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Protein

Metabotropic glutamate receptor 5

Gene

GRM5

Organism
Homo sapiens (Human)
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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei64Glutamate1 Publication1
Binding sitei152Glutamate1 Publication1
Binding sitei223Glutamate1 Publication1
Binding sitei305Glutamate1 Publication1
Binding sitei396Glutamate1 Publication1

GO - Molecular functioni

  • glutamate receptor activity Source: UniProtKB
  • G protein-coupled receptor activity Source: UniProtKB
  • G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential Source: GO_Central
  • neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration Source: GO_Central
  • protein tyrosine kinase activator activity Source: ARUK-UCL
  • protein tyrosine kinase binding Source: ARUK-UCL

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-416476 G alpha (q) signalling events
R-HSA-420499 Class C/3 (Metabotropic glutamate/pheromone receptors)
R-HSA-6794361 Neurexins and neuroligins
SignaLinkiP41594
SIGNORiP41594

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 5
Short name:
mGluR5
Gene namesi
Name:GRM5
Synonyms:GPRC1E, MGLUR5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000168959.14
HGNCiHGNC:4597 GRM5
MIMi604102 gene
neXtProtiNX_P41594

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 domaini22 – 580Extracellular1 PublicationAdd BLAST559
Transmembranei581 – 603Helical; Name=1Add BLAST23
Topological domaini604 – 613Cytoplasmic1 Publication10
Transmembranei614 – 636Helical; Name=2Add BLAST23
Topological domaini637 – 644Extracellular1 Publication8
Transmembranei645 – 667Helical; Name=3Add BLAST23
Topological domaini668 – 693Cytoplasmic1 PublicationAdd BLAST26
Transmembranei694 – 714Helical; Name=4Add BLAST21
Topological domaini715 – 737Extracellular1 PublicationAdd BLAST23
Transmembranei738 – 759Helical; Name=5Add BLAST22
Topological domaini760 – 772Cytoplasmic1 PublicationAdd BLAST13
Transmembranei773 – 795Helical; Name=6Add BLAST23
Topological domaini796 – 798Extracellular1 Publication3
Transmembranei799 – 820Helical; Name=7Add BLAST22
Topological domaini821 – 1212Cytoplasmic1 PublicationAdd BLAST392

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi613S → A or K: Increased constitutive signaling activity. 1 Publication1
Mutagenesisi614S → D: Decreased constitutive signaling activity. 1 Publication1
Mutagenesisi665K → A: Increased constitutive signaling activity. 1 Publication1
Mutagenesisi770E → A: Increased constitutive signaling activity. 1 Publication1

Organism-specific databases

DisGeNETi2915
OpenTargetsiENSG00000168959
PharmGKBiPA28994

Chemistry databases

ChEMBLiCHEMBL3227
DrugBankiDB00659 Acamprosate
DB06060 ADX-48621
DB05070 ADX10059
DB06201 Rufinamide
GuidetoPHARMACOLOGYi293

Polymorphism and mutation databases

BioMutaiGRM5
DMDMi1709020

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001293221 – 1212Metabotropic glutamate receptor 5Add BLAST1192

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi57 ↔ 99
Glycosylationi88N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi210N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi241 ↔ 530By similarity
Disulfide bondi276 ↔ 278
Disulfide bondi365 ↔ 381
Glycosylationi378N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi382N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi419 ↔ 426
Glycosylationi445N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi511 ↔ 531By similarity
Disulfide bondi515 ↔ 534By similarity
Disulfide bondi537 ↔ 549By similarity
Disulfide bondi552 ↔ 565By similarity
Disulfide bondi644 ↔ 733
Glycosylationi734N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei861PhosphoserineBy similarity1
Modified residuei869Omega-N-methylarginineBy similarity1
Modified residuei925Omega-N-methylarginineBy similarity1
Modified residuei1018PhosphoserineBy similarity1
Modified residuei1020PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

PaxDbiP41594
PeptideAtlasiP41594
PRIDEiP41594
ProteomicsDBi55471
55472 [P41594-2]

PTM databases

iPTMnetiP41594
PhosphoSitePlusiP41594

Expressioni

Gene expression databases

BgeeiENSG00000168959 Expressed in 113 organ(s), highest expression level in frontal cortex
CleanExiHS_GRM5
ExpressionAtlasiP41594 baseline and differential
GenevisibleiP41594 HS

Interactioni

Subunit structurei

The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with SIAH1, RYR1, RYR2, ITPR1, SHANK1, SHANK3 and GRASP. Interacts with NCDN (By similarity). Isoform 2 interacts with NECAB2 (PubMed:19694902). Interacts with CAMK2A (PubMed:28130356).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NECAB2Q7Z6G32EBI-14039683,EBI-950070

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109172, 8 interactors
IntActiP41594, 5 interactors
STRINGi9606.ENSP00000306138

Chemistry databases

BindingDBiP41594

Structurei

Secondary structure

11212
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP41594
SMRiP41594
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP41594

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni173 – 175Glutamate binding3
Regioni805 – 809Allosteric effector binding5

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056 Eukaryota
ENOG410XR6W LUCA
GeneTreeiENSGT00760000118884
HOGENOMiHOG000218636
HOVERGENiHBG107965
InParanoidiP41594
KOiK04604
OMAiDLTGCDP
OrthoDBiEOG091G177R
PhylomeDBiP41594
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 (3+)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 2 (identifier: P41594-1) [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 DGSSSSFRSK KPIVGVIGPG
160 170 180 190 200
SSSVAIQVQN LLQLFNIPQI AYSATSMDLS DKTLFKYFMR VVPSDAQQAR
210 220 230 240 250
AMVDIVKRYN WTYVSAVHTE GNYGESGMEA FKDMSAKEGI CIAHSYKIYS
260 270 280 290 300
NAGEQSFDKL LKKLTSHLPK ARVVACFCEG MTVRGLLMAM RRLGLAGEFL
310 320 330 340 350
LLGSDGWADR YDVTDGYQRE AVGGITIKLQ SPDVKWFDDY YLKLRPETNH
360 370 380 390 400
RNPWFQEFWQ HRFQCRLEGF PQENSKYNKT CNSSLTLKTH HVQDSKMGFV
410 420 430 440 450
INAIYSMAYG LHNMQMSLCP GYAGLCDAMK PIDGRKLLES LMKTNFTGVS
460 470 480 490 500
GDTILFDENG DSPGRYEIMN FKEMGKDYFD YINVGSWDNG ELKMDDDEVW
510 520 530 540 550
SKKSNIIRSV CSEPCEKGQI KVIRKGEVSC CWTCTPCKEN EYVFDEYTCK
560 570 580 590 600
ACQLGSWPTD DLTGCDLIPV QYLRWGDPEP IAAVVFACLG LLATLFVTVV
610 620 630 640 650
FIIYRDTPVV KSSSRELCYI ILAGICLGYL CTFCLIAKPK QIYCYLQRIG
660 670 680 690 700
IGLSPAMSYS ALVTKTNRIA RILAGSKKKI CTKKPRFMSA CAQLVIAFIL
710 720 730 740 750
ICIQLGIIVA LFIMEPPDIM HDYPSIREVY LICNTTNLGV VTPLGYNGLL
760 770 780 790 800
ILSCTFYAFK TRNVPANFNE AKYIAFTMYT TCIIWLAFVP IYFGSNYKII
810 820 830 840 850
TMCFSVSLSA TVALGCMFVP KVYIILAKPE RNVRSAFTTS TVVRMHVGDG
860 870 880 890 900
KSSSAASRSS SLVNLWKRRG SSGETLRYKD RRLAQHKSEI ECFTPKGSMG
910 920 930 940 950
NGGRATMSSS NGKSVTWAQN EKSSRGQHLW QRLSIHINKK ENPNQTAVIK
960 970 980 990 1000
PFPKSTESRG LGAGAGAGGS AGGVGATGGA GCAGAGPGGP ESPDAGPKAL
1010 1020 1030 1040 1050
YDVAEAEEHF PAPARPRSPS PISTLSHRAG SASRTDDDVP SLHSEPVARS
1060 1070 1080 1090 1100
SSSQGSLMEQ ISSVVTRFTA NISELNSMML STAAPSPGVG APLCSSYLIP
1110 1120 1130 1140 1150
KEIQLPTTMT TFAEIQPLPA IEVTGGAQPA AGAQAAGDAA RESPAAGPEA
1160 1170 1180 1190 1200
AAAKPDLEEL VALTPPSPFR DSVDSGSTTP NSPVSESALC IPSSPKYDTL
1210
IIRDYTQSSS SL
Length:1,212
Mass (Da):132,469
Last modified:October 1, 1996 - v2
Checksum:iA3C73606681C6A25
GO
Isoform 1 (identifier: P41594-2) [UniParc]FASTAAdd to basket
Also known as: 5a

The sequence of this isoform differs from the canonical sequence as follows:
     877-908: Missing.

