GRIK1_HUMAN
ID GRIK1_HUMAN Reviewed; 918 AA.
AC P39086; Q13001; Q86SU9;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Glutamate receptor ionotropic, kainate 1;
DE Short=GluK1;
DE AltName: Full=Excitatory amino acid receptor 3;
DE Short=EAA3;
DE AltName: Full=Glutamate receptor 5;
DE Short=GluR-5;
DE Short=GluR5;
DE Flags: Precursor;
GN Name=GRIK1; Synonyms=GLUR5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=8260617; DOI=10.1097/00001756-199309150-00014;
RA Gregor P., O'Hara B.F., Yang X., Uhl G.R.;
RT "Expression and novel subunit isoforms of glutamate receptor genes GluR5
RT and GluR6.";
RL NeuroReport 4:1343-1346(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RX PubMed=8589992;
RA Korczak B., Nutt S.L., Fletcher E.J., Hoo K.H., Elliott C.E., Rampersad V.,
RA McWhinnie E.A., Kamboj R.K.;
RT "cDNA cloning and functional properties of human glutamate receptor EAA3
RT (GluR5) in homomeric and heteromeric configuration.";
RL Recept. Channels 3:41-49(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Erythroleukemia;
RA Langer A., Xu D., Kuehcke K., Fehse B., Abdallah S., Lother H.;
RT "Myeloid progenitor cell growth and apoptosis involves known and cell-
RT specific ionotropic glutamate receptors.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP RNA EDITING OF POSITION 636.
RC TISSUE=Brain;
RX PubMed=7696618; DOI=10.1097/00001756-199412000-00055;
RA Nutt S.L., Kamboj R.K.;
RT "RNA editing of human kainate receptor subunits.";
RL NeuroReport 5:2625-2629(1994).
RN [5]
RP VARIANTS VAL-332; GLN-862 AND SER-902.
RX PubMed=11702055; DOI=10.1097/00041444-200109000-00005;
RA Shibata H., Joo A., Fujii Y., Tani A., Makino C., Hirata N., Kikuta R.,
RA Ninomiya H., Tashiro N., Fukumaki Y.;
RT "Association study of polymorphisms in the GluR5 kainate receptor gene
RT (GRIK1) with schizophrenia.";
RL Psychiatr. Genet. 11:139-144(2001).
CC -!- FUNCTION: Ionotropic glutamate receptor. L-glutamate acts as an
CC excitatory neurotransmitter at many synapses in the central nervous
CC system. Binding of the excitatory neurotransmitter L-glutamate induces
CC a conformation change, leading to the opening of the cation channel,
CC and 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. May be involved
CC in the transmission of light information from the retina to the
CC hypothalamus.
CC -!- SUBUNIT: Homotetramer or heterotetramer of pore-forming glutamate
CC receptor subunits. Tetramers may be formed by the dimerization of
CC dimers (Probable). The unedited version (Q) assembles into a functional
CC kainate-gated homomeric channel, whereas the edited version (R) is
CC unable to produce channel activity when expressed alone. Both edited
CC and unedited versions can form functional channels with GRIK4 and
CC GRIK5. Interacts with KLHL17 (By similarity). {ECO:0000250,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Postsynaptic cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=GluR5-1D;
CC IsoId=P39086-1; Sequence=Displayed;
CC Name=2; Synonyms=EAA3A;
CC IsoId=P39086-2; Sequence=VSP_000127, VSP_000128;
CC -!- TISSUE SPECIFICITY: Most abundant in the cerebellum and the
CC suprachiasmatic nuclei (SCN) of the hypothalamus.
CC -!- RNA EDITING: Modified_positions=636 {ECO:0000269|PubMed:7696618};
CC Note=Partially edited.;
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 domoate > kainate > L-glutamate =
CC quisqualate > CNQX = DNQX > AMPA > dihydrokainate > NMDA.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. GRIK1 subfamily. {ECO:0000305}.
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DR EMBL; L19058; AAA52568.1; -; mRNA.
DR EMBL; U16125; AAA95961.1; -; mRNA.
DR EMBL; AJ249208; CAC80546.1; -; mRNA.
DR CCDS; CCDS33530.1; -. [P39086-2]
DR CCDS; CCDS42913.1; -. [P39086-1]
DR PIR; I58178; I58178.
DR RefSeq; NP_000821.1; NM_000830.4. [P39086-1]
DR RefSeq; NP_001307545.1; NM_001320616.1.
DR RefSeq; NP_001307547.1; NM_001320618.1.
DR RefSeq; NP_783300.1; NM_175611.2. [P39086-2]
DR PDB; 2ZNS; X-ray; 2.00 A; A=445-559, A=682-820.
DR PDB; 2ZNT; X-ray; 1.60 A; A=445-559, A=682-820.
DR PDB; 2ZNU; X-ray; 1.80 A; A=445-559, A=682-820.
DR PDB; 3FUZ; X-ray; 1.65 A; A/B=445-559, A/B=682-820.
DR PDB; 3FV1; X-ray; 1.50 A; A/B=445-559, A/B=682-820.
DR PDB; 3FV2; X-ray; 1.50 A; A/B=445-559, A/B=682-820.
DR PDB; 3FVG; X-ray; 1.50 A; A/B=445-559, A/B=682-820.
DR PDB; 3FVK; X-ray; 1.50 A; A/B=445-559, A/B=682-820.
DR PDB; 3FVN; X-ray; 1.50 A; A/B=445-559, A/B=682-820.
DR PDB; 3FVO; X-ray; 1.50 A; A/B=445-559, A/B=682-820.
DR PDB; 4MF3; X-ray; 3.00 A; A/B=443-559, A/B=682-822.
DR PDBsum; 2ZNS; -.
DR PDBsum; 2ZNT; -.
DR PDBsum; 2ZNU; -.
DR PDBsum; 3FUZ; -.
DR PDBsum; 3FV1; -.
DR PDBsum; 3FV2; -.
DR PDBsum; 3FVG; -.
DR PDBsum; 3FVK; -.
DR PDBsum; 3FVN; -.
DR PDBsum; 3FVO; -.
DR PDBsum; 4MF3; -.
DR AlphaFoldDB; P39086; -.
DR SMR; P39086; -.
DR BioGRID; 109154; 9.
DR IntAct; P39086; 2.
DR MINT; P39086; -.
DR STRING; 9606.ENSP00000382791; -.
DR BindingDB; P39086; -.
DR ChEMBL; CHEMBL1918; -.
DR DrugBank; DB00237; Butabarbital.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB06354; Tezampanel.
DR DrugBank; DB00273; Topiramate.
DR DrugCentral; P39086; -.
DR GuidetoPHARMACOLOGY; 450; -.
DR GlyGen; P39086; 9 sites.
DR iPTMnet; P39086; -.
DR PhosphoSitePlus; P39086; -.
DR BioMuta; GRIK1; -.
DR DMDM; 729597; -.
DR MassIVE; P39086; -.
DR PaxDb; P39086; -.
DR PeptideAtlas; P39086; -.
DR PRIDE; P39086; -.
DR ProteomicsDB; 55314; -. [P39086-1]
DR ProteomicsDB; 55315; -. [P39086-2]
DR Antibodypedia; 22450; 304 antibodies from 36 providers.
DR DNASU; 2897; -.
DR Ensembl; ENST00000389125.7; ENSP00000373777.3; ENSG00000171189.18. [P39086-2]
DR Ensembl; ENST00000399907.5; ENSP00000382791.1; ENSG00000171189.18. [P39086-1]
DR GeneID; 2897; -.
DR KEGG; hsa:2897; -.
DR UCSC; uc002ynn.4; human. [P39086-1]
DR CTD; 2897; -.
DR DisGeNET; 2897; -.
DR GeneCards; GRIK1; -.
DR HGNC; HGNC:4579; GRIK1.
DR HPA; ENSG00000171189; Group enriched (adrenal gland, brain, retina).
DR MIM; 138245; gene.
DR neXtProt; NX_P39086; -.
DR OpenTargets; ENSG00000171189; -.
DR PharmGKB; PA28973; -.
DR VEuPathDB; HostDB:ENSG00000171189; -.
DR eggNOG; KOG1052; Eukaryota.
DR GeneTree; ENSGT00940000156253; -.
DR HOGENOM; CLU_007257_1_2_1; -.
DR InParanoid; P39086; -.
DR OMA; TMDMELF; -.
DR PhylomeDB; P39086; -.
DR TreeFam; TF334668; -.
DR PathwayCommons; P39086; -.
DR Reactome; R-HSA-451307; Activation of Na-permeable kainate receptors.
DR Reactome; R-HSA-451308; Activation of Ca-permeable Kainate Receptor.
DR SignaLink; P39086; -.
DR SIGNOR; P39086; -.
DR BioGRID-ORCS; 2897; 17 hits in 1065 CRISPR screens.
DR ChiTaRS; GRIK1; human.
DR EvolutionaryTrace; P39086; -.
DR GeneWiki; GRIK1; -.
DR GenomeRNAi; 2897; -.
DR Pharos; P39086; Tclin.
DR PRO; PR:P39086; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P39086; protein.
DR Bgee; ENSG00000171189; Expressed in cingulate cortex and 133 other tissues.
DR ExpressionAtlas; P39086; baseline and differential.
DR Genevisible; P39086; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0008066; F:glutamate receptor activity; IBA:GO_Central.
DR GO; GO:0015277; F:kainate selective glutamate receptor activity; IDA: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; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0007215; P:glutamate receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; TAS:UniProtKB.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central.
