GRIK3_HUMAN
ID GRIK3_HUMAN Reviewed; 919 AA.
AC Q13003; A9Z1Z8; B1AMS6; Q13004; Q16136;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Glutamate receptor ionotropic, kainate 3;
DE Short=GluK3;
DE AltName: Full=Excitatory amino acid receptor 5;
DE Short=EAA5;
DE AltName: Full=Glutamate receptor 7;
DE Short=GluR-7;
DE Short=GluR7;
DE Flags: Precursor;
GN Name=GRIK3; Synonyms=GLUR7;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT ALA-310, AND
RP RNA EDITING OF POSITION 352.
RC TISSUE=Fetal brain;
RX PubMed=7719709;
RA Nutt S.L., Hoo K.H., Rampersad V., Deverill R.M., Elliott C.E.,
RA Fletcher E.J., Adams S.-L., Korczak B., Foldes R.L., Kamboj R.K.;
RT "Molecular characterization of the human EAA5 (GluR7) receptor: a high-
RT affinity kainate receptor with novel potential RNA editing sites.";
RL Recept. Channels 2:315-326(1994).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 268-320.
RC TISSUE=Placenta;
RX PubMed=8128318; DOI=10.1007/bf01233385;
RA Puranam R.S., Eubanks J.H., Heinemann S.F., McNamara J.O.;
RT "Chromosomal localization of gene for human glutamate receptor subunit-7.";
RL Somat. Cell Mol. Genet. 19:581-588(1993).
RN [6]
RP VARIANT ALA-310.
RX PubMed=11124978; DOI=10.1523/jneurosci.20-24-09025.2000;
RA Schiffer H.H., Swanson G.T., Masliah E., Heinemann S.F.;
RT "Unequal expression of allelic kainate receptor GluR7 mRNAs in human
RT brains.";
RL J. Neurosci. 20:9025-9033(2000).
RN [7]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-215 AND HIS-391.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
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. The
CC postsynaptic actions of Glu are mediated by a variety of receptors that
CC are named according to their selective agonists. This receptor binds
CC domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.
CC -!- SUBUNIT: Homotetramer, and heterotetramer with either GRIK4 or GRIK5.
CC Interacts with PRKCABP (By similarity). Interacts with NETO2 (By
CC similarity). {ECO:0000250}.
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 Name=1;
CC IsoId=Q13003-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13003-2; Sequence=VSP_056588;
CC -!- RNA EDITING: Modified_positions=352 {ECO:0000269|PubMed:7719709};
CC Note=Partially edited.;
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. GRIK3 subfamily. {ECO:0000305}.
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DR EMBL; U16127; AAB60407.1; -; mRNA.
DR EMBL; U16128; AAC50421.1; -; Genomic_DNA.
DR EMBL; AJ249210; CAC80548.1; -; mRNA.
DR EMBL; AC117945; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355386; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07350.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07351.1; -; Genomic_DNA.
DR EMBL; S69349; AAB30157.1; -; Genomic_DNA.
DR CCDS; CCDS416.1; -. [Q13003-1]
DR PIR; I59604; I59604.
DR RefSeq; NP_000822.2; NM_000831.3. [Q13003-1]
DR AlphaFoldDB; Q13003; -.
DR SMR; Q13003; -.
DR BioGRID; 109156; 3.
DR IntAct; Q13003; 2.
DR STRING; 9606.ENSP00000362183; -.
DR BindingDB; Q13003; -.
DR ChEMBL; CHEMBL3684; -.
DR DrugBank; DB00237; Butabarbital.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB00273; Topiramate.
DR DrugCentral; Q13003; -.
DR GuidetoPHARMACOLOGY; 452; -.
DR GlyGen; Q13003; 10 sites.
DR iPTMnet; Q13003; -.
DR PhosphoSitePlus; Q13003; -.
DR BioMuta; GRIK3; -.
DR DMDM; 212276502; -.
DR EPD; Q13003; -.
DR jPOST; Q13003; -.
DR MassIVE; Q13003; -.
DR PaxDb; Q13003; -.
DR PeptideAtlas; Q13003; -.
DR PRIDE; Q13003; -.
DR ProteomicsDB; 2530; -.
DR ProteomicsDB; 59094; -. [Q13003-1]
DR Antibodypedia; 3095; 187 antibodies from 28 providers.
DR DNASU; 2899; -.
DR Ensembl; ENST00000373091.8; ENSP00000362183.3; ENSG00000163873.10. [Q13003-1]
DR Ensembl; ENST00000373093.4; ENSP00000362185.4; ENSG00000163873.10. [Q13003-2]
DR GeneID; 2899; -.
DR KEGG; hsa:2899; -.
DR MANE-Select; ENST00000373091.8; ENSP00000362183.3; NM_000831.4; NP_000822.2.
DR UCSC; uc001caz.3; human. [Q13003-1]
DR CTD; 2899; -.
DR DisGeNET; 2899; -.
DR GeneCards; GRIK3; -.
DR HGNC; HGNC:4581; GRIK3.
DR HPA; ENSG00000163873; Tissue enhanced (brain, pituitary gland).
DR MIM; 138243; gene.
DR neXtProt; NX_Q13003; -.
DR OpenTargets; ENSG00000163873; -.
DR PharmGKB; PA28975; -.
DR VEuPathDB; HostDB:ENSG00000163873; -.
DR eggNOG; KOG1052; Eukaryota.
DR GeneTree; ENSGT00940000159465; -.
DR HOGENOM; CLU_007257_1_1_1; -.
DR InParanoid; Q13003; -.
DR OMA; EREQVFV; -.
DR OrthoDB; 188544at2759; -.
DR PhylomeDB; Q13003; -.
DR TreeFam; TF334668; -.
DR PathwayCommons; Q13003; -.
DR Reactome; R-HSA-451308; Activation of Ca-permeable Kainate Receptor.
DR Reactome; R-HSA-500657; Presynaptic function of Kainate receptors.
DR SignaLink; Q13003; -.
DR SIGNOR; Q13003; -.
DR BioGRID-ORCS; 2899; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; GRIK3; human.
DR GeneWiki; GRIK3; -.
DR GenomeRNAi; 2899; -.
DR Pharos; Q13003; Tclin.
DR PRO; PR:Q13003; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q13003; protein.
DR Bgee; ENSG00000163873; Expressed in cortical plate and 120 other tissues.
DR Genevisible; Q13003; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0032839; C:dendrite cytoplasm; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0032983; C:kainate selective glutamate receptor complex; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; ISS:UniProtKB.
DR GO; GO:0001640; F:adenylate cyclase inhibiting G protein-coupled glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0008066; F:glutamate receptor activity; IBA:GO_Central.
DR GO; GO:0004970; F:ionotropic glutamate receptor activity; IDA:MGI.
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:0099507; F:ligand-gated ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl.
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:0007216; P:G protein-coupled glutamate receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007215; P:glutamate receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; ISS:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:MGI.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Isopeptide bond; Ligand-gated ion channel;
KW Membrane; Phosphoprotein; Postsynaptic cell membrane; Receptor;
KW Reference proteome; RNA editing; Signal; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..919
FT /note="Glutamate receptor ionotropic, kainate 3"
FT /id="PRO_0000011547"
FT TOPO_DOM 32..563
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 564..584
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 585..636
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 637..657
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 658..820
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 821..841
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 842..919
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 520
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 525
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 690..692
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 739
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT MOD_RES 869
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13002"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 415
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 548
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 752
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 99..350
FT /evidence="ECO:0000250"
FT CROSSLNK 887
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:Q13002"
FT VAR_SEQ 856..919
FT /note="RSFCSTVADEIRFSLTCQRRVKHKPQPPMMVKTDAVINMHTFNDRRLPGKDS
FT MACSTSLAPVFP -> VSLRAWSLHRMGNGDSR (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_056588"
FT VARIANT 215
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs755366301)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035695"
FT VARIANT 310
FT /note="S -> A (in dbSNP:rs6691840)"
FT /evidence="ECO:0000269|PubMed:11124978,
FT ECO:0000269|PubMed:7719709"
FT /id="VAR_000308"
FT VARIANT 352
FT /note="R -> Q (in RNA edited version)"
FT /id="VAR_000309"
FT VARIANT 391
FT /note="D -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035696"
FT CONFLICT 303
FT /note="R -> L (in Ref. 3; AAB30157)"
FT /evidence="ECO:0000305"
FT CONFLICT 627
FT /note="E -> V (in Ref. 1; AAB60407)"
FT /evidence="ECO:0000305"
FT CONFLICT 713
FT /note="S -> R (in Ref. 1; AAB60407)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 919 AA; 104037 MW; 0F68F6CF33E4CE71 CRC64;
MTAPWRRLRS LVWEYWAGLL VCAFWIPDSR GMPHVIRIGG IFEYADGPNA QVMNAEEHAF
RFSANIINRN RTLLPNTTLT YDIQRIHFHD SFEATKKACD QLALGVVAIF GPSQGSCTNA
VQSICNALEV PHIQLRWKHH PLDNKDTFYV NLYPDYASLS HAILDLVQYL KWRSATVVYD
DSTGLIRLQE LIMAPSRYNI RLKIRQLPID SDDSRPLLKE MKRGREFRII FDCSHTMAAQ
ILKQAMAMGM MTEYYHFIFT TLDLYALDLE PYRYSGVNLT GFRILNVDNP HVSAIVEKWS
MERLQAAPRS ESGLLDGVMM TDAALLYDAV HIVSVCYQRA PQMTVNSLQC HRHKAWRFGG
RFMNFIKEAQ WEGLTGRIVF NKTSGLRTDF DLDIISLKED GLEKVGVWSP ADGLNITEVA
KGRGPNVTDS LTNRSLIVTT VLEEPFVMFR KSDRTLYGND RFEGYCIDLL KELAHILGFS
YEIRLVEDGK YGAQDDKGQW NGMVKELIDH KADLAVAPLT ITHVREKAID FSKPFMTLGV
SILYRKPNGT NPSVFSFLNP LSPDIWMYVL LAYLGVSCVL FVIARFSPYE WYDAHPCNPG
SEVVENNFTL LNSFWFGMGS LMQQGSELMP KALSTRIIGG IWWFFTLIII SSYTANLAAF
LTVERMESPI DSADDLAKQT KIEYGAVKDG ATMTFFKKSK ISTFEKMWAF MSSKPSALVK
NNEEGIQRAL TADYALLMES TTIEYVTQRN CNLTQIGGLI DSKGYGIGTP MGSPYRDKIT
IAILQLQEED KLHIMKEKWW RGSGCPEEEN KEASALGIQK IGGIFIVLAA GLVLSVLVAV
GEFVYKLRKT AEREQRSFCS TVADEIRFSL TCQRRVKHKP QPPMMVKTDA VINMHTFNDR
RLPGKDSMAC STSLAPVFP