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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)DescriptionActionsGraphical viewLength
Binding sitei145GlutamateBy similarity1
Binding sitei216GlutamateBy similarity1
Binding sitei295GlutamateBy similarity1
Binding sitei377GlutamateBy similarity1

GO - Molecular functioni

  • calcium channel regulator activity Source: GO_Central
  • glutamate receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: UniProtKB
  • group II metabotropic glutamate receptor activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164082-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SIGNORiQ14416.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:4594. GRM2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 567ExtracellularSequence analysisAdd BLAST549
Transmembranei568 – 590Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini591 – 604CytoplasmicSequence analysisAdd BLAST14
Transmembranei605 – 625Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini626 – 636ExtracellularSequence analysisAdd BLAST11
Transmembranei637 – 655Helical; Name=3Sequence analysisAdd BLAST19
Topological domaini656 – 679CytoplasmicSequence analysisAdd BLAST24
Transmembranei680 – 700Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini701 – 725ExtracellularSequence analysisAdd BLAST25
Transmembranei726 – 747Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini748 – 760CytoplasmicSequence analysisAdd BLAST13
Transmembranei761 – 783Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini784 – 793ExtracellularSequence analysis10
Transmembranei794 – 819Helical; Name=7Sequence analysisAdd BLAST26
Topological domaini820 – 872CytoplasmicSequence analysisAdd BLAST53

GO - Cellular componenti

  • axon Source: Ensembl
  • cell junction Source: UniProtKB-KW
  • dendrite Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • intracellular Source: Ensembl
  • plasma membrane Source: Reactome
  • 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)DescriptionActionsGraphical viewLength
Mutagenesisi677A → S: Impairs interaction with HTR2A. 1 Publication1
Mutagenesisi681A → F: Impairs interaction with HTR2A. 1 Publication1
Mutagenesisi685A → G: Impairs interaction with HTR2A. 1 Publication1

Organism-specific databases

DisGeNETi2912.
OpenTargetsiENSG00000164082.
PharmGKBiPA28991.

Chemistry databases

ChEMBLiCHEMBL5137.
GuidetoPHARMACOLOGYi290.

Polymorphism and mutation databases

BioMutaiGRM2.
DMDMi76803802.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001292519 – 872Metabotropic glutamate receptor 2Add BLAST854

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi50 ↔ 92By similarity
Glycosylationi203N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi234 ↔ 518By similarity
Glycosylationi286N-linked (GlcNAc...)Sequence analysis1
Glycosylationi338N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi355 ↔ 362By similarity
Disulfide bondi400 ↔ 407By similarity
Glycosylationi402N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi500 ↔ 519By similarity
Disulfide bondi504 ↔ 522By similarity
Disulfide bondi525 ↔ 537By similarity
Disulfide bondi540 ↔ 553By similarity
Glycosylationi547N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ14416.
PeptideAtlasiQ14416.
PRIDEiQ14416.

PTM databases

iPTMnetiQ14416.
PhosphoSitePlusiQ14416.

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

BgeeiENSG00000164082.
CleanExiHS_GRM2.
ExpressionAtlasiQ14416. baseline and differential.
GenevisibleiQ14416. HS.

Organism-specific databases

HPAiHPA065166.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
NAALADL2Q58DX53EBI-10232876,EBI-10178964
UBQLN1Q9UMX0-23EBI-10232876,EBI-10173939

Protein-protein interaction databases

BioGridi109169. 4 interactors.
DIPiDIP-59826N.
IntActiQ14416. 3 interactors.
STRINGi9606.ENSP00000378492.

Chemistry databases

BindingDBiQ14416.

