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Reviewed, UniProtKB/Swiss-Prot P42262 (GRIA2_HUMAN)

Last modified January 19, 2010. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Glutamate receptor 2
      Short name=GluR-2
Alternative name(s):
    GluR-B
    GluR-K2
    Glutamate receptor ionotropic, AMPA 2
    AMPA-selective glutamate receptor 2
Gene names
Name: GRIA2
Synonyms: GLUR2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length883 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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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.

Subunit structure

Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. May interact with MPP4. Forms a ternary complex with GRIP1 and CSPG4. Interacts with PICK1 (via PDZ domain). Interacts with PRKCABP, GRIP1 and GRIP2 By similarity. Ref.5

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein.

Post-translational modification

Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-610 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-836 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis By similarity.

Miscellaneous

The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.

Sequence similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10) family. [View classification]

RNA editing

Edited at position 607.
Partially edited. Fully edited in the brain. Heteromerically expressed edited GLUR2 (R) receptor complexes are impermeable to calcium, whereas the unedited (Q) forms are highly permeable to divalent ions. Ref.3

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Flop (identifier: P42262-1)

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 Flip (identifier: P42262-2)

The sequence of this isoform differs from the canonical sequence as follows:
     765-766: NA → TP
     775-775: N → S
     779-779: L → V
     796-800: SGGGD → AKDSG
Isoform 3 (identifier: P42262-3)

Also known as: Long;

The sequence of this isoform differs from the canonical sequence as follows:
     848-883: VAKNAQNINP...NVYGIESVKI → MTLNDAMRNK...GMNVSVTDLS

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 883859Glutamate receptor 2
PRO_0000011532

Regions

Topological domain25 – 543519Extracellular Potential
Transmembrane544 – 56421 Potential
Topological domain565 – 62460Cytoplasmic Potential
Transmembrane625 – 64521 Potential
Topological domain646 – 812167Extracellular Potential
Transmembrane813 – 83321 Potential
Topological domain834 – 88350Cytoplasmic Potential
Region499 – 5013Glutamate binding By similarity
Region675 – 6762Glutamate binding By similarity

Sites

Binding site5061Glutamate By similarity
Binding site7261Glutamate By similarity

Amino acid modifications

Modified residue6831Phosphoserine; by PKC By similarity
Modified residue7171Phosphoserine; by PKG By similarity
Modified residue8691Phosphotyrosine By similarity
Modified residue8761Phosphotyrosine By similarity
Modified residue8801Phosphoserine By similarity
Lipidation6101S-palmitoyl cysteine By similarity
Lipidation8361S-palmitoyl cysteine By similarity
Glycosylation2561N-linked (GlcNAc...) Potential
Glycosylation3701N-linked (GlcNAc...) Potential
Glycosylation4061N-linked (GlcNAc...) Potential
Glycosylation4131N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence765 – 7662NA → TP in isoform Flip.
VSP_000102
Alternative sequence7751N → S in isoform Flip.
VSP_000103
Alternative sequence7791L → V in isoform Flip.
VSP_000104
Alternative sequence796 – 8005SGGGD → AKDSG in isoform Flip.
VSP_000105
Alternative sequence848 – 88336VAKNA…ESVKI → MTLNDAMRNKARLSITGSTG ENGRVMTPEFPKAVHAVPYV SPGMGMNVSVTDLS in isoform 3.
VSP_029309
Natural variant6071Q → R in RNA edited version. dbSNP rs17850674. Ref.1 Ref.2
VAR_000303
Natural variant6081Q → R: dbSNP rs17850675. Ref.2
VAR_037055

Experimental info

Sequence conflict1401I → V in AAH10574. Ref.2
Sequence conflict2411G → E in AAA58631. Ref.1
Sequence conflict7641R → G in AAA58631. Ref.1

Secondary structure

1 .................................................... 883
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform Flop [UniParc].

Last modified October 10, 2002. Version 3.
Checksum: 6DAB96C76D1D8448

FASTA88398,821
        10         20         30         40         50         60 
MQKIMHISVL LSPVLWGLIF GVSSNSIQIG GLFPRGADQE YSAFRVGMVQ FSTSEFRLTP 

        70         80         90        100        110        120 
HIDNLEVANS FAVTNAFCSQ FSRGVYAIFG FYDKKSVNTI TSFCGTLHVS FITPSFPTDG 

       130        140        150        160        170        180 
THPFVIQMRP DLKGALLSLI EYYQWDKFAY LYDSDRGLST LQAVLDSAAE KKWQVTAINV 

       190        200        210        220        230        240 
GNINNDKKDE MYRSLFQDLE LKKERRVILD CERDKVNDIV DQVITIGKHV KGYHYIIANL 

       250        260        270        280        290        300 
GFTDGDLLKI QFGGANVSGF QIVDYDDSLV SKFIERWSTL EEKEYPGAHT TTIKYTSALT 

       310        320        330        340        350        360 
YDAVQVMTEA FRNLRKQRIE ISRRGNAGDC LANPAVPWGQ GVEIERALKQ VQVEGLSGNI 

       370        380        390        400        410        420 
KFDQNGKRIN YTINIMELKT NGPRKIGYWS EVDKMVVTLT ELPSGNDTSG LENKTVVVTT 

