GRIA2_PONAB
ID GRIA2_PONAB Reviewed; 883 AA.
AC Q5R4M0;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Glutamate receptor 2;
DE Short=GluR-2;
DE AltName: Full=AMPA-selective glutamate receptor 2;
DE AltName: Full=GluR-B;
DE AltName: Full=GluR-K2;
DE AltName: Full=Glutamate receptor ionotropic, AMPA 2;
DE Short=GluA2;
DE Flags: Precursor;
GN Name=GRIA2; Synonyms=GLUR2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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). Through complex formation
CC with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and
CC the endosomal sorting of the GRIA2 subunit toward recycling and
CC membrane targeting (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P19491}.
CC -!- SUBUNIT: Homotetramer or heterotetramer of pore-forming glutamate
CC receptor subunits. Tetramers may be formed by the dimerization of
CC dimers. May interact with MPP4. Forms a ternary complex with GRIP1 and
CC CSPG4. Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed
CC ATP hydrolysis disrupts binding to ATAD1 and to GRIP1 and leads to
CC AMPAR complex disassembly. Interacts with PRKCABP and GRIP2 (By
CC similarity). Interacts with PICK1 (via PDZ domain) (By similarity).
CC Interacts with GRIA1 and SYNDIG1 (By similarity). Interacts with LRFN1
CC (By similarity). Found in a complex with GRIA1, GRIA3, GRIA4, CNIH2,
CC CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts
CC with CACNG5. Interacts with SNX27 (via PDZ domain); the interaction is
CC required for recycling to the plasma membrane when endocytosed and
CC prevent degradation in lysosomes (By similarity). Interacts with OLFM2.
CC Interacts with AP4B1, AP4E1 and AP4M1; probably indirect it mediates
CC the somatodendritic localization of GRIA2 in neurons (By similarity).
CC Forms a complex with NSG1, GRIP1 and STX12; controls the intracellular
CC fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward
CC recycling and membrane targeting (By similarity). Interacts with
CC IQSEC1; the interaction is required for ARF6 activation (By
CC similarity). {ECO:0000250|UniProtKB:P19491,
CC ECO:0000250|UniProtKB:P23819}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P23819};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P23819}. Endoplasmic
CC reticulum membrane {ECO:0000250}; Multi-pass membrane protein
CC {ECO:0000250}. Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:P23819}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P23819}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:P23819}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P23819}. Note=Interaction with CACNG2, CNIH2 and
CC CNIH3 promotes cell surface expression (By similarity). Displays a
CC somatodendritic localization and is excluded from axons in neurons (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P23819}.
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-610
CC palmitoylation leads to Golgi retention and decreased cell surface
CC expression. In contrast, Cys-836 palmitoylation does not affect cell
CC surface expression but regulates stimulation-dependent endocytosis (By
CC similarity). {ECO:0000250|UniProtKB:P23819}.
CC -!- PTM: Phosphorylation at Tyr-876 is required forc interaction with
CC IQSEC1 and ARF6 activation. {ECO:0000250|UniProtKB:P19491}.
CC -!- PTM: Ubiquitinated by RNF167, leading to its degradation.
CC {ECO:0000250|UniProtKB:P42262}.
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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. GRIA2 subfamily. {ECO:0000305}.
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DR EMBL; CR861226; CAH93296.1; -; mRNA.
DR AlphaFoldDB; Q5R4M0; -.
DR SMR; Q5R4M0; -.
DR STRING; 9601.ENSPPYP00000016932; -.
DR PRIDE; Q5R4M0; -.
DR eggNOG; KOG1054; Eukaryota.
DR InParanoid; Q5R4M0; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004971; F:AMPA glutamate receptor activity; ISS:UniProtKB.
DR GO; GO:0004970; F:ionotropic glutamate receptor activity; ISS:UniProtKB.
DR GO; GO:0015277; F:kainate selective glutamate receptor activity; ISS:UniProtKB.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..883
FT /note="Glutamate receptor 2"
FT /id="PRO_0000011534"
FT TOPO_DOM 25..543
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 544..564
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 565..591
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT INTRAMEM 592..607
FT /note="Helical; Pore-forming"
FT /evidence="ECO:0000250"
FT INTRAMEM 608..610
FT /evidence="ECO:0000250"
FT TOPO_DOM 611..616
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 617..637
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 638..812
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 813..833
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 834..883
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 867..877
FT /note="Required for interaction with IQSEC1"
FT /evidence="ECO:0000250|UniProtKB:P19491"
FT BINDING 471
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 506
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 726
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT MOD_RES 683
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P19491"
FT MOD_RES 717
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000250|UniProtKB:P19491"
FT MOD_RES 860
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23819"
FT MOD_RES 863
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23819"
FT MOD_RES 876
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P23819"
FT MOD_RES 880
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23819"
FT LIPID 610
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 836
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 78..330
FT /evidence="ECO:0000250"
FT DISULFID 739..794
FT /evidence="ECO:0000250"
SQ SEQUENCE 883 AA; 98875 MW; 9A5073527D447A96 CRC64;
MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP
HIDNLEVANS FAVTNAFCSQ FSRGVYAIFG FYDKKSVNTI TSFCGTLHVS FITPSFPTDG
THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV
GNINNDKKDE MYRSLFQDLE LKKERRVILD CERDKVNDIV DQVITIGKHV KGYHYIIANL
GFTDGDLLKI QFGGANVSGF QIVDYDDSLV SKFIERWSTL EEKEYPGAHT TTIKYTSALT
YYAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ VQVEGLSGNI
KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT ELPSGNDTSG LENKTVVVTT
ILESPYVMMK KNHEMLEGNE RYEGYCVDLA AEIAKHCGFK YKLTIAGDGK YGARDADTKI
WNGMVGELVY GKADIAIAPL TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLY
PLAYEIWMCI VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF
SLGAFMRQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESAEDL
SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP SVFVRTTAEG VARVRKSKGK
YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SSLGTPVNLA VLKLSEQGVL
DKLKNKWWYD KGECGAKDSG SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR
AEAKRMKVAK NAQNINPSSS QNSQNFATYK EGYNVYGIES VKI
