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P41594 (GRM5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1212 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

Subunit structure

The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with SIAH1, RYR1, RYR2, ITPR1, SHANK1, SHANK3 and GRASP. Interacts with NCDN By similarity.

Subcellular location

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

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 electronic annotation. Source: Ensembl

desensitization of G-protein coupled receptor protein signaling pathway

Inferred from electronic annotation. Source: Ensembl

learning

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of locomotion

Inferred from electronic annotation. Source: Ensembl

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

Traceable author statement Ref.1. Source: ProtInc

positive regulation of long-term neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentastrocyte projection

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: Ensembl

dendritic shaft

Inferred from electronic annotation. Source: Ensembl

dendritic spine

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Inferred from mutant phenotype Ref.1. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic density

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionG-protein coupled receptor activity

Traceable author statement Ref.1. Source: UniProtKB

glutamate receptor activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: P41594-1)

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: P41594-2)

Also known as: 5a;

The sequence of this isoform differs from the canonical sequence as follows:
     877-908: Missing.
Isoform 3 (identifier: P41594-3)

Also known as: 5d;

The sequence of this isoform differs from the canonical sequence as follows:
     896-1165: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 12121192Metabotropic glutamate receptor 5
PRO_0000012932

Regions

Topological domain22 – 579558Extracellular Potential
Transmembrane580 – 60223Helical; Name=1; Potential
Topological domain603 – 61614Cytoplasmic Potential
Transmembrane617 – 63721Helical; Name=2; Potential
Topological domain638 – 64811Extracellular Potential
Transmembrane649 – 66719Helical; Name=3; Potential
Topological domain668 – 69326Cytoplasmic Potential
Transmembrane694 – 71421Helical; Name=4; Potential
Topological domain715 – 73723Extracellular Potential
Transmembrane738 – 75922Helical; Name=5; Potential
Topological domain760 – 77213Cytoplasmic Potential
Transmembrane773 – 79523Helical; Name=6; Potential
Topological domain796 – 8016Extracellular Potential
Transmembrane802 – 82726Helical; Name=7; Potential
Topological domain828 – 1212385Cytoplasmic Potential
Region173 – 1753Glutamate binding

Sites

Binding site641Glutamate
Binding site1521Glutamate
Binding site2231Glutamate
Binding site3051Glutamate
Binding site3961Glutamate

Amino acid modifications

Glycosylation881N-linked (GlcNAc...) Potential
Glycosylation2101N-linked (GlcNAc...) Potential
Glycosylation3781N-linked (GlcNAc...) Potential
Glycosylation3821N-linked (GlcNAc...) Potential
Glycosylation4451N-linked (GlcNAc...) Ref.6
Glycosylation7341N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 99 Ref.6
Disulfide bond241 ↔ 530 By similarity
Disulfide bond276 ↔ 278 Ref.6
Disulfide bond365 ↔ 381 Ref.6
Disulfide bond419 ↔ 426 Ref.6
Disulfide bond511 ↔ 531 By similarity
Disulfide bond515 ↔ 534 By similarity
Disulfide bond537 ↔ 549 By similarity
Disulfide bond552 ↔ 565 By similarity

Natural variations

Alternative sequence877 – 90832Missing in isoform 1.
VSP_002030
Alternative sequence896 – 1165270Missing in isoform 3.
VSP_047710

Secondary structure

................................................................................ 1212
Helix Strand Turn

Details...

Sequences

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

Last modified October 1, 1996. Version 2.
Checksum: A3C73606681C6A25

FASTA1,212132,469
        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 DGSSSSFRSK KPIVGVIGPG SSSVAIQVQN LLQLFNIPQI AYSATSMDLS 

       190        200        210        220        230        240 
DKTLFKYFMR VVPSDAQQAR AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI 

       250        260        270        280        290        300 
CIAHSYKIYS NAGEQSFDKL LKKLTSHLPK ARVVACFCEG MTVRGLLMAM RRLGLAGEFL 

       310        320        330        340        350        360 
LLGSDGWADR YDVTDGYQRE AVGGITIKLQ SPDVKWFDDY YLKLRPETNH RNPWFQEFWQ 

       370        380        390        400        410        420 
HRFQCRLEGF PQENSKYNKT CNSSLTLKTH HVQDSKMGFV INAIYSMAYG LHNMQMSLCP 

       430        440        450        460        470        480 
GYAGLCDAMK PIDGRKLLES LMKTNFTGVS GDTILFDENG DSPGRYEIMN FKEMGKDYFD 

       490        500        510        520        530        540 
YINVGSWDNG ELKMDDDEVW SKKSNIIRSV CSEPCEKGQI KVIRKGEVSC CWTCTPCKEN 

       550        560        570        580        590        600 
EYVFDEYTCK ACQLGSWPTD DLTGCDLIPV QYLRWGDPEP IAAVVFACLG LLATLFVTVV 

       610        620        630        640        650        660 
FIIYRDTPVV KSSSRELCYI ILAGICLGYL CTFCLIAKPK QIYCYLQRIG IGLSPAMSYS 

       670        680        690        700        710        720 
ALVTKTNRIA RILAGSKKKI CTKKPRFMSA CAQLVIAFIL ICIQLGIIVA LFIMEPPDIM 

       730        740        750        760        770        780 
HDYPSIREVY LICNTTNLGV VTPLGYNGLL ILSCTFYAFK TRNVPANFNE AKYIAFTMYT 