       430        440        450        460        470        480 
ILESPYVMMK KNHEMLEGNE RYEGYCVDLA AEIAKHCGFK YKLTIVGDGK YGARDADTKI 

       490        500        510        520        530        540 
WNGMVGELVY GKADIAIAPL TITLVREEVI DFSKPFMSLG ISIMIKKPQK SKPGVFSFLD 

       550        560        570        580        590        600 
PLAYEIWMCI VFAYIGVSVV LFLVSRFSPY EWHTEEFEDG RETQSSESTN EFGIFNSLWF 

       610        620        630        640        650        660 
SLGAFMQQGC DISPRSLSGR IVGGVWWFFT LIIISSYTAN LAAFLTVERM VSPIESAEDL 

       670        680        690        700        710        720 
SKQTEIAYGT LDSGSTKEFF RRSKIAVFDK MWTYMRSAEP SVFVRTTAEG VARVRKSKGK 

       730        740        750        760        770        780 
YAYLLESTMN EYIEQRKPCD TMKVGGNLDS KGYGIATPKG SSLRNAVNLA VLKLNEQGLL 

       790        800        810        820        830        840 
DKLKNKWWYD KGECGSGGGD SKEKTSALSL SNVAGVFYIL VGGLGLAMLV ALIEFCYKSR 

       850        860        870        880 
AEAKRMKVAK NAQNINPSSS QNSQNFATYK EGYNVYGIES VKI

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Isoform Flip.

Checksum: 882141AC054254F8
Show »

FASTA88398,878
Isoform 3 (Long).

Checksum: 6E668073D621EFBB
Show »

FASTA901100,594

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References

« Hide 'large scale' references
[1]"Primary structure and functional expression of the AMPA/kainate receptor subunit 2 from human brain."
Sun W., Ferrer-Montiel A.V., Montal M.
NeuroReport 5:441-444(1994) [PubMed: 8003671] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FLIP), VARIANT ARG-607.
Tissue: Brain.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM FLOP), VARIANTS ARG-607 AND ARG-608.
Tissue: Brain.
[3]"RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue."
Paschen W., Hedreen J.C., Ross C.A.
J. Neurochem. 63:1596-1602(1994) [PubMed: 7523595] [Abstract]
Cited for: RNA EDITING OF POSITION 607.
[4]"Glutamatergic plasticity by synaptic delivery of GluR-B(long)-containing AMPA receptors."
Kolleker A., Zhu J.J., Schupp B.J., Qin Y., Mack V., Borchardt T., Koehr G., Malinow R., Seeburg P.H., Osten P.
Neuron 40:1199-1212(2003) [PubMed: 14687553] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 3).
[5]"The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands."
Dev K.K., Nakanishi S., Henley J.M.
J. Biol. Chem. 279:41393-41397(2004) [PubMed: 15247289] [Abstract]
Cited for: INTERACTION WITH PICK1.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		L20814 mRNA. Translation: AAA58631.1.
BC010574 mRNA. Translation: AAH10574.1.
IPIIPI00030882.
IPI00219216.
IPI00871510.
PIRI58181.
RefSeqNP_000817.2.
NP_001077088.1.
NP_001077089.1.
UniGeneHs.32763

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WJWX-ray1.80A25-412[»]
2WJXX-ray4.10A/B/C25-412[»]
SMRP42262. Positions 396-796.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-42852N.
STRINGP42262.

PTM databases

PhosphoSiteP42262.

Proteomic databases

PRIDEP42262.

Genome annotation databases

EnsemblENST00000264426; ENSP00000264426; ENSG00000120251; Homo sapiens. [Genome view]
GeneID2891.
KEGGhsa:2891.
UCSCuc003ipm.2. human.

Organism-specific databases

CTD2891.
GeneCardsGC04P158361.
HGNCHGNC:4572. GRIA2.
HPACAB007812.
HPA008441.
MIM138247. gene.
PharmGKBPA28967.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14111.
HOVERGENP42262.
OMAADSKIRY.
OrthoDBEOG9RFPBS.

Enzyme and pathway databases

ReactomeREACT_13685. Synaptic Transmission.

Gene expression databases

ArrayExpressP42262.
BgeeP42262.
CleanExHS_GRIA2.
GenevestigatorP42262.
GermOnlineENSG00000120251. Homo sapiens.

Family and domain databases

InterProIPR001828. ANF_lig_bd_rcpt.
IPR019594. Glu_rcpt_Glu/Gly-bd.
IPR015683. Glutamate_receptor-rel.
IPR001320. Iontro_glu_rcpt.
IPR001508. NMDA_rcpt.
[Graphical view]
PANTHERPTHR18966. Glut_Rec_Related. 1 hit.
PfamPF01094. ANF_receptor. 1 hit.
PF00060. Lig_chan. 1 hit.
PF10613. Lig_chan-Glu_bd. 1 hit.
[Graphical view]
PRINTSPR00177. NMDARECEPTOR.
SMARTSM00079. PBPe. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00142. L-Glutamic Acid.
NextBio11429.
SOURCESearch...

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Entry information

Entry nameGRIA2_HUMAN
AccessionPrimary (citable) accession number: P42262
Secondary accession number(s): Q96FP6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 10, 2002
Last modified: January 19, 2010
This is version 107 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents