ID   GRIA2_HUMAN             Reviewed;         883 AA.
AC   P42262; Q96FP6;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2002, sequence version 3.
DT   25-JAN-2012, entry version 128.
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   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FLIP), AND VARIANT ARG-607.
RC   TISSUE=Brain;
RX   MEDLINE=94271981; PubMed=8003671;
RA   Sun W., Ferrer-Montiel A.V., Montal M.;
RT   "Primary structure and functional expression of the AMPA/kainate
RT   receptor subunit 2 from human brain.";
RL   NeuroReport 5:441-444(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM FLOP), AND VARIANTS
RP   ARG-607 AND ARG-608.
RC   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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   RNA EDITING OF POSITION 607.
RX   MEDLINE=95016699; PubMed=7523595;
RA   Paschen W., Hedreen J.C., Ross C.A.;
RT   "RNA editing of the glutamate receptor subunits GluR2 and GluR6 in
RT   human brain tissue.";
RL   J. Neurochem. 63:1596-1602(1994).
RN   [4]
RP   IDENTIFICATION (ISOFORM 3).
RX   PubMed=14687553; DOI=10.1016/S0896-6273(03)00722-0;
RA   Kolleker A., Zhu J.J., Schupp B.J., Qin Y., Mack V., Borchardt T.,
RA   Koehr G., Malinow R., Seeburg P.H., Osten P.;
RT   "Glutamatergic plasticity by synaptic delivery of GluR-B(long)-
RT   containing AMPA receptors.";
RL   Neuron 40:1199-1212(2003).
RN   [5]
RP   INTERACTION WITH PICK1.
RX   PubMed=15247289; DOI=10.1074/jbc.M404499200;
RA   Dev K.K., Nakanishi S., Henley J.M.;
RT   "The PDZ domain of PICK1 differentially accepts protein kinase C-alpha
RT   and GluR2 as interacting ligands.";
RL   J. Biol. Chem. 279:41393-41397(2004).
CC   -!- FUNCTION: Ionotropic glutamate receptor. L-glutamate acts as an
CC       excitatory neurotransmitter at many synapses in the central
CC       nervous system. Binding of the excitatory neurotransmitter L-
CC       glutamate induces a conformation change, leading to the opening of
CC       the cation channel, and thereby converts the chemical signal to an
CC       electrical impulse. The receptor then desensitizes rapidly and
CC       enters a transient inactive state, characterized by the presence
CC       of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8,
CC       shows resensitization which is characterized by a delayed
CC       accumulation of current flux upon continued application of
CC       glutamate (By similarity).
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
CC       and CSPG4. Interacts with PICK1 (via PDZ domain). Interacts with
CC       PRKCABP, GRIP1 and GRIP2 (By similarity). Interacts with GRIA1 and
CC       SYNDIG1 (By similarity). Interacts with LRFN1 (By similarity).
CC       Found in a complex with GRIA1, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2,
CC       CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5
CC       (By similarity).
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC       Endoplasmic reticulum membrane; Multi-pass membrane protein (By
CC       similarity). Cell junction, synapse, postsynaptic cell membrane;
CC       Multi-pass membrane protein. Note=Interaction with CACNG2, CNIH2
CC       and CNIH3 promotes cell surface expression (By similarity).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=Flop;
CC         IsoId=P42262-1; Sequence=Displayed;
CC       Name=Flip;
CC         IsoId=P42262-2; Sequence=VSP_000102, VSP_000103, VSP_000104,
CC                                  VSP_000105;
CC       Name=3; Synonyms=Long;
CC         IsoId=P42262-3; Sequence=VSP_029309;
CC   -!- PTM: Palmitoylated. Depalmitoylated upon glutamate stimulation.
CC       Cys-610 palmitoylation leads to Golgi retention and decreased cell
CC       surface expression. In contrast, Cys-836 palmitoylation does not
CC       affect cell surface expression but regulates stimulation-dependent
CC       endocytosis (By similarity).
CC   -!- RNA EDITING: Modified_positions=607; Note=Partially edited. Fully
CC       edited in the brain. Heteromerically expressed edited GLUR2 (R)
CC       receptor complexes are impermeable to calcium, whereas the
CC       unedited (Q) forms are highly permeable to divalent ions.
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 >
CC       kainate.
