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P48058

- GRIA4_HUMAN

UniProt

P48058 - GRIA4_HUMAN

Protein

Glutamate receptor 4

Gene

GRIA4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 2 (16 Dec 2008)
      Previous versions | rss
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    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

    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

    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

    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.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.
    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

    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.
    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

    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 1, 2014
    This is version 135 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