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Protein

Metabotropic glutamate receptor 6

Gene

GRM6

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, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca2+ uptake. Required for normal vision.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei154GlutamateBy similarity1
Binding sitei225GlutamateBy similarity1
Binding sitei307GlutamateBy similarity1
Binding sitei400GlutamateBy similarity1

GO - Molecular functioni

  • adenylate cyclase inhibiting G-protein coupled glutamate receptor activity Source: Ensembl
  • glutamate receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: GO_Central
  • chemical synaptic transmission Source: Ensembl
  • detection of light stimulus involved in visual perception Source: UniProtKB
  • detection of visible light Source: ProtInc
  • G-protein coupled glutamate receptor signaling pathway Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: Reactome
  • locomotory behavior Source: Ensembl
  • positive regulation of calcium ion import Source: UniProtKB
  • regulation of synaptic transmission, glutamatergic Source: GO_Central
  • retina development in camera-type eye Source: Ensembl

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processSensory transduction, Vision

Enzyme and pathway databases

ReactomeiR-HSA-418594 G alpha (i) signalling events
R-HSA-420499 Class C/3 (Metabotropic glutamate/pheromone receptors)

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 6
Short name:
mGluR6
Gene namesi
Name:GRM6
Synonyms:GPRC1F, MGLUR6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113262.14
HGNCiHGNC:4598 GRM6
MIMi604096 gene
neXtProtiNX_O15303

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 domaini25 – 585ExtracellularSequence analysisAdd BLAST561
Transmembranei586 – 608Helical; Name=1Sequence analysisAdd BLAST23
Topological domaini609 – 622CytoplasmicSequence analysisAdd BLAST14
Transmembranei623 – 643Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini644 – 654ExtracellularSequence analysisAdd BLAST11
Transmembranei655 – 673Helical; Name=3Sequence analysisAdd BLAST19
Topological domaini674 – 697CytoplasmicSequence analysisAdd BLAST24
Transmembranei698 – 718Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini719 – 748ExtracellularSequence analysisAdd BLAST30
Transmembranei749 – 770Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini771 – 783CytoplasmicSequence analysisAdd BLAST13
Transmembranei784 – 806Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini807 – 819ExtracellularSequence analysisAdd BLAST13
Transmembranei820 – 845Helical; Name=7Sequence analysisAdd BLAST26
Topological domaini846 – 877CytoplasmicSequence analysisAdd BLAST32

Keywords - Cellular componenti

Cell membrane, Cell projection, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Night blindness, congenital stationary, 1B (CSNB1B)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA non-progressive retinal disorder characterized by impaired night vision. Congenital stationary night blindness type 1B is an autosomal recessive form associated with a negative electroretinogram waveform. Patients are night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system. ERGs in response to single brief flashes of light have clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicate a markedly reduced on response and a nearly normal OFF response. There is no subjective delay in the perception of suddenly appearing white vs black objects on a gray background.
See also OMIM:257270
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06981746P → L in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638197EnsemblClinVar.1
Natural variantiVAR_06981858G → R in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638198EnsemblClinVar.1
Natural variantiVAR_030756150G → S in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638202EnsemblClinVar.1
Natural variantiVAR_069819405I → T in CSNB1B; abolishes expression at the cell membrane. 1 PublicationCorresponds to variant dbSNP:rs121434304EnsemblClinVar.1
Natural variantiVAR_069820522C → Y in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638208EnsemblClinVar.1
Natural variantiVAR_030757781E → K in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638625EnsemblClinVar.1

Keywords - Diseasei

Congenital stationary night blindness, Disease mutation

Organism-specific databases

DisGeNETi2916
MalaCardsiGRM6
MIMi257270 phenotype
OpenTargetsiENSG00000113262
Orphaneti215 Congenital stationary night blindness
PharmGKBiPA28995

Chemistry databases

ChEMBLiCHEMBL4573
GuidetoPHARMACOLOGYi294

Polymorphism and mutation databases

BioMutaiGRM6

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001293425 – 877Metabotropic glutamate receptor 6Add BLAST853

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi57 ↔ 99By similarity
Disulfide bondi244 ↔ 536By similarity
Glycosylationi296N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi367 ↔ 383By similarity
Disulfide bondi423 ↔ 430By similarity
Glycosylationi451N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi479N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi518 ↔ 537By similarity
Disulfide bondi522 ↔ 540By similarity
Disulfide bondi543 ↔ 555By similarity
Disulfide bondi558 ↔ 571By similarity
Glycosylationi567N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO15303
PeptideAtlasiO15303
PRIDEiO15303
ProteomicsDBi48571

PTM databases

iPTMnetiO15303
PhosphoSitePlusiO15303

Expressioni

Tissue specificityi

Detected in melanocytes.1 Publication

Gene expression databases

BgeeiENSG00000113262
CleanExiHS_GRM6
GenevisibleiO15303 HS

Organism-specific databases

HPAiHPA014511

Interactioni

Subunit structurei

Homodimer.1 Publication

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi109173, 1 interactor
STRINGi9606.ENSP00000231188

Chemistry databases

BindingDBiO15303

Structurei

3D structure databases

ProteinModelPortaliO15303
SMRiO15303
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 177Glutamate bindingBy similarity3

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056 Eukaryota
ENOG410XR6W LUCA
GeneTreeiENSGT00760000118884
HOGENOMiHOG000218635
HOVERGENiHBG107965
InParanoidiO15303
KOiK04608
OMAiYAIKARG
OrthoDBiEOG091G177R
PhylomeDBiO15303
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
IPR000112 GPCR_3_mtglu_rcpt_6
IPR028082 Peripla_BP_I
PfamiView protein in Pfam
PF00003 7tm_3, 1 hit
PF01094 ANF_receptor, 1 hit
PF07562 NCD3G, 1 hit
PRINTSiPR00248 GPCRMGR
PR01056 MTABOTROPC6R
PR00593 MTABOTROPICR
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

Sequencei

Sequence statusi: Complete.