CC   -!- SIMILARITY: Belongs to the glutamate-gated ion channel
CC       (TC 1.A.10.1) family. GRIA2 subfamily.
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DR   EMBL; L20814; AAA58631.1; -; mRNA.
DR   EMBL; BC010574; AAH10574.1; -; mRNA.
DR   IPI; IPI00030882; -.
DR   IPI; IPI00219216; -.
DR   IPI; IPI00871510; -.
DR   PIR; I58181; I58181.
DR   RefSeq; NP_000817.2; NM_000826.3.
DR   RefSeq; NP_001077088.1; NM_001083619.1.
DR   RefSeq; NP_001077089.1; NM_001083620.1.
DR   UniGene; Hs.32763; -.
DR   PDB; 2WJW; X-ray; 1.80 A; A=25-412.
DR   PDB; 2WJX; X-ray; 4.10 A; A/B/C=25-412.
DR   PDB; 2XHD; X-ray; 1.80 A; A/B=413-795.
DR   PDB; 3R7X; X-ray; 2.10 A; A/B=413-796.
DR   PDB; 3RN8; X-ray; 1.70 A; A/B/C=413-812.
DR   PDB; 3RNN; X-ray; 1.75 A; A/B/C=413-812.
DR   PDBsum; 2WJW; -.
DR   PDBsum; 2WJX; -.
DR   PDBsum; 2XHD; -.
DR   PDBsum; 3R7X; -.
DR   PDBsum; 3RN8; -.
DR   PDBsum; 3RNN; -.
DR   ProteinModelPortal; P42262; -.
DR   SMR; P42262; 25-838.
DR   DIP; DIP-42852N; -.
DR   IntAct; P42262; 1.
DR   MINT; MINT-2791741; -.
DR   STRING; P42262; -.
DR   PhosphoSite; P42262; -.
DR   DMDM; 23831146; -.
DR   PRIDE; P42262; -.
DR   Ensembl; ENST00000264426; ENSP00000264426; ENSG00000120251.
DR   GeneID; 2891; -.
DR   KEGG; hsa:2891; -.
DR   UCSC; uc003ipm.2; human.
DR   CTD; 2891; -.
DR   GeneCards; GC04P158141; -.
DR   HGNC; HGNC:4572; GRIA2.
DR   HPA; CAB006830; -.
DR   HPA; CAB007812; -.
DR   HPA; CAB012981; -.
DR   HPA; HPA008441; -.
DR   MIM; 138247; gene.
DR   neXtProt; NX_P42262; -.
DR   PharmGKB; PA28967; -.
DR   eggNOG; prNOG14111; -.
DR   GeneTree; ENSGT00590000082809; -.
DR   HOVERGEN; HBG051839; -.
DR   OMA; LTGNIKF; -.
DR   OrthoDB; EOG4TB49K; -.
DR   Reactome; REACT_13685; Neuronal System.
DR   DrugBank; DB00142; L-Glutamic Acid.
DR   NextBio; 11429; -.
DR   ArrayExpress; P42262; -.
DR   Bgee; P42262; -.
DR   CleanEx; HS_GRIA2; -.
DR   Genevestigator; P42262; -.
DR   GermOnline; ENSG00000120251; Homo sapiens.
DR   GO; GO:0032281; C:alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex; ISS:UniProtKB.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004971; F:alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity; ISS:UniProtKB.
DR   GO; GO:0005234; F:extracellular-glutamate-gated ion channel activity; IEA:InterPro.
DR   GO; GO:0015277; F:kainate selective glutamate receptor activity; TAS:ProtInc.
DR   GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR   InterPro; IPR001828; ANF_lig-bd_rcpt.
DR   InterPro; IPR019594; Glu_rcpt_Glu/Gly-bd.
DR   InterPro; IPR001320; Iontro_glu_rcpt.
DR   InterPro; IPR001508; NMDA_rcpt.
DR   KO; K05198; -.
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.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW   Complete proteome; Endoplasmic reticulum; Glycoprotein; Ion transport;
KW   Ionic channel; Ligand-gated ion channel; Lipoprotein; Membrane;
KW   Palmitate; Phosphoprotein; Polymorphism; Postsynaptic cell membrane;
KW   Receptor; Reference proteome; RNA editing; Signal; Synapse;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL        1     24       Potential.
FT   CHAIN        25    883       Glutamate receptor 2.
FT                                /FTId=PRO_0000011532.
