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P39086 (GRIK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glutamate receptor ionotropic, kainate 1

Short name=GluK1
Alternative name(s):
Excitatory amino acid receptor 3
Short name=EAA3
Glutamate receptor 5
Short name=GluR-5
Short name=GluR5
Gene names
Name:GRIK1
Synonyms:GLUR5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length918 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.

Subunit structure

Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers Probable. The unedited version (Q) assembles into a functional kainate-gated homomeric channel, whereas the edited version (R) is unable to produce channel activity when expressed alone. Both edited and unedited versions can form functional channels with GRIK4 and GRIK5. Interacts with KLHL17 By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein.

Tissue specificity

Most abundant in the cerebellum and the suprachiasmatic nuclei (SCN) of the hypothalamus.

Miscellaneous

The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate > L-glutamate = quisqualate > CNQX = DNQX > AMPA > dihydrokainate > NMDA.

Sequence similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK1 subfamily. [View classification]

RNA editing

Edited at position 636.
Partially edited. Ref.4

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
RNA editing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionIon channel
Ligand-gated ion channel
Receptor
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult behavior

Inferred from electronic annotation. Source: Ensembl

behavioral response to pain

Inferred from electronic annotation. Source: Ensembl

central nervous system development

Traceable author statement PubMed 10580501. Source: ProtInc

glutamate receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

ion transmembrane transport

Inferred from Biological aspect of Ancestor. Source: GOC

ionotropic glutamate receptor signaling pathway

Inferred from direct assay PubMed 9335499. Source: GOC

negative regulation of synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

nervous system development

Traceable author statement Ref.1. Source: ProtInc

positive regulation of gamma-aminobutyric acid secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of synaptic transmission, GABAergic

Inferred from electronic annotation. Source: Ensembl

regulation of excitatory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of inhibitory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic transmission, glutamatergic

Traceable author statement PubMed 9335499. Source: UniProtKB

synaptic transmission

Traceable author statement. Source: Reactome

synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

kainate selective glutamate receptor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

presynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionextracellular-glutamate-gated ion channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

kainate selective glutamate receptor activity

Inferred from direct assay PubMed 9335499. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P39086-1)

Also known as: GluR5-1D;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P39086-2)

Also known as: EAA3A;

The sequence of this isoform differs from the canonical sequence as follows:
     402-416: Missing.
     870-918: AFCFFYGLQC...IRKQSSVHTV → CLSFNAIMEE...RRTQRKETVA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Chain31 – 918888Glutamate receptor ionotropic, kainate 1
PRO_0000011541

Regions

Topological domain31 – 576546Extracellular Potential
Transmembrane577 – 59721Helical; Potential
Topological domain598 – 65356Cytoplasmic Potential
Transmembrane654 – 67421Helical; Potential
Topological domain675 – 834160Extracellular Potential
Transmembrane835 – 85521Helical; Potential
Topological domain856 – 91863Cytoplasmic Potential
Region531 – 5333Glutamate binding By similarity
Region704 – 7052Glutamate binding By similarity

Sites

Binding site5381Glutamate By similarity
Binding site7531Glutamate By similarity

Amino acid modifications

Modified residue7251Phosphoserine; by PKC Potential
Modified residue7611Phosphothreonine; by PKC Potential
Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation2761N-linked (GlcNAc...) Potential
Glycosylation3791N-linked (GlcNAc...) Potential
Glycosylation4281N-linked (GlcNAc...) Potential
Glycosylation4391N-linked (GlcNAc...) Potential
Glycosylation4461N-linked (GlcNAc...) Potential
Glycosylation5611N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence402 – 41615Missing in isoform 2.
VSP_000127
Alternative sequence870 – 91849AFCFF…SVHTV → CLSFNAIMEELGISLKNQKK IKKKSRTKGKSSFTSILTCH QRRTQRKETVA in isoform 2.
VSP_000128
Natural variant3321A → V. Ref.5
Corresponds to variant rs143252117 [ dbSNP | Ensembl ].
VAR_012751
Natural variant6361Q → R in RNA edited version.
VAR_000304
Natural variant7571I → V.
Corresponds to variant rs363494 [ dbSNP | Ensembl ].
VAR_012041
Natural variant8621R → Q. Ref.5
VAR_012752
Natural variant8701A → V.
Corresponds to variant rs363503 [ dbSNP | Ensembl ].
VAR_012042
Natural variant9021L → S. Ref.5
Corresponds to variant rs363504 [ dbSNP | Ensembl ].
VAR_012043

Experimental info

Sequence conflict2811R → G in AAA95961. Ref.2

Secondary structure

................................................ 918
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (GluR5-1D) [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 0EB8DB6356599002

FASTA918103,981
        10         20         30         40         50         60 
MEHGTLLAQP GLWTRDTSWA LLYFLCYILP QTAPQVLRIG GIFETVENEP VNVEELAFKF 

        70         80         90        100        110        120 
AVTSINRNRT LMPNTTLTYD IQRINLFDSF EASRRACDQL ALGVAALFGP SHSSSVSAVQ 

       130        140        150        160        170        180 
SICNALEVPH IQTRWKHPSV DNKDLFYINL YPDYAAISRA ILDLVLYYNW KTVTVVYEDS 

       190        200        210        220        230        240 
TGLIRLQELI KAPSRYNIKI KIRQLPSGNK DAKPLLKEMK KGKEFYVIFD CSHETAAEIL 

       250        260        270        280        290        300 
KQILFMGMMT EYYHYFFTTL DLFALDLELY RYSGVNMTGF RLLNIDNPHV SSIIEKWSME 

       310        320        330        340        350        360 
RLQAPPRPET GLLDGMMTTE AALMYDAVYM VAIASHRASQ LTVSSLQCHR HKPWRLGPRF 

       370        380        390        400        410        420 
MNLIKEARWD GLTGHITFNK TNGLRKDFDL DIISLKEEGT EKAAGEVSKH LYKVWKKIGI 

       430        440        450        460        470        480 
WNSNSGLNMT DSNKDKSSNI TDSLANRTLI VTTILEEPYV MYRKSDKPLY GNDRFEGYCL 

       490        500        510        520        530        540 
DLLKELSNIL GFIYDVKLVP DGKYGAQNDK GEWNGMVKEL IDHRADLAVA PLTITYVREK 

       550        560        570        580        590        600 
VIDFSKPFMT LGISILYRKP NGTNPGVFSF LNPLSPDIWM YVLLACLGVS CVLFVIARFT 

       610        620        630        640        650        660 
PYEWYNPHPC NPDSDVVENN FTLLNSFWFG VGALMQQGSE LMPKALSTRI VGGIWWFFTL 

       670        680        690        700        710        720 
IIISSYTANL AAFLTVERME SPIDSADDLA KQTKIEYGAV RDGSTMTFFK KSKISTYEKM 

       730        740        750        760        770        780 
WAFMSSRQQT ALVRNSDEGI QRVLTTDYAL LMESTSIEYV TQRNCNLTQI GGLIDSKGYG 

       790        800        810        820        830        840 
VGTPIGSPYR DKITIAILQL QEEGKLHMMK EKWWRGNGCP EEDNKEASAL GVENIGGIFI 

       850        860        870        880        890        900 
VLAAGLVLSV FVAIGEFIYK SRKNNDIEQA FCFFYGLQCK QTHPTNSTSG TTLSTDLECG 

       910 
KLIREERGIR KQSSVHTV 

« Hide

Isoform 2 (EAA3A) [UniParc].

Checksum: 6D9350206E5A2E9C
Show »

FASTA905102,631

References

[1]"Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6."
Gregor P., O'Hara B.F., Yang X., Uhl G.R.
NeuroReport 4:1343-1346(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Retina.
[2]"cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration."
Korczak B., Nutt S.L., Fletcher E.J., Hoo K.H., Elliott C.E., Rampersad V., McWhinnie E.A., Kamboj R.K.
Recept. Channels 3:41-49(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Fetal brain.
[3]"Myeloid progenitor cell growth and apoptosis involves known and cell-specific ionotropic glutamate receptors."
Langer A., Xu D., Kuehcke K., Fehse B., Abdallah S., Lother H.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Erythroleukemia.
[4]"RNA editing of human kainate receptor subunits."
Nutt S.L., Kamboj R.K.
NeuroReport 5:2625-2629(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: RNA EDITING OF POSITION 636.
Tissue: Brain.
[5]"Association study of polymorphisms in the GluR5 kainate receptor gene (GRIK1) with schizophrenia."
Shibata H., Joo A., Fujii Y., Tani A., Makino C., Hirata N., Kikuta R., Ninomiya H., Tashiro N., Fukumaki Y.
Psychiatr. Genet. 11:139-144(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-332; GLN-862 AND SER-902.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L19058 mRNA. Translation: AAA52568.1.
U16125 mRNA. Translation: AAA95961.1.
AJ249208 mRNA. Translation: CAC80546.1.
PIRI58178.
RefSeqNP_000821.1. NM_000830.3.
NP_783300.1. NM_175611.2.
UniGeneHs.664641.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZNSX-ray2.00A445-820[»]
2ZNTX-ray1.60A445-820[»]
2ZNUX-ray1.80A445-820[»]
3FUZX-ray1.65A/B445-820[»]
3FV1X-ray1.50A/B445-820[»]
3FV2X-ray1.50A/B445-820[»]
3FVGX-ray1.50A/B445-820[»]
3FVKX-ray1.50A/B445-820[»]
3FVNX-ray1.50A/B445-820[»]
3FVOX-ray1.50A/B445-820[»]
ProteinModelPortalP39086.
SMRP39086. Positions 35-860.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109154. 6 interactions.
STRING9606.ENSP00000382791.

Chemistry

BindingDBP39086.
ChEMBLCHEMBL2109241.
DrugBankDB00142. L-Glutamic Acid.
DB00273. Topiramate.
GuidetoPHARMACOLOGY450.

PTM databases

PhosphoSiteP39086.

Polymorphism databases

DMDM729597.

Proteomic databases

PaxDbP39086.
PRIDEP39086.

Protocols and materials databases

DNASU2897.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000389125; ENSP00000373777; ENSG00000171189. [P39086-2]
ENST00000399907; ENSP00000382791; ENSG00000171189. [P39086-1]
GeneID2897.
KEGGhsa:2897.
UCSCuc002ynn.3. human. [P39086-2]
uc002yno.1. human. [P39086-1]

Organism-specific databases

CTD2897.
GeneCardsGC21M030909.
HGNCHGNC:4579. GRIK1.
MIM138245. gene.
neXtProtNX_P39086.
PharmGKBPA28973.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG316680.
HOGENOMHOG000234371.
HOVERGENHBG051839.
KOK05201.
PhylomeDBP39086.
TreeFamTF334668.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
SignaLinkP39086.

Gene expression databases

ArrayExpressP39086.
BgeeP39086.
CleanExHS_GRIK1.
GenevestigatorP39086.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSPR00177. NMDARECEPTOR.
SMARTSM00918. Lig_chan-Glu_bd. 1 hit.
SM00079. PBPe. 1 hit.
[Graphical view]
SUPFAMSSF53822. SSF53822. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP39086.
GeneWikiGRIK1.
GenomeRNAi2897.
NextBio11463.
PROP39086.
SOURCESearch...

Entry information

Entry nameGRIK1_HUMAN
AccessionPrimary (citable) accession number: P39086
Secondary accession number(s): Q13001, Q86SU9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM