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Protein

Metabotropic glutamate receptor 2

Gene

GRM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei145 – 1451GlutamateBy similarity
Binding sitei216 – 2161GlutamateBy similarity
Binding sitei295 – 2951GlutamateBy similarity
Binding sitei377 – 3771GlutamateBy similarity

GO - Molecular functioni

  1. calcium channel regulator activity Source: GO_Central
  2. glutamate receptor activity Source: UniProtKB
  3. G-protein coupled receptor activity Source: UniProtKB
  4. group II metabotropic glutamate receptor activity Source: GO_Central

GO - Biological processi

  1. adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: GO_Central
  2. glutamate secretion Source: Ensembl
  3. negative regulation of adenylate cyclase activity Source: ProtInc
  4. regulation of synaptic transmission, glutamatergic Source: GO_Central
  5. synaptic transmission Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
REACT_19231. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 2
Short name:
mGluR2
Gene namesi
Name:GRM2
Synonyms:GPRC1B, MGLUR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:4594. GRM2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 567549ExtracellularSequence AnalysisAdd
BLAST
Transmembranei568 – 59023Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini591 – 60414CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei605 – 62521Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini626 – 63611ExtracellularSequence AnalysisAdd
BLAST
Transmembranei637 – 65519Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini656 – 67924CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei680 – 70021Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini701 – 72525ExtracellularSequence AnalysisAdd
BLAST
Transmembranei726 – 74722Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini748 – 76013CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei761 – 78323Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini784 – 79310ExtracellularSequence Analysis
Transmembranei794 – 81926Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini820 – 87253CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cell junction Source: UniProtKB-KW
  3. dendrite Source: UniProtKB-SubCell
  4. integral component of plasma membrane Source: GO_Central
  5. intracellular Source: Ensembl
  6. plasma membrane Source: Reactome
  7. presynaptic membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi677 – 6771A → S: Impairs interaction with HTR2A. 1 Publication
Mutagenesisi681 – 6811A → F: Impairs interaction with HTR2A. 1 Publication
Mutagenesisi685 – 6851A → G: Impairs interaction with HTR2A. 1 Publication

Organism-specific databases

PharmGKBiPA28991.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 872854Metabotropic glutamate receptor 2PRO_0000012925Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi50 ↔ 92By similarity
Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi234 ↔ 518By similarity
Glycosylationi286 – 2861N-linked (GlcNAc...)Sequence Analysis
Glycosylationi338 – 3381N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi355 ↔ 362By similarity
Disulfide bondi400 ↔ 407By similarity
Glycosylationi402 – 4021N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi500 ↔ 519By similarity
Disulfide bondi504 ↔ 522By similarity
Disulfide bondi525 ↔ 537By similarity
Disulfide bondi540 ↔ 553By similarity
Glycosylationi547 – 5471N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ14416.
PRIDEiQ14416.

PTM databases

PhosphoSiteiQ14416.

Expressioni

Tissue specificityi

Detected in brain cortex (at protein level). Widely expressed in different regions of the adult brain as well as in fetal brain.1 Publication

Gene expression databases

BgeeiQ14416.
CleanExiHS_GRM2.
ExpressionAtlasiQ14416. baseline and differential.
GenevestigatoriQ14416.

Interactioni

Subunit structurei

Interacts with GRASP (By similarity). Interacts with HTR2A.By similarity3 Publications

Protein-protein interaction databases

BioGridi109169. 2 interactions.
DIPiDIP-59826N.
STRINGi9606.ENSP00000378492.

Structurei

3D structure databases

ProteinModelPortaliQ14416.
SMRiQ14416. Positions 23-824.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni166 – 1683Glutamate bindingBy similarity
Regioni677 – 6859Important for interaction with HTR2A

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG295200.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14416.
KOiK04605.
OMAiTSQVVIC.
OrthoDBiEOG7Z0JXG.
PhylomeDBiQ14416.
TreeFamiTF313240.

