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P48058

- GRIA4_HUMAN

UniProt

P48058 - GRIA4_HUMAN

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Protein
Glutamate receptor 4
Gene
GRIA4, GLUR4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei472 – 4721Glutamate By similarity
Binding sitei507 – 5071Glutamate By similarity
Binding sitei727 – 7271Glutamate By similarity

GO - Molecular functioni

  1. alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Source: UniProtKB
  2. extracellular-glutamate-gated ion channel activity Source: RefGenome
  3. ionotropic glutamate receptor activity Source: UniProtKB

GO - Biological processi

  1. glutamate receptor signaling pathway Source: ProtInc
  2. ion transmembrane transport Source: GOC
  3. ionotropic glutamate receptor signaling pathway Source: GOC
  4. synaptic transmission Source: Reactome
  5. synaptic transmission, glutamatergic Source: RefGenome
  6. transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

ReactomeiREACT_18307. Trafficking of AMPA receptors.
REACT_18338. Activation of AMPA receptors.
REACT_18422. Trafficking of GluR2-containing AMPA receptors.
REACT_20594. Unblocking of NMDA receptor, glutamate binding and activation.
SignaLinkiP48058.

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:GRIA4
Synonyms:GLUR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:4574. GRIA4.

Subcellular locationi

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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 544523Extracellular By similarity
Add
BLAST
Transmembranei545 – 56521Helical; By similarity
Add
BLAST
Topological domaini566 – 59227Cytoplasmic By similarity
Add
BLAST
Intramembranei593 – 60816Helical; Pore-forming; By similarity
Add
BLAST
Intramembranei609 – 6113 By similarity
Topological domaini612 – 6176Cytoplasmic By similarity
Transmembranei618 – 63821Helical; By similarity
Add
BLAST
Topological domaini639 – 813175Extracellular By similarity
Add
BLAST
Transmembranei814 – 83421Helical; Name=M4; By similarity
Add
BLAST
Topological domaini835 – 90268Cytoplasmic By similarity
Add
BLAST

GO - Cellular componenti

  1. alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex Source: UniProtKB
  2. cell junction Source: UniProtKB-KW
  3. dendrite Source: RefGenome
  4. endocytic vesicle membrane Source: Reactome
  5. plasma membrane Source: Reactome
  6. postsynaptic membrane Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28969.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020 Reviewed prediction
Add
BLAST
Chaini21 – 902882Glutamate receptor 4
PRO_0000011538Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi56 – 561N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi84 ↔ 331 By similarity
Glycosylationi258 – 2581N-linked (GlcNAc...) Reviewed prediction
Glycosylationi371 – 3711N-linked (GlcNAc...) Reviewed prediction
Glycosylationi407 – 4071N-linked (GlcNAc...) Reviewed prediction
Glycosylationi414 – 4141N-linked (GlcNAc...) Reviewed prediction
Lipidationi611 – 6111S-palmitoyl cysteine By similarity
Disulfide bondi740 ↔ 795 By similarity
Lipidationi837 – 8371S-palmitoyl cysteine By similarity
Modified residuei862 – 8621Phosphoserine; by PKC/PRKCG By similarity

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.
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

PaxDbiP48058.
PRIDEiP48058.

PTM databases

PhosphoSiteiP48058.

Expressioni

Gene expression databases

ArrayExpressiP48058.
BgeeiP48058.
CleanExiHS_GRIA4.
GenevestigatoriP48058.

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.

Protein-protein interaction databases

BioGridi109150. 6 interactions.
IntActiP48058. 1 interaction.
MINTiMINT-95403.
STRINGi9606.ENSP00000282499.

Structurei

3D structure databases

ProteinModelPortaliP48058.
SMRiP48058. Positions 23-839.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni500 – 5023Glutamate binding By similarity
Regioni676 – 6772Glutamate binding By similarity

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

eggNOGiNOG316680.
HOGENOMiHOG000234372.
HOVERGENiHBG051839.
InParanoidiP48058.
KOiK05200.
OMAiIGYWNDM.
OrthoDBiEOG7C2R0J.
PhylomeDBiP48058.
TreeFamiTF315232.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSiPR00177. NMDARECEPTOR.
SMARTiSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
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. Align

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

MRIISRQIVL LFSGFWGLAM GAFPSSVQIG GLFIRNTDQE YTAFRLAIFL    50
HNTSPNASEA PFNLVPHVDN IETANSFAVT NAFCSQYSRG VFAIFGLYDK 100
RSVHTLTSFC SALHISLITP SFPTEGESQF VLQLRPSLRG ALLSLLDHYE 150
WNCFVFLYDT DRGYSILQAI MEKAGQNGWH VSAICVENFN DVSYRQLLEE 200
LDRRQEKKFV IDCEIERLQN ILEQIVSVGK HVKGYHYIIA NLGFKDISLE 250
RFIHGGANVT GFQLVDFNTP MVIKLMDRWK KLDQREYPGS ETPPKYTSAL 300
TYDGVLVMAE TFRSLRRQKI DISRRGNAGD CLANPAAPWG QGIDMERTLK 350
QVRIQGLTGN VQFDHYGRRV NYTMDVFELK STGPRKVGYW NDMDKLVLIQ 400
DVPTLGNDTA AIENRTVVVT TIMESPYVMY KKNHEMFEGN DKYEGYCVDL 450
ASEIAKHIGI KYKIAIVPDG KYGARDADTK IWNGMVGELV YGKAEIAIAP 500
LTITLVREEV IDFSKPFMSL GISIMIKKPQ KSKPGVFSFL DPLAYEIWMC 550
IVFAYIGVSV VLFLVSRFSP YEWHTEEPED GKEGPSDQPP NEFGIFNSLW 600
FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA NLAAFLTVER 650
MVSPIESAED LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE KMWTYMRSAE 700
PSVFTRTTAE GVARVRKSKG KFAFLLESTM NEYIEQRKPC DTMKVGGNLD 750
SKGYGVATPK GSSLRTPVNL AVLKLSEAGV LDKLKNKWWY DKGECGPKDS 800
GSKDKTSALS LSNVAGVFYI LVGGLGLAML VALIEFCYKS RAEAKRMKLT 850
FSEAIRNKAR LSITGSVGEN GRVLTPDCPK AVHTGTAIRQ SSGLAVIASD 900
LP 902
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei424 – 43310ESPYVMYKKN → PLMKNPILRN in isoform 2.
VSP_042742
Alternative sequencei434 – 902469Missing in isoform 2.
VSP_042743Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541S → A in AAA95962. 1 Publication
Sequence conflicti273 – 2731I → T in AAA95962. 1 Publication
Sequence conflicti327 – 3282NA → KS in AAA95962. 1 Publication
Sequence conflicti732 – 7332EY → DN in AAA95962. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.1. human. [P48058-2]
uc001pix.2. human. [P48058-1]

Polymorphism databases

DMDMi218512059.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS41707.1. [P48058-2 ]
CCDS8333.1. [P48058-1 ]
RefSeqi NP_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 ]
UniGenei Hs.503743.

3D structure databases

ProteinModelPortali P48058.
SMRi P48058. Positions 23-839.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109150. 6 interactions.
IntActi P48058. 1 interaction.
MINTi MINT-95403.
STRINGi 9606.ENSP00000282499.

Chemistry

BindingDBi P48058.
ChEMBLi CHEMBL2096670.
DrugBanki DB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGYi 447.

PTM databases

PhosphoSitei P48058.

Polymorphism databases

DMDMi 218512059.

Proteomic databases

PaxDbi P48058.
PRIDEi P48058.

Protocols and materials databases

DNASUi 2893.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000282499 ; ENSP00000282499 ; ENSG00000152578 . [P48058-1 ]
ENST00000393125 ; ENSP00000376833 ; ENSG00000152578 . [P48058-2 ]
ENST00000428631 ; ENSP00000415551 ; ENSG00000152578 . [P48058-2 ]
ENST00000530497 ; ENSP00000435775 ; ENSG00000152578 . [P48058-1 ]
GeneIDi 2893.
KEGGi hsa:2893.
UCSCi uc001piu.1. human. [P48058-2 ]
uc001pix.2. human. [P48058-1 ]

Organism-specific databases

CTDi 2893.
GeneCardsi GC11P105514.
H-InvDB HIX0026176.
HGNCi HGNC:4574. GRIA4.
MIMi 138246. gene.
neXtProti NX_P48058.
PharmGKBi PA28969.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG316680.
HOGENOMi HOG000234372.
HOVERGENi HBG051839.
InParanoidi P48058.
KOi K05200.
OMAi IGYWNDM.
OrthoDBi EOG7C2R0J.
PhylomeDBi P48058.
TreeFami TF315232.

Enzyme and pathway databases

Reactomei REACT_18307. Trafficking of AMPA receptors.
REACT_18338. Activation of AMPA receptors.
REACT_18422. Trafficking of GluR2-containing AMPA receptors.
REACT_20594. Unblocking of NMDA receptor, glutamate binding and activation.
SignaLinki P48058.

Miscellaneous databases

ChiTaRSi GRIA4. human.
GeneWikii GRIA4.
GenomeRNAii 2893.
NextBioi 11443.
PROi P48058.
SOURCEi Search...

Gene expression databases

ArrayExpressi P48058.
Bgeei P48058.
CleanExi HS_GRIA4.
Genevestigatori P48058.

Family and domain databases

InterProi IPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view ]
Pfami PF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view ]
PRINTSi PR00177. NMDARECEPTOR.
SMARTi SM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view ]
SUPFAMi SSF53822. SSF53822. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiGRIA4_HUMAN
AccessioniPrimary (citable) accession number: P48058
Secondary accession number(s): Q86XE8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: December 16, 2008
Last modified: September 3, 2014
This is version 134 of the entry and version 2 of the sequence. [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

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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