Show »
Length:1,180
Mass (Da):128,874
Checksum:i3DBACB2E8B341647
GO
Isoform 3 (identifier: P41594-3) [UniParc]FASTAAdd to basket
Also known as: 5d

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

Show »
Length:942
Mass (Da):105,432
Checksum:iEF45A35CADD56535
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A8MT20A8MT20_HUMAN
Metabotropic glutamate receptor 5
GRM5
298Annotation score:
H7C223H7C223_HUMAN
Metabotropic glutamate receptor 5
GRM5
87Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002030877 – 908Missing in isoform 1. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_047710896 – 1165Missing in isoform 3. 1 PublicationAdd BLAST270

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS44694.1 [P41594-1]
CCDS8283.1 [P41594-2]
PIRiJC2131
JC2132
RefSeqiNP_000833.1, NM_000842.4 [P41594-2]
NP_001137303.1, NM_001143831.2 [P41594-1]
XP_006718891.1, XM_006718828.3 [P41594-1]
XP_011541094.1, XM_011542792.1 [P41594-1]
XP_016873116.1, XM_017017627.1 [P41594-2]
UniGeneiHs.147361
Hs.616625

Genome annotation databases

EnsembliENST00000305432; ENSP00000305905; ENSG00000168959 [P41594-2]
ENST00000305447; ENSP00000306138; ENSG00000168959 [P41594-1]
ENST00000455756; ENSP00000405690; ENSG00000168959 [P41594-2]
GeneIDi2915
KEGGihsa:2915
UCSCiuc001pcq.4 human [P41594-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS44694.1 [P41594-1]
CCDS8283.1 [P41594-2]
PIRiJC2131
JC2132
RefSeqiNP_000833.1, NM_000842.4 [P41594-2]
NP_001137303.1, NM_001143831.2 [P41594-1]
XP_006718891.1, XM_006718828.3 [P41594-1]
XP_011541094.1, XM_011542792.1 [P41594-1]
XP_016873116.1, XM_017017627.1 [P41594-2]
UniGeneiHs.147361
Hs.616625

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LMKX-ray2.44A/B18-505[»]
4OO9X-ray2.60A569-836[»]
5CGCX-ray3.10A569-836[»]
5CGDX-ray2.60A569-836[»]
ProteinModelPortaliP41594
SMRiP41594
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109172, 8 interactors
IntActiP41594, 5 interactors
STRINGi9606.ENSP00000306138

Chemistry databases

BindingDBiP41594
ChEMBLiCHEMBL3227
DrugBankiDB00659 Acamprosate
DB06060 ADX-48621
DB05070 ADX10059
DB06201 Rufinamide
GuidetoPHARMACOLOGYi293

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP41594
PhosphoSitePlusiP41594

Polymorphism and mutation databases

BioMutaiGRM5
DMDMi1709020

Proteomic databases

PaxDbiP41594
PeptideAtlasiP41594
PRIDEiP41594
ProteomicsDBi55471
55472 [P41594-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305432; ENSP00000305905; ENSG00000168959 [P41594-2]
ENST00000305447; ENSP00000306138; ENSG00000168959 [P41594-1]
ENST00000455756; ENSP00000405690; ENSG00000168959 [P41594-2]
GeneIDi2915
KEGGihsa:2915
UCSCiuc001pcq.4 human [P41594-1]

Organism-specific databases

CTDi2915
DisGeNETi2915
EuPathDBiHostDB:ENSG00000168959.14
GeneCardsiGRM5
HGNCiHGNC:4597 GRM5
MIMi604102 gene
neXtProtiNX_P41594
OpenTargetsiENSG00000168959
PharmGKBiPA28994
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056 Eukaryota
ENOG410XR6W LUCA
GeneTreeiENSGT00760000118884
HOGENOMiHOG000218636
HOVERGENiHBG107965
InParanoidiP41594
KOiK04604
OMAiDLTGCDP
OrthoDBiEOG091G177R
PhylomeDBiP41594
TreeFamiTF313240

Enzyme and pathway databases

ReactomeiR-HSA-416476 G alpha (q) signalling events
R-HSA-420499 Class C/3 (Metabotropic glutamate/pheromone receptors)
R-HSA-6794361 Neurexins and neuroligins
SignaLinkiP41594
SIGNORiP41594

Miscellaneous databases

ChiTaRSiGRM5 human
EvolutionaryTraceiP41594
GenomeRNAii2915
PROiPR:P41594
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168959 Expressed in 113 organ(s), highest expression level in frontal cortex
CleanExiHS_GRM5
ExpressionAtlasiP41594 baseline and differential
GenevisibleiP41594 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiGRM5_HUMAN
AccessioniPrimary (citable) accession number: P41594
Secondary accession number(s): Q6J164
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 1, 1996
Last modified: November 7, 2018
This is version 175 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  5. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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