Family and domain databases

InterProiIPR001828. 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]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01052. MTABOTROPC2R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q14416-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGSLLALLAL LLLWGAVAEG PAKKVLTLEG DLVLGGLFPV HQKGGPAEDC
60 70 80 90 100
GPVNEHRGIQ RLEAMLFALD RINRDPHLLP GVRLGAHILD SCSKDTHALE
110 120 130 140 150
QALDFVRASL SRGADGSRHI CPDGSYATHG DAPTAITGVI GGSYSDVSIQ
160 170 180 190 200
VANLLRLFQI PQISYASTSA KLSDKSRYDY FARTVPPDFF QAKAMAEILR
210 220 230 240 250
FFNWTYVSTV ASEGDYGETG IEAFELEARA RNICVATSEK VGRAMSRAAF
260 270 280 290 300
EGVVRALLQK PSARVAVLFT RSEDARELLA ASQRLNASFT WVASDGWGAL
310 320 330 340 350
ESVVAGSEGA AEGAITIELA SYPISDFASY FQSLDPWNNS RNPWFREFWE
360 370 380 390 400
QRFRCSFRQR DCAAHSLRAV PFEQESKIMF VVNAVYAMAH ALHNMHRALC
410 420 430 440 450
PNTTRLCDAM RPVNGRRLYK DFVLNVKFDA PFRPADTHNE VRFDRFGDGI
460 470 480 490 500
GRYNIFTYLR AGSGRYRYQK VGYWAEGLTL DTSLIPWASP SAGPLPASRC
510 520 530 540 550
SEPCLQNEVK SVQPGEVCCW LCIPCQPYEY RLDEFTCADC GLGYWPNASL
560 570 580 590 600
TGCFELPQEY IRWGDAWAVG PVTIACLGAL ATLFVLGVFV RHNATPVVKA
610 620 630 640 650
SGRELCYILL GGVFLCYCMT FIFIAKPSTA VCTLRRLGLG TAFSVCYSAL
660 670 680 690 700
LTKTNRIARI FGGAREGAQR PRFISPASQV AICLALISGQ LLIVVAWLVV
710 720 730 740 750
EAPGTGKETA PERREVVTLR CNHRDASMLG SLAYNVLLIA LCTLYAFKTR
760 770 780 790 800
KCPENFNEAK FIGFTMYTTC IIWLAFLPIF YVTSSDYRVQ TTTMCVSVSL
810 820 830 840 850
SGSVVLGCLF APKLHIILFQ PQKNVVSHRA PTSRFGSAAA RASSSLGQGS
860 870
GSQFVPTVCN GREVVDSTTS SL
Length:872
Mass (Da):95,568
Last modified:September 27, 2005 - v2
Checksum:i801976D034AA8100
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti12 – 121L → P in AAA76855. (PubMed:7620613)Curated
Sequence conflicti210 – 2101V → E in AAA76855. (PubMed:7620613)Curated
Sequence conflicti496 – 4961P → A in AAA76855. (PubMed:7620613)Curated
Sequence conflicti748 – 7481K → N in AAA76855. (PubMed:7620613)Curated
Sequence conflicti776 – 7761F → L in AAA76855. (PubMed:7620613)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2834.1.
RefSeqiNP_000830.2. NM_000839.3.
NP_001123535.1. NM_001130063.1.
XP_006713184.1. XM_006713121.1.
UniGeneiHs.121510.

Genome annotation databases

EnsembliENST00000395052; ENSP00000378492; ENSG00000164082.
GeneIDi2912.
KEGGihsa:2912.
UCSCiuc010hlv.3. human.

Polymorphism databases

DMDMi76803802.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2834.1.
RefSeqiNP_000830.2. NM_000839.3.
NP_001123535.1. NM_001130063.1.
XP_006713184.1. XM_006713121.1.
UniGeneiHs.121510.

3D structure databases

ProteinModelPortaliQ14416.
SMRiQ14416. Positions 23-824.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109169. 2 interactions.
DIPiDIP-59826N.
STRINGi9606.ENSP00000378492.

Chemistry

BindingDBiQ14416.
ChEMBLiCHEMBL5137.
GuidetoPHARMACOLOGYi290.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ14416.

Polymorphism databases

DMDMi76803802.

Proteomic databases

PaxDbiQ14416.
PRIDEiQ14416.

Protocols and materials databases

DNASUi2912.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395052; ENSP00000378492; ENSG00000164082.
GeneIDi2912.
KEGGihsa:2912.
UCSCiuc010hlv.3. human.

Organism-specific databases

CTDi2912.
GeneCardsiGC03P051716.
HGNCiHGNC:4594. GRM2.
MIMi604099. gene.
neXtProtiNX_Q14416.
PharmGKBiPA28991.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG295200.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14416.
KOiK04605.
OMAiTSQVVIC.
OrthoDBiEOG7Z0JXG.
PhylomeDBiQ14416.
TreeFamiTF313240.

Enzyme and pathway databases

ReactomeiREACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

GeneWikiiMetabotropic_glutamate_receptor_2.
GenomeRNAii2912.
NextBioi11543.
PROiQ14416.
SOURCEiSearch...

Gene expression databases

BgeeiQ14416.
CleanExiHS_GRM2.
ExpressionAtlasiQ14416. baseline and differential.
GenevestigatoriQ14416.

Family and domain databases

InterProiIPR001828. 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]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01052. MTABOTROPC2R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiGRM2_HUMAN
AccessioniPrimary (citable) accession number: Q14416
Secondary accession number(s): B0M0K7
, Q14CU5, Q52MC6, Q9H3N6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 27, 2005
Last modified: February 4, 2015
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.