FT   TOPO_DOM     25    543       Extracellular (Potential).
FT   TRANSMEM    544    564       Helical; (Potential).
FT   TOPO_DOM    565    624       Cytoplasmic (Potential).
FT   TRANSMEM    625    645       Helical; (Potential).
FT   TOPO_DOM    646    812       Extracellular (Potential).
FT   TRANSMEM    813    833       Helical; (Potential).
FT   TOPO_DOM    834    883       Cytoplasmic (Potential).
FT   REGION      499    501       Glutamate binding (By similarity).
FT   REGION      675    676       Glutamate binding (By similarity).
FT   BINDING     506    506       Glutamate (By similarity).
FT   BINDING     726    726       Glutamate (By similarity).
FT   MOD_RES     683    683       Phosphoserine; by PKC (By similarity).
FT   MOD_RES     717    717       Phosphoserine; by PKG (By similarity).
FT   MOD_RES     869    869       Phosphotyrosine (By similarity).
FT   MOD_RES     876    876       Phosphotyrosine (By similarity).
FT   MOD_RES     880    880       Phosphoserine (By similarity).
FT   LIPID       610    610       S-palmitoyl cysteine (By similarity).
FT   LIPID       836    836       S-palmitoyl cysteine (By similarity).
FT   CARBOHYD    256    256       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    370    370       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    406    406       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    413    413       N-linked (GlcNAc...) (Potential).
FT   VAR_SEQ     765    766       NA -> TP (in isoform Flip).
FT                                /FTId=VSP_000102.
FT   VAR_SEQ     775    775       N -> S (in isoform Flip).
FT                                /FTId=VSP_000103.
FT   VAR_SEQ     779    779       L -> V (in isoform Flip).
FT                                /FTId=VSP_000104.
FT   VAR_SEQ     796    800       SGGGD -> AKDSG (in isoform Flip).
FT                                /FTId=VSP_000105.
FT   VAR_SEQ     848    883       VAKNAQNINPSSSQNSQNFATYKEGYNVYGIESVKI -> M
FT                                TLNDAMRNKARLSITGSTGENGRVMTPEFPKAVHAVPYVSP
FT                                GMGMNVSVTDLS (in isoform 3).
FT                                /FTId=VSP_029309.
FT   VARIANT     607    607       Q -> R (in RNA edited version;
FT                                dbSNP:rs17850674).
FT                                /FTId=VAR_000303.
FT   VARIANT     608    608       Q -> R (in dbSNP:rs17850675).
FT                                /FTId=VAR_037055.
FT   CONFLICT    140    140       I -> V (in Ref. 2; AAH10574).
FT   CONFLICT    241    241       G -> E (in Ref. 1; AAA58631).
FT   CONFLICT    764    764       R -> G (in Ref. 1; AAA58631).
FT   STRAND       27     29
FT   STRAND       32     34
FT   HELIX        38     45
FT   TURN         49     51
FT   STRAND       58     65
FT   HELIX        70     82
FT   TURN         94     96
FT   HELIX        97    103
FT   STRAND      111    113
FT   STRAND      125    127
FT   HELIX       136    142
FT   STRAND      147    152
FT   HELIX       159    171
FT   STRAND      174    179
FT   HELIX       188    191
FT   HELIX       193    201
FT   STRAND      206    211
FT   HELIX       213    225
FT   STRAND      234    237
FT   HELIX       247    249
FT   STRAND      256    258
FT   HELIX       268    277
FT   TURN        282    284
FT   HELIX       295    316
FT   HELIX       343    349
FT   TURN        391    393
SQ   SEQUENCE   883 AA;  98821 MW;  6DAB96C76D1D8448 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
     YDAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ VQVEGLSGNI
     KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT ELPSGNDTSG LENKTVVVTT
     ILESPYVMMK KNHEMLEGNE RYEGYCVDLA AEIAKHCGFK YKLTIVGDGK YGARDADTKI
     WNGMVGELVY GKADIAIAPL TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLD
     PLAYEIWMCI VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF
     SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESAEDL
     SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP SVFVRTTAEG VARVRKSKGK
     YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SSLRNAVNLA VLKLNEQGLL
     DKLKNKWWYD KGECGSGGGD SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR
     AEAKRMKVAK NAQNINPSSS QNSQNFATYK EGYNVYGIES VKI
//