ID   GRIA4_MOUSE             Reviewed;         902 AA.
AC   Q9Z2W8; Q6P9M7;
DT   11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 179.
DE   RecName: Full=Glutamate receptor 4;
DE            Short=GluR-4;
DE            Short=GluR4;
DE   AltName: Full=AMPA-selective glutamate receptor 4;
DE   AltName: Full=GluR-D;
DE   AltName: Full=Glutamate receptor ionotropic, AMPA 4;
DE            Short=GluA4;
DE   Flags: Precursor;
GN   Name=Gria4; Synonyms=Glur4;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J;
RA   Sakimura K., Ikeno K.;
RT   "Mouse glutamate receptor channel alpha4 subunit.";
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=ddY; TISSUE=Spinal cord;
RA   Doi Y., Nishizawa M., Minami T., Ito S.;
RT   "Expression of AMPA-selective glutamate receptors in mouse spinal cord.";
RL   Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PALMITOYLATION AT CYS-837.
RX   PubMed=16129400; DOI=10.1016/j.neuron.2005.06.035;
RA   Hayashi T., Rumbaugh G., Huganir R.L.;
RT   "Differential regulation of AMPA receptor subunit trafficking by
RT   palmitoylation of two distinct sites.";
RL   Neuron 47:709-723(2005).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Receptor for glutamate that functions as a ligand-gated ion
CC       channel in the central nervous system and plays an important role in
CC       excitatory synaptic transmission. L-glutamate acts as an excitatory
CC       neurotransmitter at many synapses in the central nervous system.
CC       Binding of the excitatory neurotransmitter L-glutamate induces a
CC       conformation change, leading to the opening of the cation channel, and
CC       thereby converts the chemical signal to an electrical impulse. The
CC       receptor then desensitizes rapidly and enters a transient inactive
CC       state, characterized by the presence of bound agonist. In the presence
CC       of CACNG4 or CACNG7 or CACNG8, shows resensitization which is
CC       characterized by a delayed accumulation of current flux upon continued
CC       application of glutamate (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homotetramer or heterotetramer of pore-forming glutamate
CC       receptor subunits. Tetramers may be formed by the dimerization of
CC       dimers. Interacts with EPB41L1 via its C-terminus (By similarity).
CC       Found in a complex with GRIA1, GRIA2, GRIA3, CNIH2, CNIH3, CACNG2,
CC       CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 and
CC       PRKCG (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC       Postsynaptic cell membrane; Multi-pass membrane protein. Cell
CC       projection, dendrite. Note=Interaction with CNIH2, CNIH3 and PRKCG
CC       promotes cell surface expression. {ECO:0000250}.
CC   -!- DOMAIN: The M4 transmembrane segment mediates tetramerization and is
CC       required for cell surface expression. {ECO:0000250}.
CC   -!- PTM: Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-611
CC       palmitoylation leads to Golgi retention and decreased cell surface
CC       expression. In contrast, Cys-837 palmitoylation does not affect cell
CC       surface expression but regulates stimulation-dependent endocytosis (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated at Ser-862 by PRKCG; phosphorylation increases
CC       plasma membrane-associated GRI4 expression. {ECO:0000250}.
CC   -!- MISCELLANEOUS: The postsynaptic actions of Glu are mediated by a
CC       variety of receptors that are named according to their selective
CC       agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.
CC   -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC       family. GRIA4 subfamily. {ECO:0000305}.
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DR   EMBL; AB022913; BAA74538.1; -; mRNA.
DR   EMBL; AB079073; BAE06154.1; -; mRNA.
DR   EMBL; BC060697; AAH60697.1; -; mRNA.
DR   CCDS; CCDS22797.1; -.
DR   RefSeq; NP_001106651.1; NM_001113180.1.
DR   RefSeq; NP_001106652.1; NM_001113181.1.
DR   RefSeq; NP_062665.3; NM_019691.4.
DR   AlphaFoldDB; Q9Z2W8; -.
DR   SMR; Q9Z2W8; -.
DR   BioGRID; 200060; 9.
DR   IntAct; Q9Z2W8; 2.
DR   STRING; 10090.ENSMUSP00000027020; -.
DR   ChEMBL; CHEMBL2096617; -.
DR   GlyConnect; 2344; 5 N-Linked glycans (3 sites).
DR   GlyCosmos; Q9Z2W8; 6 sites, 5 glycans.
DR   GlyGen; Q9Z2W8; 7 sites, 5 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Z2W8; -.
DR   PhosphoSitePlus; Q9Z2W8; -.
DR   SwissPalm; Q9Z2W8; -.
DR   MaxQB; Q9Z2W8; -.
DR   PaxDb; 10090-ENSMUSP00000027020; -.
DR   PeptideAtlas; Q9Z2W8; -.
DR   ProteomicsDB; 271163; -.
DR   Antibodypedia; 31872; 524 antibodies from 37 providers.
DR   DNASU; 14802; -.
DR   Ensembl; ENSMUST00000063508.15; ENSMUSP00000066980.8; ENSMUSG00000025892.17.
DR   GeneID; 14802; -.
DR   KEGG; mmu:14802; -.
DR   UCSC; uc009obp.2; mouse.
DR   AGR; MGI:95811; -.
DR   CTD; 2893; -.
DR   MGI; MGI:95811; Gria4.
DR   VEuPathDB; HostDB:ENSMUSG00000025892; -.
DR   eggNOG; KOG1054; Eukaryota.
DR   GeneTree; ENSGT00940000155677; -.
DR   InParanoid; Q9Z2W8; -.
DR   OrthoDB; 511851at2759; -.
DR   Reactome; R-MMU-399710; Activation of AMPA receptors.
DR   Reactome; R-MMU-399719; Trafficking of AMPA receptors.
DR   Reactome; R-MMU-416993; Trafficking of GluR2-containing AMPA receptors.
DR   Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR   Reactome; R-MMU-8849932; Synaptic adhesion-like molecules.
DR   BioGRID-ORCS; 14802; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Gria4; mouse.
DR   PRO; PR:Q9Z2W8; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; Q9Z2W8; Protein.
DR   Bgee; ENSMUSG00000025892; Expressed in cerebellum lobe and 163 other cell types or tissues.
DR   ExpressionAtlas; Q9Z2W8; baseline and differential.
DR   GO; GO:0032281; C:AMPA glutamate receptor complex; IDA:MGI.
DR   GO; GO:0030425; C:dendrite; ISO:MGI.
DR   GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0032983; C:kainate selective glutamate receptor complex; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR   GO; GO:0098839; C:postsynaptic density membrane; ISO:MGI.
DR   GO; GO:0048787; C:presynaptic active zone membrane; ISO:MGI.
DR   GO; GO:0045202; C:synapse; IDA:MGI.
DR   GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR   GO; GO:0004971; F:AMPA glutamate receptor activity; ISS:UniProtKB.
DR   GO; GO:0004970; F:glutamate-gated receptor activity; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; ISO:MGI.
DR   GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO.
DR   GO; GO:0007268; P:chemical synaptic transmission; ISO:MGI.
DR   GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:MGI.
DR   GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; ISO:MGI.
DR   GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISO:MGI.
DR   GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central.
DR   CDD; cd06388; PBP1_iGluR_AMPA_GluR4; 1.
DR   CDD; cd13727; PBP2_iGluR_AMPA_GluR4; 1.
DR   Gene3D; 1.10.287.70; -; 2.
DR   Gene3D; 3.40.50.2300; -; 2.
DR   Gene3D; 3.40.190.10; Periplasmic binding protein-like II; 2.
DR   InterPro; IPR001828; ANF_lig-bd_rcpt.
DR   InterPro; IPR019594; Glu/Gly-bd.
DR   InterPro; IPR001508; Iono_Glu_rcpt_met.
DR   InterPro; IPR015683; Ionotropic_Glu_rcpt.
DR   InterPro; IPR001320; Iontro_rcpt_C.
DR   InterPro; IPR028082; Peripla_BP_I.
DR   InterPro; IPR001638; Solute-binding_3/MltF_N.
DR   PANTHER; PTHR18966:SF100; GLUTAMATE RECEPTOR 4; 1.
DR   PANTHER; PTHR18966; IONOTROPIC GLUTAMATE RECEPTOR; 1.
DR   Pfam; PF01094; ANF_receptor; 1.
DR   Pfam; PF00060; Lig_chan; 1.
DR   Pfam; PF10613; Lig_chan-Glu_bd; 1.
DR   Pfam; PF00497; SBP_bac_3; 1.
DR   PRINTS; PR00177; NMDARECEPTOR.
DR   SMART; SM00918; Lig_chan-Glu_bd; 1.
DR   SMART; SM00079; PBPe; 1.
DR   SUPFAM; SSF53822; Periplasmic binding protein-like I; 1.
DR   SUPFAM; SSF53850; Periplasmic binding protein-like II; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   Genevisible; Q9Z2W8; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Disulfide bond; Glycoprotein; Ion channel;
KW   Ion transport; Ligand-gated ion channel; Lipoprotein; Membrane; Palmitate;
KW   Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW   Signal; Synapse; Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..902
FT                   /note="Glutamate receptor 4"
FT                   /id="PRO_0000011539"
FT   TOPO_DOM        22..544
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        545..565
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        566..592
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        593..608
FT                   /note="Helical; Pore-forming"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        609..611
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        612..617
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        618..638
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        639..813
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        814..834
FT                   /note="Helical; Name=M4"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        835..902
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   BINDING         472
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         500..502
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         507
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         676..677
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   BINDING         727
FT                   /ligand="L-glutamate"
FT                   /ligand_id="ChEBI:CHEBI:29985"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         862
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   LIPID           611
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           837
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000269|PubMed:16129400"
FT   CARBOHYD        52
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        56
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        258
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        371
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        407
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        414
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        84..331
FT                   /evidence="ECO:0000250"
FT   DISULFID        740..795
FT                   /evidence="ECO:0000250"
FT   CONFLICT        630
FT                   /note="F -> G (in Ref. 1; BAA74538)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        765..767
FT                   /note="RTP -> GNA (in Ref. 1; BAA74538)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        776..780
FT                   /note="SEAGV -> NEQGL (in Ref. 1; BAA74538)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        797..801
FT                   /note="PKDSG -> SGGGD (in Ref. 1; BAA74538)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   902 AA;  100847 MW;  39844E5CE634B841 CRC64;
     MRIICRQIVL LFSGFWGLAM GAFPSSVQIG GLFIRNTDQE YTAFRLAIFL HNTSPNASEA
     PFNLVPHVDN IETANSFAVT NAFCSQYSRG VFAIFGLYDK RSVHTLTSFC SALHISLITP
     SFPTEGESQF VLQLRPSLRG ALLSLLDHYE WNCFVFLYDT DRGYSILQAI MEKAGQNGWH
     VSAICVENFN DVSYRQLLEE LDRRQEKKFV IDCEIERLQN ILEQIVSVGK HVKGYHYIIA
     NLGFKDISLE RFIHGGANVT GFQLVDFNTP MVTKLMDRWK KLDQREYPGS ETPPKYTSAL
     TYDGVLVMAE TFRSLRRQKI DISRRGNAGD CLANPAAPWG QGIDMERTLK QVRIQGLTGN
     VQFDHYGRRV NYTMDVFELK STGPRKVGYW NDMDKLVLIQ DAPTLGNDTA AIENRTVVVT
     TIMESPYVMY KKNHEMFEGN DKYEGYCVDL ASEIAKHIGI KYKIAIVPDG KYGARDADTK
     IWNGMVGELV YGKAEIAIAP LTITLVREEV IDFSKPFMSL GISIMIKKPQ KSKPGVFSFL
     DPLAYEIWMC IVFAYIGVSV VLFLVSRFSP YEWHTEEPED GKEGPSDQPP NEFGIFNSLW
     FSLGAFMQQG CDISPRSLSG RIVGGVWWFF TLIIISSYTA NLAAFLTVER MVSPIESAED
     LAKQTEIAYG TLDSGSTKEF FRRSKIAVYE KMWTYMRSAE PSVFTRTTAE GVARVRKSKG
     KFAFLLESTM NEYIEQRKPC DTMKVGGNLD SKGYGVATPK GSSLRTPVNL AVLKLSEAGV
     LDKLKNKWWY DKGECGPKDS GSKDKTSALS LSNVAGVFYI LVGGLGLAML VALIEFCYKS
     RAEAKRMKLT FSEAIRNKAR LSITGSVGEN GRVLTPDCPK AVHTGTAIRQ SSGLAVIASD
     LP
//