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Q14416 (GRM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metabotropic glutamate receptor 2

Short name=mGluR2
Gene names
Name:GRM2
Synonyms:GPRC1B, MGLUR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length872 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization. Ref.1 Ref.7 Ref.8 Ref.9

Subunit structure

Interacts with GRASP By similarity. Interacts with HTR2A. Ref.7 Ref.8 Ref.9

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapse By similarity. Cell projectiondendrite By similarity Ref.7 Ref.8 Ref.9.

Tissue specificity

Detected in brain cortex (at protein level). Widely expressed in different regions of the adult brain as well as in fetal brain. Ref.7

Sequence similarities

Belongs to the G-protein coupled receptor 3 family.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
Synapse
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

glutamate secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of adenylate cyclase activity

Traceable author statement Ref.1. Source: ProtInc

regulation of synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

synaptic transmission

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendrite

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

intracellular

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

presynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionG-protein coupled receptor activity

Traceable author statement Ref.1. Source: UniProtKB

calcium channel regulator activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

glutamate receptor activity

Traceable author statement Ref.1. Source: UniProtKB

group II metabotropic glutamate receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 872854Metabotropic glutamate receptor 2
PRO_0000012925

Regions

Topological domain19 – 567549Extracellular Potential
Transmembrane568 – 59023Helical; Name=1; Potential
Topological domain591 – 60414Cytoplasmic Potential
Transmembrane605 – 62521Helical; Name=2; Potential
Topological domain626 – 63611Extracellular Potential
Transmembrane637 – 65519Helical; Name=3; Potential
Topological domain656 – 67924Cytoplasmic Potential
Transmembrane680 – 70021Helical; Name=4; Potential
Topological domain701 – 72525Extracellular Potential
Transmembrane726 – 74722Helical; Name=5; Potential
Topological domain748 – 76013Cytoplasmic Potential
Transmembrane761 – 78323Helical; Name=6; Potential
Topological domain784 – 79310Extracellular Potential
Transmembrane794 – 81926Helical; Name=7; Potential
Topological domain820 – 87253Cytoplasmic Potential
Region166 – 1683Glutamate binding By similarity
Region677 – 6859Important for interaction with HTR2A

Sites

Binding site1451Glutamate By similarity
Binding site2161Glutamate By similarity
Binding site2951Glutamate By similarity
Binding site3771Glutamate By similarity

Amino acid modifications

Glycosylation2031N-linked (GlcNAc...) Potential
Glycosylation2861N-linked (GlcNAc...) Potential
Glycosylation3381N-linked (GlcNAc...) Potential
Glycosylation4021N-linked (GlcNAc...) Potential
Glycosylation5471N-linked (GlcNAc...) Potential
Disulfide bond50 ↔ 92 By similarity
Disulfide bond234 ↔ 518 By similarity
Disulfide bond355 ↔ 362 By similarity
Disulfide bond400 ↔ 407 By similarity
Disulfide bond500 ↔ 519 By similarity
Disulfide bond504 ↔ 522 By similarity
Disulfide bond525 ↔ 537 By similarity
Disulfide bond540 ↔ 553 By similarity

Experimental info

Mutagenesis6771A → S: Impairs interaction with HTR2A. Ref.8
Mutagenesis6811A → F: Impairs interaction with HTR2A. Ref.8
Mutagenesis6851A → G: Impairs interaction with HTR2A. Ref.8
Sequence conflict121L → P in AAA76855. Ref.1
Sequence conflict2101V → E in AAA76855. Ref.1
Sequence conflict4961P → A in AAA76855. Ref.1
Sequence conflict7481K → N in AAA76855. Ref.1
Sequence conflict7761F → L in AAA76855. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q14416 [UniParc].

Last modified September 27, 2005. Version 2.
Checksum: 801976D034AA8100

FASTA87295,568
        10         20         30         40         50         60 
MGSLLALLAL LLLWGAVAEG PAKKVLTLEG DLVLGGLFPV HQKGGPAEDC GPVNEHRGIQ 

        70         80         90        100        110        120 
RLEAMLFALD RINRDPHLLP GVRLGAHILD SCSKDTHALE QALDFVRASL SRGADGSRHI 

       130        140        150        160        170        180 
CPDGSYATHG DAPTAITGVI GGSYSDVSIQ VANLLRLFQI PQISYASTSA KLSDKSRYDY 

       190        200        210        220        230        240 
FARTVPPDFF QAKAMAEILR FFNWTYVSTV ASEGDYGETG IEAFELEARA RNICVATSEK 

       250        260        270        280        290        300 
VGRAMSRAAF EGVVRALLQK PSARVAVLFT RSEDARELLA ASQRLNASFT WVASDGWGAL 

       310        320        330        340        350        360 
ESVVAGSEGA AEGAITIELA SYPISDFASY FQSLDPWNNS RNPWFREFWE QRFRCSFRQR 

       370        380        390        400        410        420 
DCAAHSLRAV PFEQESKIMF VVNAVYAMAH ALHNMHRALC PNTTRLCDAM RPVNGRRLYK 

       430        440        450        460        470        480 
DFVLNVKFDA PFRPADTHNE VRFDRFGDGI GRYNIFTYLR AGSGRYRYQK VGYWAEGLTL 

       490        500        510        520        530        540 
DTSLIPWASP SAGPLPASRC SEPCLQNEVK SVQPGEVCCW LCIPCQPYEY RLDEFTCADC 

       550        560        570        580        590        600 
GLGYWPNASL TGCFELPQEY IRWGDAWAVG PVTIACLGAL ATLFVLGVFV RHNATPVVKA 

       610        620        630        640        650        660 
SGRELCYILL GGVFLCYCMT FIFIAKPSTA VCTLRRLGLG TAFSVCYSAL LTKTNRIARI 

       670        680        690        700        710        720 
FGGAREGAQR PRFISPASQV AICLALISGQ LLIVVAWLVV EAPGTGKETA PERREVVTLR 

       730        740        750        760        770        780 
CNHRDASMLG SLAYNVLLIA LCTLYAFKTR KCPENFNEAK FIGFTMYTTC IIWLAFLPIF 

       790        800        810        820        830        840 
YVTSSDYRVQ TTTMCVSVSL SGSVVLGCLF APKLHIILFQ PQKNVVSHRA PTSRFGSAAA 

       850        860        870 
RASSSLGQGS GSQFVPTVCN GREVVDSTTS SL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2."
Flor P.J., Lindauer K., Puttner I., Ruegg D., Lukic S., Knopfel T., Kuhn R.
Eur. J. Neurosci. 7:622-629(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[2]"Structure and polymorphisms of the human metabotropic glutamate receptor type 2 (hmGluR2) gene: analysis of association with schizophrenia."
Yasuyuki F., Akiko J.
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Complete coding sequence of human metabotropic glutamate receptor 2."
Bonner T.I., Kauffman D., Nagle J.W.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[4]Kaighin V.A., Martin A.L., Aronstam R.S.
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain cortex.
[7]"Identification of a serotonin/glutamate receptor complex implicated in psychosis."
Gonzalez-Maeso J., Ang R.L., Yuen T., Chan P., Weisstaub N.V., Lopez-Gimenez J.F., Zhou M., Okawa Y., Callado L.F., Milligan G., Gingrich J.A., Filizola M., Meana J.J., Sealfon S.C.
Nature 452:93-97(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HTR2A, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[8]"Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A.mGlu2) receptor heteromerization and its psychoactive behavioral function."
Moreno J.L., Muguruza C., Umali A., Mortillo S., Holloway T., Pilar-Cuellar F., Mocci G., Seto J., Callado L.F., Neve R.L., Milligan G., Sealfon S.C., Lopez-Gimenez J.F., Meana J.J., Benson D.L., Gonzalez-Maeso J.
J. Biol. Chem. 287:44301-44319(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HTR2A, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ALA-677; ALA-681 AND ALA-685.
[9]"Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades."
Delille H.K., Becker J.M., Burkhardt S., Bleher B., Terstappen G.C., Schmidt M., Meyer A.H., Unger L., Marek G.J., Mezler M.
Neuropharmacology 62:2184-2191(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HTR2A, FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L35318 mRNA. Translation: AAA76855.1.
AB045011 Genomic DNA. Translation: BAB19817.1.
AY999299 mRNA. Translation: AAY14640.1.
EU432122 mRNA. Translation: ABY87921.1.
CH471055 Genomic DNA. Translation: EAW65150.1.
BC113615 mRNA. Translation: AAI13616.1.
BC113619 mRNA. Translation: AAI13620.1.
CCDSCCDS2834.1.
RefSeqNP_000830.2. NM_000839.3.
NP_001123535.1. NM_001130063.1.
XP_006713184.1. XM_006713121.1.
UniGeneHs.121510.

3D structure databases

ProteinModelPortalQ14416.
SMRQ14416. Positions 23-558.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59826N.
STRING9606.ENSP00000378492.

Chemistry

BindingDBQ14416.
ChEMBLCHEMBL5137.
DrugBankDB00659. Acamprosate.
DB00184. Nicotine.
GuidetoPHARMACOLOGY290.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ14416.

Polymorphism databases

DMDM76803802.

Proteomic databases

PaxDbQ14416.
PRIDEQ14416.

Protocols and materials databases

DNASU2912.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000395052; ENSP00000378492; ENSG00000164082.
GeneID2912.
KEGGhsa:2912.
UCSCuc010hlv.3. human.

Organism-specific databases

CTD2912.
GeneCardsGC03P051716.
HGNCHGNC:4594. GRM2.
MIM604099. gene.
neXtProtNX_Q14416.
PharmGKBPA28991.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295200.
HOGENOMHOG000218635.
HOVERGENHBG107965.
KOK04605.
OMAVTLKCNN.
OrthoDBEOG7Z0JXG.
PhylomeDBQ14416.
TreeFamTF313240.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ14416.
BgeeQ14416.
CleanExHS_GRM2.
GenevestigatorQ14416.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR000337. GPCR_3.
IPR011500. GPCR_3_9-Cys_dom.
IPR017978. GPCR_3_C.
IPR017979. GPCR_3_CS.
IPR000162. GPCR_3_mtglu_rcpt.
IPR001458. GPCR_3_mtglu_rcpt_2.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSPR00248. GPCRMGR.
PR01052. MTABOTROPC2R.
PR00593. MTABOTROPICR.
SUPFAMSSF53822. SSF53822. 1 hit.
PROSITEPS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMetabotropic_glutamate_receptor_2.
GenomeRNAi2912.
NextBio11543.
PROQ14416.
SOURCESearch...

Entry information

Entry nameGRM2_HUMAN
AccessionPrimary (citable) accession number: Q14416
Secondary accession number(s): B0M0K7 expand/collapse secondary AC list , Q14CU5, Q52MC6, Q9H3N6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 27, 2005
Last modified: July 9, 2014
This is version 113 of the entry and version 2 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

MIM cross-references

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

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Human chromosome 3: entries, gene names and cross-references to MIM

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