Reviewed, UniProtKB/Swiss-Prot P39086 (GRIK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Glutamate receptor, ionotropic kainate 1
Alternative name(s):
    Glutamate receptor 5
      Short name=GluR-5
      Short name=GluR5
    Excitatory amino acid receptor 3
      Short name=EAA3

Gene names

Name:	GRIK1
Synonyms:	GLUR5

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	918 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic 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) family. [View classification]
RNA editing	Edited at position 636. Partially edited. Ref.4

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing Polymorphism RNA editing
Domain	Signal Transmembrane
Molecular function	Ionic channel Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	central nervous system development Traceable author statement. Source: ProtInc glutamate signaling pathway Ref.1 Traceable author statement. Source: ProtInc ion transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of synaptic transmission, glutamatergic Traceable author statement. Source: UniProtKB synaptic transmission Traceable author statement. Source: ProtInc
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	extracellular-glutamate-gated ion channel activity Inferred from electronic annotation. Source: InterPro kainate selective glutamate receptor activity Inferred from direct assay. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Potential

Chain

31 – 918

888

Glutamate receptor, ionotropic kainate 1

PRO_0000011541

Regions

Topological domain

31 – 576

546

Extracellular Potential

Transmembrane

577 – 597

21

Potential

Topological domain

598 – 653

56

Cytoplasmic Potential

Transmembrane

654 – 674

21

Potential

Topological domain

675 – 834

160

Extracellular Potential

Transmembrane

835 – 855

21

Potential

Topological domain

856 – 918

63

Cytoplasmic Potential

Region

531 – 533

3

Glutamate binding By similarity

Region

704 – 705

2

Glutamate binding By similarity

Sites

Binding site

538

1

Glutamate By similarity

Binding site

753

1

Glutamate By similarity

Amino acid modifications

Modified residue

725

1

Phosphoserine; by PKC Potential

Modified residue

761

1

Phosphothreonine; by PKC Potential

Glycosylation

68

1

N-linked (GlcNAc...) Potential

Glycosylation

74

1

N-linked (GlcNAc...) Potential

Glycosylation

276

1

N-linked (GlcNAc...) Potential

Glycosylation

379

1

N-linked (GlcNAc...) Potential

Glycosylation

428

1

N-linked (GlcNAc...) Potential

Glycosylation

439

1

N-linked (GlcNAc...) Potential

Glycosylation

446

1

N-linked (GlcNAc...) Potential

Glycosylation

561

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

402 – 416

15

Missing in isoform 2.

VSP_000127

Alternative sequence

870 – 918

49

AFCFF…SVHTV → CLSFNAIMEELGISLKNQKK IKKKSRTKGKSSFTSILTCH QRRTQRKETVA in isoform 2.

VSP_000128

Natural variant

332

1

A → V

VAR_012751

Natural variant

636

1

Q → R in RNA edited version.

VAR_000304

Natural variant

757

1

I → V: dbSNP rs363494.

VAR_012041

Natural variant

862

1

R → Q

VAR_012752

Natural variant

870

1

A → V: dbSNP rs363503.

VAR_012042

Natural variant

902

1

L → S: dbSNP rs363504. Ref.5

VAR_012043

Experimental info

Sequence conflict

281

1

R → G in AAA95961. Ref.2

Secondary structure

1

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918

Helix Strand Turn

Details...

Beta strand

449 – 453

5

Turn

457 – 459

3

Beta strand

460 – 462

3

Helix

479 – 489

11

Beta strand

494 – 498

5

Helix

517 – 521

5

Beta strand

526 – 528

3

Helix

536 – 539

4

Beta strand

553 – 558

6

Helix

686 – 690

5

Beta strand

693 – 696

4

Helix

705 – 711

7

Helix

715 – 726

12

Helix

728 – 731

4

Beta strand

732 – 736

5

Helix

741 – 745

5

Beta strand

746 – 748

3

Beta strand

750 – 752

3

Helix

754 – 761

8

Beta strand

767 – 770

4

Beta strand

773 – 777

5

Helix

789 – 802

14

Helix

806 – 814

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (GluR5-1D) [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 0EB8DB6356599002	FASTA	918	103,981
	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
	Isoform 2 (EAA3A). Checksum: 6D9350206E5A2E9C	FASTA	905	102,631
	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 EKIGIWNSNS GLNMTDSNKD 430 440 450 460 470 480 KSSNITDSLA NRTLIVTTIL EEPYVMYRKS DKPLYGNDRF EGYCLDLLKE LSNILGFIYD 490 500 510 520 530 540 VKLVPDGKYG AQNDKGEWNG MVKELIDHRA DLAVAPLTIT YVREKVIDFS KPFMTLGISI 550 560 570 580 590 600 LYRKPNGTNP GVFSFLNPLS PDIWMYVLLA CLGVSCVLFV IARFTPYEWY NPHPCNPDSD 610 620 630 640 650 660 VVENNFTLLN SFWFGVGALM QQGSELMPKA LSTRIVGGIW WFFTLIIISS YTANLAAFLT 670 680 690 700 710 720 VERMESPIDS ADDLAKQTKI EYGAVRDGST MTFFKKSKIS TYEKMWAFMS SRQQTALVRN 730 740 750 760 770 780 SDEGIQRVLT TDYALLMEST SIEYVTQRNC NLTQIGGLID SKGYGVGTPI GSPYRDKITI 790 800 810 820 830 840 AILQLQEEGK LHMMKEKWWR GNGCPEEDNK EASALGVENI GGIFIVLAAG LVLSVFVAIG 850 860 870 880 890 900 EFIYKSRKNN DIEQCLSFNA IMEELGISLK NQKKIKKKSR TKGKSSFTSI LTCHQRRTQR KETVA

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: 8260617] [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: 8589992] [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: 7696618] [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: 11702055] [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.

IPI

IPI00783047.
IPI00937051.

PIR

I58178.

RefSeq

NP_000821.1.
NP_783300.1.

UniGene

Hs.706747

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZNS	X-ray	2.00	A	445-820	[»]
2ZNT	X-ray	1.60	A	445-820	[»]
2ZNU	X-ray	1.80	A	445-820	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P39086.

PTM databases

PhosphoSite

P39086.

Proteomic databases

PRIDE

P39086.

Genome annotation databases

Ensembl

ENST00000399907; ENSP00000382791; ENSG00000171189; Homo sapiens. [Genome view]

GeneID

2897.

KEGG

hsa:2897.

UCSC

uc002ynn.1. human.
uc002yno.1. human.

Organism-specific databases

CTD

2897.

GeneCards

GC21M029831.

H-InvDB

HIX0016052.

HGNC

HGNC:4579. GRIK1.

MIM

138245. gene.

PharmGKB

PA28973.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16741.

HOVERGEN

P39086.

PhylomeDB

P39086.

Gene expression databases

ArrayExpress

P39086.

Bgee

P39086.

CleanEx

HS_GRIK1.

Genevestigator

P39086.

GermOnline

ENSG00000171189. Homo sapiens.

Family and domain databases

InterPro

IPR001828. ANF_lig_bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR015683. Glutamate_receptor-rel.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
[Graphical view]

PANTHER

PTHR18966. Glut_Rec_Related. 1 hit.

Pfam

PF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]

PRINTS

PR00177. NMDARECEPTOR.

SMART

SM00079. PBPe. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00142. L-Glutamic Acid.
DB00273. Topiramate.

NextBio

11463.

SOURCE

Search...

Entry information

Entry name

GRIK1_HUMAN

Accession

Primary (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:	January 19, 2010
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.