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Protein

Metabotropic glutamate receptor 6

Gene

GRM6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • glutamate receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: UniProtKB
  • group III metabotropic glutamate receptor activity Source: GO_Central
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • 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
  • 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
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Sensory transduction, Vision

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113262-MONOMER.
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

HGNCiHGNC:4598. GRM6.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
  • Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication
  • Golgi apparatus membrane 1 Publication; Multi-pass membrane protein 1 Publication
  • Cell projectiondendrite By similarity

  • Note: Subject to trafficking from the endoplasmic reticulum to the Golgi apparatus and then to the cell membrane.

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

GO - Cellular componenti

  • dendrite Source: UniProtKB-SubCell
  • endoplasmic reticulum membrane Source: UniProtKB
  • Golgi membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • new growing cell tip Source: Ensembl
  • plasma membrane Source: Reactome
  • presynaptic membrane Source: GO_Central
Complete GO annotation...

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 rs62638197dbSNPEnsembl.1
Natural variantiVAR_06981858G → R in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638198dbSNPEnsembl.1
Natural variantiVAR_030756150G → S in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638202dbSNPEnsembl.1
Natural variantiVAR_069819405I → T in CSNB1B; abolishes expression at the cell membrane. 1 PublicationCorresponds to variant rs121434304dbSNPEnsembl.1
Natural variantiVAR_069820522C → Y in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638208dbSNPEnsembl.1
Natural variantiVAR_030757781E → K in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638625dbSNPEnsembl.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...)Sequence analysis1
Disulfide bondi367 ↔ 383By similarity
Disulfide bondi423 ↔ 430By similarity
Glycosylationi451N-linked (GlcNAc...)Sequence analysis1
Glycosylationi479N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi518 ↔ 537By similarity
Disulfide bondi522 ↔ 540By similarity
Disulfide bondi543 ↔ 555By similarity
Disulfide bondi558 ↔ 571By similarity
Glycosylationi567N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO15303.
PeptideAtlasiO15303.
PRIDEiO15303.

PTM databases

iPTMnetiO15303.
PhosphoSitePlusiO15303.

Expressioni

Tissue specificityi

Detected in melanocytes.1 Publication

Gene expression databases

BgeeiENSG00000113262.
CleanExiHS_GRM6.
GenevisibleiO15303. HS.

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

InterProiIPR001828. 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.
IPR000112. GPCR_3_mtglu_rcpt_6.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01056. MTABOTROPC6R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]

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 rs62638197dbSNPEnsembl.1
Natural variantiVAR_06981858G → R in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638198dbSNPEnsembl.1
Natural variantiVAR_05931059Q → P No effect on location at the cell membrane. 2 PublicationsCorresponds to variant rs2645329dbSNPEnsembl.1
Natural variantiVAR_030756150G → S in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638202dbSNPEnsembl.1
Natural variantiVAR_036195191S → F in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_055876227E → V.Corresponds to variant rs17078898dbSNPEnsembl.1
Natural variantiVAR_055877236I → F.Corresponds to variant rs17078896dbSNPEnsembl.1
Natural variantiVAR_069819405I → T in CSNB1B; abolishes expression at the cell membrane. 1 PublicationCorresponds to variant rs121434304dbSNPEnsembl.1
Natural variantiVAR_069820522C → Y in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638208dbSNPEnsembl.1
Natural variantiVAR_055878712M → V.Corresponds to variant rs17078877dbSNPEnsembl.1
Natural variantiVAR_030757781E → K in CSNB1B; abolishes expression at the cell membrane. 2 PublicationsCorresponds to variant rs62638625dbSNPEnsembl.1
Natural variantiVAR_055879807A → V.Corresponds to variant rs17078874dbSNPEnsembl.1
Natural variantiVAR_055880817T → S.Corresponds to variant rs17078857dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliO15303.
SMRiO15303.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109173. 1 interactor.
STRINGi9606.ENSP00000231188.

Chemistry databases

BindingDBiO15303.
ChEMBLiCHEMBL4573.
GuidetoPHARMACOLOGYi294.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO15303.
PhosphoSitePlusiO15303.

Polymorphism and mutation databases

BioMutaiGRM6.

Proteomic databases

PaxDbiO15303.
PeptideAtlasiO15303.
PRIDEiO15303.

Protocols and materials databases

DNASUi2916.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2916.
DisGeNETi2916.
GeneCardsiGRM6.
H-InvDBHIX0024983.
HGNCiHGNC:4598. GRM6.
MalaCardsiGRM6.
MIMi257270. phenotype.
604096. gene.
neXtProtiNX_O15303.
OpenTargetsiENSG00000113262.
Orphaneti215. Congenital stationary night blindness.
PharmGKBiPA28995.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiO15303.
KOiK04608.
OMAiYAIKARG.
OrthoDBiEOG091G177R.
PhylomeDBiO15303.
TreeFamiTF313240.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113262-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).

Miscellaneous databases

GeneWikiiMetabotropic_glutamate_receptor_6.
GenomeRNAii2916.
PROiO15303.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113262.
CleanExiHS_GRM6.
GenevisibleiO15303. HS.

Family and domain databases

InterProiIPR001828. 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.
IPR000112. GPCR_3_mtglu_rcpt_6.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01056. MTABOTROPC6R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiGRM6_HUMAN
AccessioniPrimary (citable) accession number: O15303
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: November 2, 2016
This is version 140 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.