       790        800        810        820        830        840 
TCIIWLAFVP IYFGSNYKII TMCFSVSLSA TVALGCMFVP KVYIILAKPE RNVRSAFTTS 

       850        860        870        880        890        900 
TVVRMHVGDG KSSSAASRSS SLVNLWKRRG SSGETLRYKD RRLAQHKSEI ECFTPKGSMG 

       910        920        930        940        950        960 
NGGRATMSSS NGKSVTWAQN EKSSRGQHLW QRLSIHINKK ENPNQTAVIK PFPKSTESRG 

       970        980        990       1000       1010       1020 
LGAGAGAGGS AGGVGATGGA GCAGAGPGGP ESPDAGPKAL YDVAEAEEHF PAPARPRSPS 

      1030       1040       1050       1060       1070       1080 
PISTLSHRAG SASRTDDDVP SLHSEPVARS SSSQGSLMEQ ISSVVTRFTA NISELNSMML 

      1090       1100       1110       1120       1130       1140 
STAAPSPGVG APLCSSYLIP KEIQLPTTMT TFAEIQPLPA IEVTGGAQPA AGAQAAGDAA 

      1150       1160       1170       1180       1190       1200 
RESPAAGPEA AAAKPDLEEL VALTPPSPFR DSVDSGSTTP NSPVSESALC IPSSPKYDTL 

      1210 
IIRDYTQSSS SL 

« Hide

Isoform 1 (5a) [UniParc].

Checksum: 3DBACB2E8B341647
Show »

FASTA1,180128,874
Isoform 3 (5d) [UniParc].

Checksum: EF45A35CADD56535
Show »

FASTA942105,432

References

« Hide 'large scale' references
[1]"Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5."
Minakami R., Katsuki F., Yamamoto T., Nakamura K., Sugiyama H.
Biochem. Biophys. Res. Commun. 199:1136-1143(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION.
Tissue: Brain.
[2]Katsuki F.
Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Molecular cloning and characterization of human metabotropic glutamate receptor 5d; a splice variant with reduced desensitization properties."
Levinthal C., Storjohann L., Hammerland L.G., Hung B.C.P., Krapcho K.J., Logan M.A., Smith D.L., Trovato R., Vanwagenen B.C., Stormannn T.M.
Abstr. - Soc. Neurosci. 25:976-976(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[4]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 860-952 (ISOFORM 2).
Tissue: Brain.
[6]"Metabotropic glutamate receptor MGluR5 complexed with glutamate."
Structural genomics consortium (SGC)
Submitted (JUL-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 18-505 IN COMPLEX WITH GLUTAMATE, GLYCOSYLATION AT ASN-445, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D28538 mRNA. Translation: BAA05891.1.
D28539 mRNA. Translation: BAA05892.1.
AY608336 mRNA. Translation: AAT37960.1.
AP000626 Genomic DNA. No translation available.
AP001482 Genomic DNA. No translation available.
AP001828 Genomic DNA. No translation available.
AP003120 Genomic DNA. No translation available.
AP006214 Genomic DNA. No translation available.
AP006215 Genomic DNA. No translation available.
S64316 mRNA. Translation: AAD13954.1.
PIRJC2131.
JC2132.
RefSeqNP_000833.1. NM_000842.3.
NP_001137303.1. NM_001143831.2.
UniGeneHs.147361.
Hs.616625.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3LMKX-ray2.44A/B18-505[»]
ProteinModelPortalP41594.
SMRP41594. Positions 26-569.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109172. 4 interactions.
STRING9606.ENSP00000306138.

Chemistry

BindingDBP41594.
ChEMBLCHEMBL3227.
DrugBankDB00659. Acamprosate.
GuidetoPHARMACOLOGY293.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP41594.

Polymorphism databases

DMDM1709020.

Proteomic databases

PaxDbP41594.
PRIDEP41594.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000305432; ENSP00000305905; ENSG00000168959. [P41594-2]
ENST00000305447; ENSP00000306138; ENSG00000168959. [P41594-1]
ENST00000393297; ENSP00000376975; ENSG00000168959. [P41594-3]
ENST00000418177; ENSP00000402912; ENSG00000168959. [P41594-1]
ENST00000455756; ENSP00000405690; ENSG00000168959. [P41594-2]
GeneID2915.
KEGGhsa:2915.
UCSCuc001pcq.3. human. [P41594-1]
uc009yvm.3. human. [P41594-2]

Organism-specific databases

CTD2915.
GeneCardsGC11M088237.
HGNCHGNC:4597. GRM5.
HPAHPA014096.
MIM604102. gene.
neXtProtNX_P41594.
PharmGKBPA28994.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295200.
HOGENOMHOG000218636.
HOVERGENHBG107965.
InParanoidP41594.
KOK04604.
OMAAPLCSSY.
OrthoDBEOG7Z0JXG.
PhylomeDBP41594.
TreeFamTF313240.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP41594.

Gene expression databases

ArrayExpressP41594.
BgeeP41594.
CleanExHS_GRM5.
GenevestigatorP41594.

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

ChiTaRSGRM5. human.
EvolutionaryTraceP41594.
GenomeRNAi2915.
NextBio11555.
PROP41594.
SOURCESearch...

Entry information

Entry nameGRM5_HUMAN
AccessionPrimary (citable) accession number: P41594
Secondary accession number(s): Q6J164
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 132 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries