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Protein

Metabotropic glutamate receptor 5

Gene

Grm5

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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. 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.2 Publications

Miscellaneous

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei64GlutamateBy similarity1
Binding sitei151GlutamateBy similarity1
Binding sitei222GlutamateBy similarity1
Binding sitei304GlutamateBy similarity1
Binding sitei395GlutamateBy similarity1

GO - Molecular functioni

  • A2A adenosine receptor binding Source: RGD
  • calmodulin binding Source: UniProtKB
  • glutamate receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: UniProtKB
  • PDZ domain binding Source: UniProtKB
  • PLC activating G-protein coupled glutamate receptor activity Source: UniProtKB
  • protein tyrosine kinase binding Source: ARUK-UCL

GO - Biological processi

  • activation of MAPKKK activity Source: UniProtKB
  • adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: GO_Central
  • chemical synaptic transmission Source: RGD
  • desensitization of G-protein coupled receptor protein signaling pathway Source: UniProtKB
  • G-protein coupled glutamate receptor signaling pathway Source: UniProtKB
  • negative regulation of locomotion Source: RGD
  • phosphatidylinositol-mediated signaling Source: UniProtKB
  • phospholipase C-activating G-protein coupled glutamate receptor signaling pathway Source: UniProtKB
  • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: UniProtKB
  • positive regulation of long-term neuronal synaptic plasticity Source: RGD
  • positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
  • protein kinase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of synaptic transmission, glutamatergic Source: GO_Central
  • regulation of transcription, DNA-templated Source: RGD
  • trans-synaptic signaling by endocannabinoid, modulating synaptic transmission Source: SynGO

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 5
Short name:
mGluR5
Gene namesi
Name:Grm5
Synonyms:Gprc1e, Mglur5
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2746 Grm5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 579ExtracellularBy similarityAdd BLAST559
Transmembranei580 – 602Helical; Name=1By similarityAdd BLAST23
Topological domaini603 – 612CytoplasmicBy similarity10
Transmembranei613 – 635Helical; Name=2By similarityAdd BLAST23
Topological domaini636 – 643ExtracellularBy similarity8
Transmembranei644 – 666Helical; Name=3By similarityAdd BLAST23
Topological domaini667 – 692CytoplasmicBy similarityAdd BLAST26
Transmembranei693 – 713Helical; Name=4By similarityAdd BLAST21
Topological domaini714 – 736ExtracellularBy similarityAdd BLAST23
Transmembranei737 – 758Helical; Name=5By similarityAdd BLAST22
Topological domaini759 – 771CytoplasmicBy similarityAdd BLAST13
Transmembranei772 – 794Helical; Name=6By similarityAdd BLAST23
Topological domaini795 – 797ExtracellularBy similarity3
Transmembranei798 – 819Helical; Name=7By similarityAdd BLAST22
Topological domaini820 – 1203CytoplasmicBy similarityAdd BLAST384

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1154L → V: Normal binding to HOMER1. 1 Publication1
Mutagenesisi1156P → K: Disrupts binding to HOMER1. 1 Publication1
Mutagenesisi1157P → E: Disrupts binding to HOMER1. 1 Publication1
Mutagenesisi1157P → L: Disrupts binding to HOMER1. 1 Publication1
Mutagenesisi1158S → F: Normal binding to HOMER1. 1 Publication1
Mutagenesisi1159P → A: Normal binding to HOMER1. 1 Publication1
Mutagenesisi1160F → R: Disrupts binding to HOMER1. 1
Mutagenesisi1161R → T: Normal binding to HOMER1. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2564
GuidetoPHARMACOLOGYi293

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001293321 – 1203Metabotropic glutamate receptor 5Add BLAST1183

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi57 ↔ 99By similarity
Glycosylationi88N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi209N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi240 ↔ 529By similarity
Disulfide bondi275 ↔ 277By similarity
Disulfide bondi364 ↔ 380By similarity
Glycosylationi377N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi381N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi418 ↔ 425By similarity
Glycosylationi444N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi510 ↔ 530By similarity
Disulfide bondi514 ↔ 533By similarity
Disulfide bondi536 ↔ 548By similarity
Disulfide bondi551 ↔ 564By similarity
Disulfide bondi643 ↔ 732By similarity
Glycosylationi733N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei860PhosphoserineCombined sources1
Modified residuei868Omega-N-methylarginineBy similarity1
Modified residuei924Omega-N-methylarginineBy similarity1
Modified residuei1014PhosphoserineCombined sources1
Modified residuei1016PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

PaxDbiP31424
PRIDEiP31424

PTM databases

iPTMnetiP31424
PhosphoSitePlusiP31424

Expressioni

Tissue specificityi

Widely distributed in neuronal cells of the central nervous system.2 Publications

Gene expression databases

GenevisibleiP31424 RN

Interactioni

Subunit structurei

Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with SIAH1 and GRASP. Interacts with NCDN. Interacts with NECAB2.6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • A2A adenosine receptor binding Source: RGD
  • calmodulin binding Source: UniProtKB
  • PDZ domain binding Source: UniProtKB
  • protein tyrosine kinase binding Source: ARUK-UCL

Protein-protein interaction databases

BioGridi246583, 8 interactors
CORUMiP31424
DIPiDIP-41263N
ELMiP31424
IntActiP31424, 13 interactors
MINTiP31424
STRINGi10116.ENSRNOP00000022059

Chemistry databases

BindingDBiP31424

Structurei

3D structure databases

ProteinModelPortaliP31424
SMRiP31424
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31424

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni172 – 174Glutamate bindingBy similarity3
Regioni804 – 808Allosteric effector bindingBy similarity5

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056 Eukaryota
ENOG410XR6W LUCA
HOGENOMiHOG000218636
HOVERGENiHBG107965
InParanoidiP31424
KOiK04604
OrthoDBiEOG091G177R
PhylomeDBiP31424
TreeFamiTF313240

Family and domain databases

Gene3Di2.10.50.30, 1 hit
InterProiView protein in InterPro
IPR001828 ANF_lig-bd_rcpt
IPR000337 GPCR_3
IPR011500 GPCR_3_9-Cys_dom
IPR038550 GPCR_3_9-Cys_sf
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
PfamiView protein in Pfam
PF00003 7tm_3, 1 hit
PF01094 ANF_receptor, 1 hit
PF10606 GluR_Homer-bdg, 1 hit
PF07562 NCD3G, 1 hit
PRINTSiPR00248 GPCRMGR
PR01055 MTABOTROPC5R
PR00593 MTABOTROPICR
SMARTiView protein in SMART
SM01229 GluR_Homer-bdg, 1 hit
SUPFAMiSSF53822 SSF53822, 1 hit
PROSITEiView protein in PROSITE
PS00979 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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: P31424-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MVLLLILSVL LLKEDVRGSA QSSERRVVAH MPGDIIIGAL FSVHHQPTVD
60 70 80 90 100
KVHERKCGAV REQYGIQRVE AMLHTLERIN SDPTLLPNIT LGCEIRDSCW
110 120 130 140 150
HSAVALEQSI EFIRDSLISS EEEEGLVRCV DGSSSFRSKK PIVGVIGPGS
160 170 180 190 200
SSVAIQVQNL LQLFNIPQIA YSATSMDLSD KTLFKYFMRV VPSDAQQARA
210 220 230 240 250
MVDIVKRYNW TYVSAVHTEG NYGESGMEAF KDMSAKEGIC IAHSYKIYSN
260 270 280 290 300
AGEQSFDKLL KKLRSHLPKA RVVACFCEGM TVRGLLMAMR RLGLAGEFLL
310 320 330 340 350
LGSDGWADRY DVTDGYQREA VGGITIKLQS PDVKWFDDYY LKLRPETNLR
360 370 380 390 400
NPWFQEFWQH RFQCRLEGFA QENSKYNKTC NSSLTLRTHH VQDSKMGFVI
410 420 430 440 450
NAIYSMAYGL HNMQMSLCPG YAGLCDAMKP IDGRKLLDSL MKTNFTGVSG
460 470 480 490 500
DMILFDENGD SPGRYEIMNF KEMGKDYFDY INVGSWDNGE LKMDDDEVWS
510 520 530 540 550
KKNNIIRSVC SEPCEKGQIK VIRKGEVSCC WTCTPCKENE YVFDEYTCKA
560 570 580 590 600
CQLGSWPTDD LTGCDLIPVQ YLRWGDPEPI AAVVFACLGL LATLFVTVIF
610 620 630 640 650
IIYRDTPVVK SSSRELCYII LAGICLGYLC TFCLIAKPKQ IYCYLQRIGI
660 670 680 690 700
GLSPAMSYSA LVTKTNRIAR ILAGSKKKIC TKKPRFMSAC AQLVIAFILI
710 720 730 740 750
CIQLGIIVAL FIMEPPDIMH DYPSIREVYL ICNTTNLGVV TPLGYNGLLI
760 770 780 790 800
LSCTFYAFKT RNVPANFNEA KYIAFTMYTT CIIWLAFVPI YFGSNYKIIT
810 820 830 840 850
MCFSVSLSAT VALGCMFVPK VYIILAKPER NVRSAFTTST VVRMHVGDGK
860 870 880 890 900
SSSAASRSSS LVNLWKRRGS SGETLRYKDR RLAQHKSEIE CFTPKGSMGN
910 920 930 940 950
GGRATMSSSN GKSVTWAQNE KSTRGQHLWQ RLSVHINKKE NPNQTAVIKP
960 970 980 990 1000
FPKSTENRGP GAAAGGGSGP GVAGAGNAGC TATGGPEPPD AGPKALYDVA
1010 1020 1030 1040 1050
EAEESFPAAA RPRSPSPIST LSHLAGSAGR TDDDAPSLHS ETAARSSSSQ
1060 1070 1080 1090 1100
GSLMEQISSV VTRFTANISE LNSMMLSTAA TPGPPGTPIC SSYLIPKEIQ
1110 1120 1130 1140 1150
LPTTMTTFAE IQPLPAIEVT GGAQGATGVS PAQETPTGAE SAPGKPDLEE
1160 1170 1180 1190 1200
LVALTPPSPF RDSVDSGSTT PNSPVSESAL CIPSSPKYDT LIIRDYTQSS

SSL
Length:1,203
Mass (Da):131,885
Last modified:November 1, 1995 - v2
Checksum:i99CA51E9E11C1EA4
GO
Isoform 1 (identifier: P31424-2) [UniParc]FASTAAdd to basket
Also known as: 5a

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

Show »
Length:1,171
Mass (Da):128,290
Checksum:i8B43A7D33497C3AC
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002031876 – 907Missing in isoform 1. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10891 mRNA Translation: BAA01711.1
S64315 mRNA Translation: AAB27666.1
PIRiA42916
PN0549
RefSeqiNP_058708.1, NM_017012.1 [P31424-2]
XP_006229721.1, XM_006229659.3 [P31424-1]
XP_017444267.1, XM_017588778.1 [P31424-1]
XP_017444268.1, XM_017588779.1 [P31424-1]
XP_017444269.1, XM_017588780.1 [P31424-1]
XP_017444270.1, XM_017588781.1 [P31424-2]
UniGeneiRn.29972

Genome annotation databases

GeneIDi24418
KEGGirno:24418
UCSCiRGD:2746 rat [P31424-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiGRM5_RAT
AccessioniPrimary (citable) accession number: P31424
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 1, 1995
Last modified: June 20, 2018
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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

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