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

O15303-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARPRRAREP LLVALLPLAW LAQAGLARAA GSVRLAGGLT LGGLFPVHAR
60 70 80 90 100
GAAGRACGQL KKEQGVHRLE AMLYALDRVN ADPELLPGVR LGARLLDTCS
110 120 130 140 150
RDTYALEQAL SFVQALIRGR GDGDEVGVRC PGGVPPLRPA PPERVVAVVG
160 170 180 190 200
ASASSVSIMV ANVLRLFAIP QISYASTAPE LSDSTRYDFF SRVVPPDSYQ
210 220 230 240 250
AQAMVDIVRA LGWNYVSTLA SEGNYGESGV EAFVQISREA GGVCIAQSIK
260 270 280 290 300
IPREPKPGEF SKVIRRLMET PNARGIIIFA NEDDIRRVLE AARQANLTGH
310 320 330 340 350
FLWVGSDSWG AKTSPILSLE DVAVGAITIL PKRASIDGFD QYFMTRSLEN
360 370 380 390 400
NRRNIWFAEF WEENFNCKLT SSGTQSDDST RKCTGEERIG RDSTYEQEGK
410 420 430 440 450
VQFVIDAVYA IAHALHSMHQ ALCPGHTGLC PAMEPTDGRM LLQYIRAVRF
460 470 480 490 500
NGSAGTPVMF NENGDAPGRY DIFQYQATNG SASSGGYQAV GQWAETLRLD
510 520 530 540 550
VEALQWSGDP HEVPSSLCSL PCGPGERKKM VKGVPCCWHC EACDGYRFQV
560 570 580 590 600
DEFTCEACPG DMRPTPNHTG CRPTPVVRLS WSSPWAAPPL LLAVLGIVAT
610 620 630 640 650
TTVVATFVRY NNTPIVRASG RELSYVLLTG IFLIYAITFL MVAEPGAAVC
660 670 680 690 700
AARRLFLGLG TTLSYSALLT KTNRIYRIFE QGKRSVTPPP FISPTSQLVI
710 720 730 740 750
TFSLTSLQVV GMIAWLGARP PHSVIDYEEQ RTVDPEQARG VLKCDMSDLS
760 770 780 790 800
LIGCLGYSLL LMVTCTVYAI KARGVPETFN EAKPIGFTMY TTCIIWLAFV
810 820 830 840 850
PIFFGTAQSA EKIYIQTTTL TVSLSLSASV SLGMLYVPKT YVILFHPEQN
860 870
VQKRKRSLKA TSTVAAPPKG EDAEAHK
Length:877
Mass (Da):95,468
Last modified:June 16, 2009 - v2
Checksum:i2AB27C5627B388C6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06981746P → L in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638197EnsemblClinVar.1
Natural variantiVAR_06981858G → R in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638198EnsemblClinVar.1
Natural variantiVAR_05931059Q → P No effect on location at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs2645329EnsemblClinVar.1
Natural variantiVAR_030756150G → S in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638202EnsemblClinVar.1
Natural variantiVAR_036195191S → F in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_055876227E → V. Corresponds to variant dbSNP:rs17078898Ensembl.1
Natural variantiVAR_055877236I → F. Corresponds to variant dbSNP:rs17078896Ensembl.1
Natural variantiVAR_069819405I → T in CSNB1B; abolishes expression at the cell membrane. 1 PublicationCorresponds to variant dbSNP:rs121434304EnsemblClinVar.1
Natural variantiVAR_069820522C → Y in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638208EnsemblClinVar.1
Natural variantiVAR_055878712M → V. Corresponds to variant dbSNP:rs17078877EnsemblClinVar.1
Natural variantiVAR_030757781E → K in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs62638625EnsemblClinVar.1
Natural variantiVAR_055879807A → V. Corresponds to variant dbSNP:rs17078874EnsemblClinVar.1
Natural variantiVAR_055880817T → S. Corresponds to variant dbSNP:rs17078857Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82083 Genomic DNA Translation: AAB82068.1
AC104117 Genomic DNA No translation available.
CCDSiCCDS4442.1
RefSeqiNP_000834.2, NM_000843.3
UniGeneiHs.248131

Genome annotation databases

EnsembliENST00000231188; ENSP00000231188; ENSG00000113262
ENST00000517717; ENSP00000430767; ENSG00000113262
GeneIDi2916
KEGGihsa:2916
UCSCiuc003mjr.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGRM6_HUMAN
AccessioniPrimary (citable) accession number: O15303
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: June 20, 2018
This is version 147 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

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