H., Tu Y., Siuda E.R., Wang H., Qian Y.W., Nisenbaum E.S., Tomita S., Bredt D.S.
Neuron 68:1082-1096(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS41707.1. [P48058-2]
CCDS8333.1. [P48058-1]
RefSeqNP_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]
UniGeneHs.503743.

3D structure databases

ProteinModelPortalP48058.
SMRP48058. Positions 23-839.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109150. 6 interactions.
IntActP48058. 1 interaction.
MINTMINT-95403.
STRING9606.ENSP00000282499.

Chemistry

BindingDBP48058.
ChEMBLCHEMBL2096670.
DrugBankDB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGY447.

PTM databases

PhosphoSiteP48058.

Polymorphism databases

DMDM218512059.

Proteomic databases

PaxDbP48058.
PRIDEP48058.

Protocols and materials databases

DNASU2893.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282499; ENSP00000282499; ENSG00000152578. [P48058-1]
ENST00000393125; ENSP00000376833; ENSG00000152578. [P48058-2]
ENST00000428631; ENSP00000415551; ENSG00000152578. [P48058-2]
ENST00000530497; ENSP00000435775; ENSG00000152578. [P48058-1]
GeneID2893.
KEGGhsa:2893.
UCSCuc001piu.1. human. [P48058-2]
uc001pix.2. human. [P48058-1]

Organism-specific databases

CTD2893.
GeneCardsGC11P105514.
H-InvDBHIX0026176.
HGNCHGNC:4574. GRIA4.
MIM138246. gene.
neXtProtNX_P48058.
PharmGKBPA28969.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG316680.
HOGENOMHOG000234372.
HOVERGENHBG051839.
InParanoidP48058.
KOK05200.
OMAIGYWNDM.
OrthoDBEOG7C2R0J.
PhylomeDBP48058.
TreeFamTF315232.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
SignaLinkP48058.

Gene expression databases

ArrayExpressP48058.
BgeeP48058.
CleanExHS_GRIA4.
GenevestigatorP48058.

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

ChiTaRSGRIA4. human.
GeneWikiGRIA4.
GenomeRNAi2893.
NextBio11443.
PROP48058.
SOURCESearch...

Entry information

Entry nameGRIA4_HUMAN
AccessionPrimary (citable) accession number: P48058
Secondary accession number(s): Q86XE8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: December 16, 2008
Last modified: July 9, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM