Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P48058

- GRIA4_HUMAN

UniProt

P48058 - GRIA4_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Glutamate receptor 4

Gene

GRIA4

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 – 4721GlutamateBy similarity
Binding sitei507 – 5071GlutamateBy similarity
Binding sitei727 – 7271GlutamateBy 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. ionotropic glutamate receptor signaling pathway Source: GOC
  3. ion transmembrane transport 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

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
  7. vesicle Source: UniProtKB
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 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 902882Glutamate receptor 4PRO_0000011538Add
BLAST

Amino acid modifications

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

BgeeiP48058.
CleanExiHS_GRIA4.
ExpressionAtlasiP48058. baseline and differential.
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.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.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 544523ExtracellularBy similarityAdd
BLAST
Topological domaini566 – 59227CytoplasmicBy similarityAdd
BLAST
Topological domaini612 – 6176CytoplasmicBy similarity
Topological domaini639 – 813175ExtracellularBy similarityAdd
BLAST
Topological domaini835 – 90268CytoplasmicBy similarityAdd
BLAST

Intramembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Intramembranei593 – 60816Helical; Pore-formingBy similarityAdd
BLAST
Intramembranei609 – 6113By similarity

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei545 – 56521HelicalBy similarityAdd
BLAST
Transmembranei618 – 63821HelicalBy similarityAdd
BLAST
Transmembranei814 – 83421Helical; Name=M4By similarityAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni500 – 5023Glutamate bindingBy similarity
Regioni676 – 6772Glutamate bindingBy 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.
GeneTreeiENSGT00760000118920.
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

        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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541S → A in AAA95962. (PubMed:8589990)Curated
Sequence conflicti273 – 2731I → T in AAA95962. (PubMed:8589990)Curated
Sequence conflicti327 – 3282NA → KS in AAA95962. (PubMed:8589990)Curated
Sequence conflicti732 – 7332EY → DN in AAA95962. (PubMed:8589990)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei424 – 43310ESPYVMYKKN → PLMKNPILRN in isoform 2. 1 PublicationVSP_042742
Alternative sequencei434 – 902469Missing in isoform 2. 1 PublicationVSP_042743Add
BLAST

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.
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.
GeneTreei ENSGT00760000118920.
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

Bgeei P48058.
CleanExi HS_GRIA4.
ExpressionAtlasi P48058. baseline and differential.
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: October 29, 2014
This is version 136 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