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P19493 (GRIA4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length902 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. Ref.5 Ref.13 Ref.15

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. Isoform 3 interacts with PRKCABP. Found in a complex with GRIA1, GRIA2, GRIA3, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 and PRKCG. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Cell projection › dendrite. Note: Interaction with CNIH2, CNIH3 and PRKCG promotes cell surface expression. Ref.5 Ref.7 Ref.8 Ref.12

Tissue specificity

Detected in cerebellum (at protein level).

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. Ref.7

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 term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processpositive regulation of synaptic transmission, glutamatergic

Inferred from mutant phenotype PubMed 11036266. Source: UniProtKB

regulation of synapse structure and activity

Traceable author statement PubMed 16246117. Source: UniProtKB

response to fungicide

Inferred from expression pattern PubMed 19591855. Source: RGD

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

Inferred from direct assay Ref.12. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

kainate selective glutamate receptor complex

Inferred from direct assay Ref.15. Source: UniProtKB

neuronal cell body

Inferred from direct assay PubMed 11036266. Source: UniProtKB

postsynaptic density

Inferred from direct assay PubMed 11036266. Source: UniProtKB

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

terminal bouton

Inferred from direct assay PubMed 15844209. Source: RGD

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

Inferred from mutant phenotype Ref.1. Source: RGD

extracellular-glutamate-gated ion channel activity

Inferred from electronic annotation. Source: InterPro

kainate selective glutamate receptor activity

Inferred from direct assay Ref.15. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P19493-1)

Also known as: Flop;

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: P19493-2)

Also known as: Flip;

The sequence of this isoform differs from the canonical sequence as follows:
     765-767: GNA → RTP
     776-780: NEQGL → SEAGV
     797-801: SGGGD → PKDSG
Isoform 3 (identifier: P19493-3)

Also known as: 4C flop;

The sequence of this isoform differs from the canonical sequence as follows:
     849-902: LTFSEATRNK...GLAVIASDLP → VAKSAQTFNP...NVYGTESIKI

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 902882Glutamate receptor 4
PRO_0000011540

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; By similarity
Topological domain835 – 90268Cytoplasmic By similarity
Region500 – 5023Glutamate binding
Region676 – 6772Glutamate binding

Sites

Binding site4721Glutamate
Binding site5071Glutamate
Binding site7271Glutamate By similarity

Amino acid modifications

Modified residue8621Phosphoserine; by PKC/PRKCG Ref.7
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...) Ref.5
Glycosylation4141N-linked (GlcNAc...) Ref.5
Disulfide bond84 ↔ 331 By similarity
Disulfide bond740 ↔ 795 Ref.14

Natural variations

Alternative sequence765 – 7673GNA → RTP in isoform 2.
VSP_000123
Alternative sequence776 – 7805NEQGL → SEAGV in isoform 2.
VSP_000124
Alternative sequence797 – 8015SGGGD → PKDSG in isoform 2.
VSP_000125
Alternative sequence849 – 90254LTFSE…ASDLP → VAKSAQTFNPTSSQNTHNLA TYREGYNVYGTESIKI in isoform 3.
VSP_000126

Experimental info

Mutagenesis4071N → Q: No effect on surface expression and channel activity; when associated with Q-414. Ref.5
Mutagenesis4141N → Q: No effect on surface expression and channel activity; when associated with Q-407. Ref.5
Sequence conflict111 – 1122SA → RR in AAA41242. Ref.2
Sequence conflict4541I → S in AAA41242. Ref.2
Sequence conflict7341T → I in AAA41242. Ref.2
Sequence conflict8551T → I in AAA41242. Ref.2

Secondary structure

1 ..................................................................................................................... 902
Helix Strand Turn

Details...

Sequences

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

Last modified February 1, 1991. Version 1.
Checksum: 873D1B4C710C4459

FASTA902100,758
        10         20         30         40         50         60 
MRIICRQIVL 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 MVTKLMDRWK KLDQREYPGS ETPPKYTSAL 

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

       370        380        390        400        410        420 
VQFDHYGRRV NYTMDVFELK STGPRKVGYW NDMDKLVLIQ DMPTLGNDTA 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 NEYTEQRKPC DTMKVGGNLD SKGYGVATPK GSSLGNAVNL AVLKLNEQGL 

       790        800        810        820        830        840 
LDKLKNKWWY DKGECGSGGG DSKDKTSALS LSNVAGVFYI LVGGLGLAML VALIEFCYKS 

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


LP

« Hide

Isoform 2 (Flip) [UniParc].

Checksum: EB2AEF26FD237199
Show »

FASTA902100,883
Isoform 3 (4C flop) [UniParc].

Checksum: 00B47FD9B55E38C2
Show »

FASTA88499,184

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] (ISOFORM 1).
Tissue: Brain.
[2]"Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development."
Bettler B., Boulter J., Hermans-Borgmeyer I., O'Shea-Greenfield A., Deneris E.S., Moll C., Borgmeyer U., Hollmann M., Heinemann S.F.
Neuron 5:583-595(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"Molecular cloning and development analysis of a new glutamate receptor subunit isoform in cerebellum."
Gallo V., Upson L.M., Hayes W.P., Vyklicky L. Jr., Winters C.A., Buonanno A.
J. Neurosci. 12:1010-1023(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Strain: Sprague-Dawley.
Tissue: Brain.
[5]"Characterization of the functional role of the N-glycans in the AMPA receptor ligand-binding domain."
Pasternack A., Coleman S.K., Fethiere J., Madden D.R., LeCaer J.P., Rossier J., Pasternack M., Keinaenen K.
J. Neurochem. 84:1184-1192(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-407 AND ASN-414, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF ASN-407 AND ASN-414.
[6]"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 (ISOFORM 3).
[7]"Protein kinase C gamma associates directly with the GluR4 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit. Effect on receptor phosphorylation."
Correia S.S., Duarte C.B., Faro C.J., Pires E.V., Carvalho A.L.
J. Biol. Chem. 278:6307-6313(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-862, INTERACTION WITH PRKCG, SUBCELLULAR LOCATION.
[8]"Surface expression of GluR-D AMPA receptor is dependent on an interaction between its C-terminal domain and a 4.1 protein."
Coleman S.K., Cai C., Mottershead D.G., Haapalahti J.-P., Keinaenen K.
J. Neurosci. 23:798-806(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH EPB41L1.
[9]"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.
[10]"Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5."
Soto D., Coombs I.D., Renzi M., Zonouzi M., Farrant M., Cull-Candy S.G.
Nat. Neurosci. 12:277-285(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CACNG5.
[11]Erratum
Soto D., Coombs I.D., Renzi M., Zonouzi M., Farrant M., Cull-Candy S.G.
Nat. Neurosci. 12:808-808(2009)
[12]"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.
[13]"Correlating AMPA receptor activation and cleft closure across subunits: crystal structures of the GluR4 ligand-binding domain in complex with full and partial agonists."
Gill A., Birdsey-Benson A., Jones B.L., Henderson L.P., Madden D.R.
Biochemistry 47:13831-13841(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 416-795 IN COMPLEX WITH GLUTAMATE AND DIHYDROKAINIC ACID, FUNCTION, SUBUNIT.
[14]"Molecular mechanism of agonist recognition by the ligand-binding core of the ionotropic glutamate receptor 4."
Kasper C., Frydenvang K., Naur P., Gajhede M., Pickering D.S., Kastrup J.S.
FEBS Lett. 582:4089-4094(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 415-796 IN COMPLEX WITH GLUTAMATE, AMPA BINDING, DISULFIDE BOND.
[15]"Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors."
Birdsey-Benson A., Gill A., Henderson L.P., Madden D.R.
J. Neurosci. 30:1463-1470(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 416-795 IN COMPLEX WITH GLUTAMATE AND DIHYDROKAINIC ACID, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M36421 mRNA. Translation: AAA41246.1.
M85037 mRNA. Translation: AAA41242.1.
M38063 mRNA. Translation: AAA63481.1.
S94371 mRNA. Translation: AAB21763.1.
IPIIPI00195445.
IPI00231131.
IPI00231132.
PIRA44839.
D40170.
RefSeqNP_001106655.1. NM_001113184.1.
NP_058959.2. NM_017263.2.
UniGeneRn.10938.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EN3X-ray2.43A416-795[»]
3EPEX-ray1.85A/B416-795[»]
3FASX-ray1.40A/B415-796[»]
3FATX-ray1.90A/B/C415-796[»]
3KEIX-ray1.90A/B416-795[»]
3KFMX-ray2.20A416-795[»]
4GPAX-ray2.25A22-401[»]
ProteinModelPortalP19493.
SMRP19493. Positions 413-528, 653-796.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-41142N.
MINTMINT-86166.

Protein family/group databases

TCDB1.A.10.1.2. glutamate-gated ion channel (GIC) family of neurotransmitter receptors.

PTM databases

PhosphoSiteP19493.

Proteomic databases

PaxDbP19493.
PRIDEP19493.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID29629.
KEGGrno:29629.
UCSCRGD:61863. rat.

Organism-specific databases

CTD2893.
RGD61863. Gria4.

Phylogenomic databases

eggNOGNOG316680.
HOGENOMHOG000234372.
HOVERGENHBG051839.
InParanoidP19493.
KOK05200.
OrthoDBEOG4DBTD0.

Gene expression databases

ArrayExpressP19493.
GenevestigatorP19493.
GermOnlineENSRNOG00000006957. Rattus norvegicus.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
[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]
ProtoNetSearch...

Other

BindingDBP19493.
ChEMBLCHEMBL3505.
EvolutionaryTraceP19493.
NextBio609852.

Entry information

Entry nameGRIA4_RAT
AccessionPrimary (citable) accession number: P19493
Secondary accession number(s): Q64241
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: April 3, 2013
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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