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 3D-structure; Alternative splicing; Cell membrane; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW RNA editing; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..918
FT /note="Glutamate receptor ionotropic, kainate 1"
FT /id="PRO_0000011541"
FT TOPO_DOM 31..576
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 577..597
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 598..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..674
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 675..834
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 835..855
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 856..918
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 531..533
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 538
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 704..705
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 753
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT MOD_RES 725
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 761
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 428
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 561
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 766
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 402..416
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8589992, ECO:0000303|Ref.3"
FT /id="VSP_000127"
FT VAR_SEQ 870..918
FT /note="AFCFFYGLQCKQTHPTNSTSGTTLSTDLECGKLIREERGIRKQSSVHTV ->
FT CLSFNAIMEELGISLKNQKKIKKKSRTKGKSSFTSILTCHQRRTQRKETVA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:8589992, ECO:0000303|Ref.3"
FT /id="VSP_000128"
FT VARIANT 332
FT /note="A -> V (in dbSNP:rs143252117)"
FT /evidence="ECO:0000269|PubMed:11702055"
FT /id="VAR_012751"
FT VARIANT 636
FT /note="Q -> R (in RNA edited version)"
FT /id="VAR_000304"
FT VARIANT 757
FT /note="I -> V (in dbSNP:rs363494)"
FT /id="VAR_012041"
FT VARIANT 862
FT /note="R -> Q (in dbSNP:rs761410270)"
FT /evidence="ECO:0000269|PubMed:11702055"
FT /id="VAR_012752"
FT VARIANT 870
FT /note="A -> V (in dbSNP:rs363503)"
FT /id="VAR_012042"
FT VARIANT 902
FT /note="L -> S (in dbSNP:rs363504)"
FT /evidence="ECO:0000269|PubMed:11702055"
FT /id="VAR_012043"
FT CONFLICT 281
FT /note="R -> G (in Ref. 2; AAA95961)"
FT /evidence="ECO:0000305"
FT STRAND 449..453
FT /evidence="ECO:0007829|PDB:3FV1"
FT TURN 457..459
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 471..474
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 478..490
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 494..498
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 515..521
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 536..539
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 542..544
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 548..551
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 553..559
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 686..691
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 693..698
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 704..711
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 715..726
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 728..731
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 732..735
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 736..745
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 746..753
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 754..761
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 767..771
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 777..779
FT /evidence="ECO:0007829|PDB:3FV1"
FT STRAND 782..784
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 790..802
FT /evidence="ECO:0007829|PDB:3FV1"
FT HELIX 805..814
FT /evidence="ECO:0007829|PDB:3FV1"
SQ SEQUENCE 918 AA; 103981 MW; 0EB8DB6356599002 CRC64;
MEHGTLLAQP GLWTRDTSWA LLYFLCYILP QTAPQVLRIG GIFETVENEP VNVEELAFKF
AVTSINRNRT LMPNTTLTYD IQRINLFDSF EASRRACDQL ALGVAALFGP SHSSSVSAVQ
SICNALEVPH IQTRWKHPSV DNKDLFYINL YPDYAAISRA ILDLVLYYNW KTVTVVYEDS
TGLIRLQELI KAPSRYNIKI KIRQLPSGNK DAKPLLKEMK KGKEFYVIFD CSHETAAEIL
KQILFMGMMT EYYHYFFTTL DLFALDLELY RYSGVNMTGF RLLNIDNPHV SSIIEKWSME
RLQAPPRPET GLLDGMMTTE AALMYDAVYM VAIASHRASQ LTVSSLQCHR HKPWRLGPRF
MNLIKEARWD GLTGHITFNK TNGLRKDFDL DIISLKEEGT EKAAGEVSKH LYKVWKKIGI
WNSNSGLNMT DSNKDKSSNI TDSLANRTLI VTTILEEPYV MYRKSDKPLY GNDRFEGYCL
DLLKELSNIL GFIYDVKLVP DGKYGAQNDK GEWNGMVKEL IDHRADLAVA PLTITYVREK
VIDFSKPFMT LGISILYRKP NGTNPGVFSF LNPLSPDIWM YVLLACLGVS CVLFVIARFT
PYEWYNPHPC NPDSDVVENN FTLLNSFWFG VGALMQQGSE LMPKALSTRI VGGIWWFFTL
IIISSYTANL AAFLTVERME SPIDSADDLA KQTKIEYGAV RDGSTMTFFK KSKISTYEKM
WAFMSSRQQT ALVRNSDEGI QRVLTTDYAL LMESTSIEYV TQRNCNLTQI GGLIDSKGYG
VGTPIGSPYR DKITIAILQL QEEGKLHMMK EKWWRGNGCP EEDNKEASAL GVENIGGIFI
VLAAGLVLSV FVAIGEFIYK SRKNNDIEQA FCFFYGLQCK QTHPTNSTSG TTLSTDLECG
KLIREERGIR KQSSVHTV
