GRIA4_MOUSE
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 03-AUG-2022, entry version 170.
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 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; 6.
DR IntAct; Q9Z2W8; 2.
DR STRING; 10090.ENSMUSP00000027020; -.
DR ChEMBL; CHEMBL2096617; -.
DR GlyConnect; 2344; 5 N-Linked glycans (3 sites).
DR GlyGen; Q9Z2W8; 6 sites, 5 N-linked glycans (3 sites).
DR iPTMnet; Q9Z2W8; -.
DR PhosphoSitePlus; Q9Z2W8; -.
DR SwissPalm; Q9Z2W8; -.
DR MaxQB; Q9Z2W8; -.
DR PaxDb; Q9Z2W8; -.
DR PeptideAtlas; Q9Z2W8; -.
DR PRIDE; Q9Z2W8; -.
DR ProteomicsDB; 271163; -.
DR Antibodypedia; 31872; 461 antibodies from 36 providers.
DR DNASU; 14802; -.
DR Ensembl; ENSMUST00000063508; ENSMUSP00000066980; ENSMUSG00000025892.
DR GeneID; 14802; -.
DR KEGG; mmu:14802; -.
DR UCSC; uc009obp.2; mouse.
DR CTD; 2893; -.
DR MGI; MGI:95811; Gria4.
DR VEuPathDB; HostDB:ENSMUSG00000025892; -.
DR eggNOG; KOG1054; Eukaryota.
DR GeneTree; ENSGT00940000155677; -.
DR InParanoid; Q9Z2W8; -.
DR OrthoDB; 188544at2759; -.
DR Reactome; R-MMU-399710; Activation 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 73 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 161 other tissues.
DR ExpressionAtlas; Q9Z2W8; baseline and differential.
DR Genevisible; Q9Z2W8; MM.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IDA:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0099061; C:integral component of postsynaptic density membrane; ISO:MGI.
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: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:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004970; F:ionotropic glutamate receptor activity; ISS:UniProtKB.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated 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 InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR019594; Glu/Gly-bd.
DR InterPro; IPR001508; Iono_rcpt_met.
DR InterPro; IPR001320; Iontro_rcpt.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00060; Lig_chan; 1.
DR Pfam; PF10613; Lig_chan-Glu_bd; 1.
DR PRINTS; PR00177; NMDARECEPTOR.
DR SMART; SM00918; Lig_chan-Glu_bd; 1.
DR SMART; SM00079; PBPe; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
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
