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P31424 (GRM5_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metabotropic glutamate receptor 5

Short name=mGluR5
Gene names
Name:Grm5
Synonyms:Gprc1e, Mglur5
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1203 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. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity. Ref.1 Ref.7

Subunit structure

Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with SIAH1 and GRASP. Interacts with NCDN. Ref.3 Ref.4 Ref.5 Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

Widely distributed in neuronal cells of the central nervous system. Ref.1 Ref.7

Miscellaneous

Activated by quisqualate > glutamate > ibotenate > trans-1- aminocyclopentyl-1,3-dicarboxylate.

Sequence similarities

Belongs to the G-protein coupled receptor 3 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled glutamate receptor signaling pathway

Inferred from mutant phenotype Ref.1. Source: UniProtKB

activation of MAPKKK activity

Inferred from direct assay PubMed 15758184. Source: UniProtKB

desensitization of G-protein coupled receptor protein signaling pathway

Inferred from direct assay PubMed 12514208. Source: UniProtKB

learning

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of locomotion

Inferred from direct assay PubMed 12189203. Source: RGD

phosphatidylinositol-mediated signaling

Traceable author statement PubMed 15758184. Source: UniProtKB

phospholipase C-activating G-protein coupled glutamate receptor signaling pathway

Traceable author statement PubMed 12514208. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway

Traceable author statement PubMed 15758184. Source: UniProtKB

positive regulation of long-term neuronal synaptic plasticity

Inferred from direct assay PubMed 12740378. Source: RGD

protein kinase C-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 12514208. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 15758184. Source: UniProtKB

regulation of synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12189203. Source: RGD

synaptic transmission

Inferred from mutant phenotype PubMed 12514208. Source: RGD

   Cellular_componentastrocyte projection

Inferred from direct assay PubMed 21753079. Source: RGD

cytoplasm

Inferred from electronic annotation. Source: Ensembl

dendritic shaft

Inferred from direct assay PubMed 18582438. Source: RGD

dendritic spine

Inferred from direct assay PubMed 18582438. Source: RGD

integral component of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

membrane

Inferred from direct assay PubMed 12189203. Source: RGD

postsynaptic density

Inferred from direct assay PubMed 18582438. Source: RGD

postsynaptic membrane

Traceable author statement PubMed 10936169. Source: UniProtKB

   Molecular_functionA2A adenosine receptor binding

Inferred from physical interaction PubMed 12189203. Source: RGD

G-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Traceable author statement PubMed 10936169. Source: UniProtKB

PLC activating G-protein coupled glutamate receptor activity

Traceable author statement PubMed 12514208PubMed 15758184. Source: UniProtKB

calmodulin binding

Traceable author statement PubMed 12021391. Source: UniProtKB

glutamate receptor activity

Inferred from mutant phenotype Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12189203PubMed 23911326PubMed 24012003. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ADORA2AP292743EBI-2902778,EBI-2902702From a different organism.
FYNP062412EBI-8830305,EBI-515315From a different organism.
GraspQ8R4T55EBI-2902734,EBI-7361884
PIN1Q135263EBI-8830305,EBI-714158From a different organism.
Ppp1ccP6308819EBI-2902734,EBI-80049
PRNPP041564EBI-8830305,EBI-8830282From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: P31424-1)

Also known as: 5b;

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 1 (identifier: P31424-2)

Also known as: 5a;

The sequence of this isoform differs from the canonical sequence as follows:
     876-907: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 12031183Metabotropic glutamate receptor 5
PRO_0000012933

Regions

Topological domain22 – 578557Extracellular Potential
Transmembrane579 – 60123Helical; Name=1; Potential
Topological domain602 – 61514Cytoplasmic Potential
Transmembrane616 – 63621Helical; Name=2; Potential
Topological domain637 – 64711Extracellular Potential
Transmembrane648 – 66619Helical; Name=3; Potential
Topological domain667 – 69226Cytoplasmic Potential
Transmembrane693 – 71321Helical; Name=4; Potential
Topological domain714 – 73623Extracellular Potential
Transmembrane737 – 75822Helical; Name=5; Potential
Topological domain759 – 77113Cytoplasmic Potential
Transmembrane772 – 79423Helical; Name=6; Potential
Topological domain795 – 8006Extracellular Potential
Transmembrane801 – 82626Helical; Name=7; Potential
Topological domain827 – 1203377Cytoplasmic Potential
Region172 – 1743Glutamate binding By similarity

Sites

Binding site641Glutamate By similarity
Binding site1511Glutamate By similarity
Binding site2221Glutamate By similarity
Binding site3041Glutamate By similarity
Binding site3951Glutamate By similarity

Amino acid modifications

Glycosylation881N-linked (GlcNAc...) Potential
Glycosylation2091N-linked (GlcNAc...) Potential
Glycosylation3771N-linked (GlcNAc...) Potential
Glycosylation3811N-linked (GlcNAc...) Potential
Glycosylation4441N-linked (GlcNAc...) Potential
Glycosylation7331N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 99 By similarity
Disulfide bond240 ↔ 529 By similarity
Disulfide bond275 ↔ 277 By similarity
Disulfide bond364 ↔ 380 By similarity
Disulfide bond418 ↔ 425 By similarity
Disulfide bond510 ↔ 530 By similarity
Disulfide bond514 ↔ 533 By similarity
Disulfide bond536 ↔ 548 By similarity
Disulfide bond551 ↔ 564 By similarity

Natural variations

Alternative sequence876 – 90732Missing in isoform 1.
VSP_002031

Experimental info

Mutagenesis11541L → V: Normal binding to HOMER1. Ref.3
Mutagenesis11561P → K: Disrupts binding to HOMER1. Ref.3
Mutagenesis11571P → E: Disrupts binding to HOMER1. Ref.3
Mutagenesis11571P → L: Disrupts binding to HOMER1. Ref.3
Mutagenesis11581S → F: Normal binding to HOMER1. Ref.3
Mutagenesis11591P → A: Normal binding to HOMER1. Ref.3
Mutagenesis11601F → R: Disrupts binding to HOMER1.
Mutagenesis11611R → T: Normal binding to HOMER1. Ref.3

Secondary structure

... 1203
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (5b) [UniParc].

Last modified November 1, 1995. Version 2.
Checksum: 99CA51E9E11C1EA4

FASTA1,203131,885
        10         20         30         40         50         60 
MVLLLILSVL LLKEDVRGSA QSSERRVVAH MPGDIIIGAL FSVHHQPTVD KVHERKCGAV 

        70         80         90        100        110        120 
REQYGIQRVE AMLHTLERIN SDPTLLPNIT LGCEIRDSCW HSAVALEQSI EFIRDSLISS 

       130        140        150        160        170        180 
EEEEGLVRCV DGSSSFRSKK PIVGVIGPGS SSVAIQVQNL LQLFNIPQIA YSATSMDLSD 

       190        200        210        220        230        240 
KTLFKYFMRV VPSDAQQARA MVDIVKRYNW TYVSAVHTEG NYGESGMEAF KDMSAKEGIC 

       250        260        270        280        290        300 
IAHSYKIYSN AGEQSFDKLL KKLRSHLPKA RVVACFCEGM TVRGLLMAMR RLGLAGEFLL 

       310        320        330        340        350        360 
LGSDGWADRY DVTDGYQREA VGGITIKLQS PDVKWFDDYY LKLRPETNLR NPWFQEFWQH 

       370        380        390        400        410        420 
RFQCRLEGFA QENSKYNKTC NSSLTLRTHH VQDSKMGFVI NAIYSMAYGL HNMQMSLCPG 

       430        440        450        460        470        480 
YAGLCDAMKP IDGRKLLDSL MKTNFTGVSG DMILFDENGD SPGRYEIMNF KEMGKDYFDY 

       490        500        510        520        530        540 
INVGSWDNGE LKMDDDEVWS KKNNIIRSVC SEPCEKGQIK VIRKGEVSCC WTCTPCKENE 

       550        560        570        580        590        600 
YVFDEYTCKA CQLGSWPTDD LTGCDLIPVQ YLRWGDPEPI AAVVFACLGL LATLFVTVIF 

       610        620        630        640        650        660 
IIYRDTPVVK SSSRELCYII LAGICLGYLC TFCLIAKPKQ IYCYLQRIGI GLSPAMSYSA 

       670        680        690        700        710        720 
LVTKTNRIAR ILAGSKKKIC TKKPRFMSAC AQLVIAFILI CIQLGIIVAL FIMEPPDIMH 

       730        740        750        760        770        780 
DYPSIREVYL ICNTTNLGVV TPLGYNGLLI LSCTFYAFKT RNVPANFNEA KYIAFTMYTT 

       790        800        810        820        830        840 
CIIWLAFVPI YFGSNYKIIT MCFSVSLSAT VALGCMFVPK VYIILAKPER NVRSAFTTST 

       850        860        870        880        890        900 
VVRMHVGDGK SSSAASRSSS LVNLWKRRGS SGETLRYKDR RLAQHKSEIE CFTPKGSMGN 

       910        920        930        940        950        960 
GGRATMSSSN GKSVTWAQNE KSTRGQHLWQ RLSVHINKKE NPNQTAVIKP FPKSTENRGP 

       970        980        990       1000       1010       1020 
GAAAGGGSGP GVAGAGNAGC TATGGPEPPD AGPKALYDVA EAEESFPAAA RPRSPSPIST 

      1030       1040       1050       1060       1070       1080 
LSHLAGSAGR TDDDAPSLHS ETAARSSSSQ GSLMEQISSV VTRFTANISE LNSMMLSTAA 

      1090       1100       1110       1120       1130       1140 
TPGPPGTPIC SSYLIPKEIQ LPTTMTTFAE IQPLPAIEVT GGAQGATGVS PAQETPTGAE 

      1150       1160       1170       1180       1190       1200 
SAPGKPDLEE LVALTPPSPF RDSVDSGSTT PNSPVSESAL CIPSSPKYDT LIIRDYTQSS 


SSL 

« Hide

Isoform 1 (5a) [UniParc].