Structurei

Secondary structure

1872
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 28Combined sources3
Beta strandi31 – 38Combined sources8
Beta strandi41 – 43Combined sources3
Beta strandi49 – 53Combined sources5
Turni55 – 58Combined sources4
Helixi59 – 74Combined sources16
Beta strandi76 – 81Combined sources6
Beta strandi84 – 90Combined sources7
Helixi95 – 106Combined sources12
Turni107 – 109Combined sources3
Beta strandi138 – 140Combined sources3
Helixi145 – 155Combined sources11
Helixi156 – 158Combined sources3
Beta strandi162 – 166Combined sources5
Helixi170 – 173Combined sources4
Turni175 – 177Combined sources3
Beta strandi181 – 185Combined sources5
Helixi188 – 202Combined sources15
Beta strandi206 – 214Combined sources9
Helixi217 – 230Combined sources14
Beta strandi234 – 241Combined sources8
Helixi247 – 258Combined sources12
Beta strandi260 – 262Combined sources3
Beta strandi265 – 269Combined sources5
Helixi272 – 284Combined sources13
Beta strandi290 – 293Combined sources4
Turni295 – 299Combined sources5
Helixi301 – 304Combined sources4
Helixi308 – 311Combined sources4
Beta strandi315 – 320Combined sources6
Helixi327 – 332Combined sources6
Turni336 – 338Combined sources3
Helixi345 – 352Combined sources8
Beta strandi357 – 359Combined sources3
Turni367 – 369Combined sources3
Helixi378 – 399Combined sources22
Helixi408 – 410Combined sources3
Helixi415 – 421Combined sources7
Helixi423 – 425Combined sources3
Beta strandi427 – 429Combined sources3
Beta strandi440 – 442Combined sources3
Beta strandi453 – 460Combined sources8
Beta strandi466 – 480Combined sources15
Helixi482 – 484Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4XAQX-ray2.21A/B2-493[»]
4XASX-ray2.35A/B2-493[»]
5CNIX-ray2.69A/B2-493[»]
5CNJX-ray2.65A/B2-493[»]
ProteinModelPortaliQ14416.
SMRiQ14416.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 168Glutamate bindingBy similarity3
Regioni677 – 685Important for interaction with HTR2A9

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14416.
KOiK04605.
OMAiCSDPCKK.
OrthoDBiEOG091G177R.
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)DescriptionActionsGraphical viewLength
Sequence conflicti12L → P in AAA76855 (PubMed:7620613).Curated1
Sequence conflicti210V → E in AAA76855 (PubMed:7620613).Curated1
Sequence conflicti496P → A in AAA76855 (PubMed:7620613).Curated1
Sequence conflicti748K → N in AAA76855 (PubMed:7620613).Curated1
Sequence conflicti776F → L in AAA76855 (PubMed:7620613).Curated1

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_016861760.1. XM_017006271.1.
UniGeneiHs.121510.

Genome annotation databases

EnsembliENST00000395052; ENSP00000378492; ENSG00000164082.
GeneIDi2912.
KEGGihsa:2912.
UCSCiuc010hlv.4. human.

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_016861760.1. XM_017006271.1.
UniGeneiHs.121510.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4XAQX-ray2.21A/B2-493[»]
4XASX-ray2.35A/B2-493[»]
5CNIX-ray2.69A/B2-493[»]
5CNJX-ray2.65A/B2-493[»]
ProteinModelPortaliQ14416.
SMRiQ14416.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109169. 4 interactors.
DIPiDIP-59826N.
IntActiQ14416. 3 interactors.
STRINGi9606.ENSP00000378492.

Chemistry databases

BindingDBiQ14416.
ChEMBLiCHEMBL5137.
GuidetoPHARMACOLOGYi290.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ14416.
PhosphoSitePlusiQ14416.

Polymorphism and mutation databases

BioMutaiGRM2.
DMDMi76803802.

Proteomic databases

PaxDbiQ14416.
PeptideAtlasiQ14416.
PRIDEiQ14416.

Protocols and materials databases

DNASUi2912.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395052; ENSP00000378492; ENSG00000164082.
GeneIDi2912.
KEGGihsa:2912.
UCSCiuc010hlv.4. human.

Organism-specific databases

CTDi2912.
DisGeNETi2912.
GeneCardsiGRM2.
HGNCiHGNC:4594. GRM2.
HPAiHPA065166.
MIMi604099. gene.
neXtProtiNX_Q14416.
OpenTargetsiENSG00000164082.
PharmGKBiPA28991.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiQ14416.
KOiK04605.
OMAiCSDPCKK.
OrthoDBiEOG091G177R.
PhylomeDBiQ14416.
TreeFamiTF313240.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164082-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
SIGNORiQ14416.

Miscellaneous databases

GeneWikiiMetabotropic_glutamate_receptor_2.
GenomeRNAii2912.
PROiQ14416.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164082.
CleanExiHS_GRM2.
ExpressionAtlasiQ14416. baseline and differential.
GenevisibleiQ14416. HS.

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...

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: November 30, 2016
This is version 135 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.