Checksum: 8B43A7D33497C3AC
Show »

FASTA1,171128,290

References

[1]"Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction."
Abe T., Sugihara H., Nawa H., Shigemoto R., Mizuno N., Nakanishi S.
J. Biol. Chem. 267:13361-13368(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon."
Minakami R., Katsuki F., Sugiyama H.
Biochem. Biophys. Res. Commun. 194:622-627(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 859-923, ALTERNATIVE SPLICING.
Tissue: Brain.
[3]"Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors."
Tu J.C., Xiao B., Yuan J.P., Lanahan A.A., Leoffert K., Li M., Linden D.J., Worley P.F.
Neuron 21:717-726(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOMER1; HOMER2 AND HOMER3, MUTAGENESIS OF LEU-1154; PRO-1156; PRO-1157; SER-1158; PRO-1159 AND ARG-1161.
[4]"Competitive interaction of seven in absentia homolog-1A and Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors."
Ishikawa K., Nash S.R., Nishimune A., Neki A., Kaneko S., Nakanishi S.
Genes Cells 4:381-390(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIAH1.
[5]"Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins."
Kitano J., Kimura K., Yamazaki Y., Soda T., Shigemoto R., Nakajima Y., Nakanishi S.
J. Neurosci. 22:1280-1289(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRASP.
[6]"Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling."
Wang H., Westin L., Nong Y., Birnbaum S., Bendor J., Brismar H., Nestler E., Aperia A., Flajolet M., Greengard P.
Science 326:1554-1557(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCDN.
[7]"Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses."
Verpelli C., Dvoretskova E., Vicidomini C., Rossi F., Chiappalone M., Schoen M., Di Stefano B., Mantegazza R., Broccoli V., Boeckers T.M., Dityatev A., Sala C.
J. Biol. Chem. 286:34839-34850(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SYNAPTIC ACTIVITY, TISSUE SPECIFICITY.
[8]"Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition."
Beneken J., Tu J.C., Xiao B., Nuriya M., Yuan J.P., Worley P.F., Leahy D.J.
Neuron 26:143-154(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1155-1160 IN COMPLEX WITH HOMER1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D10891 mRNA. Translation: BAA01711.1.
S64315 mRNA. Translation: AAB27666.1.
PIRA42916.
PN0549.
RefSeqNP_058708.1. NM_017012.1. [P31424-2]
XP_006229717.1. XM_006229655.1. [P31424-1]
XP_006229718.1. XM_006229656.1. [P31424-1]
XP_006229719.1. XM_006229657.1. [P31424-1]
XP_006229720.1. XM_006229658.1. [P31424-1]
XP_006229721.1. XM_006229659.1. [P31424-1]
XP_006229722.1. XM_006229660.1. [P31424-2]
UniGeneRn.29972.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DDVX-ray1.90B1155-1160[»]
ProteinModelPortalP31424.
SMRP31424. Positions 25-498.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246583. 7 interactions.
DIPDIP-41263N.
IntActP31424. 10 interactions.
MINTMINT-235173.

Chemistry

BindingDBP31424.
ChEMBLCHEMBL2111335.
GuidetoPHARMACOLOGY293.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP31424.

Proteomic databases

PaxDbP31424.
PRIDEP31424.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000022060; ENSRNOP00000022059; ENSRNOG00000016429. [P31424-1]
ENSRNOT00000050639; ENSRNOP00000040016; ENSRNOG00000016429. [P31424-2]
GeneID24418.
KEGGrno:24418.
UCSCRGD:2746. rat. [P31424-1]

Organism-specific databases

CTD2915.
RGD2746. Grm5.

Phylogenomic databases

eggNOGNOG295200.
GeneTreeENSGT00750000117484.
HOGENOMHOG000218636.
HOVERGENHBG107965.
InParanoidP31424.
KOK04604.
OMAAPLCSSY.
OrthoDBEOG7Z0JXG.
PhylomeDBP31424.
TreeFamTF313240.

Gene expression databases

GenevestigatorP31424.

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.
IPR000202. GPCR_3_mtglu_rcpt_5.
IPR019588. Metabotropic_Glu_rcpt_Homer-bd.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF10606. GluR_Homer-bdg. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSPR00248. GPCRMGR.
PR01055. MTABOTROPC5R.
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

EvolutionaryTraceP31424.
NextBio603267.
PROP31424.

Entry information

Entry nameGRM5_RAT
AccessionPrimary (citable) accession number: P31424
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 1, 1995
Last modified: June 11, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries