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O15303 (GRM6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metabotropic glutamate receptor 6

Short name=mGluR6
Gene names
Name:GRM6
Synonyms:GPRC1F, MGLUR6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length877 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, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity By similarity. Signaling stimulates TRPM1 channel activity and Ca2+ uptake. Required for normal vision. Ref.3

Subunit structure

Homodimer. Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cell projectiondendrite By similarity. Note: Subject to trafficking from the endoplasmic reticulum to the Golgi apparatus and then to the cell membrane. Ref.6

Tissue specificity

Detected in melanocytes. Ref.3

Involvement in disease

Night blindness, congenital stationary, 1B (CSNB1B) [MIM:257270]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.6 Ref.7

Sequence similarities

Belongs to the G-protein coupled receptor 3 family.

Ontologies

Keywords
   Biological processSensory transduction
Vision
   Cellular componentCell membrane
Cell projection
Endoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DiseaseCongenital stationary night blindness
Disease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled glutamate receptor signaling pathway

Inferred from mutant phenotype Ref.3. Source: UniProtKB

detection of light stimulus involved in visual perception

Inferred from mutant phenotype Ref.6. Source: UniProtKB

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

positive regulation of calcium ion import

Inferred from mutant phenotype Ref.3. Source: UniProtKB

retina development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi membrane

Inferred from direct assay Ref.6. Source: UniProtKB

dendrite

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum membrane

Inferred from direct assay Ref.6. Source: UniProtKB

integral component of plasma membrane

Inferred from direct assay Ref.6. Source: UniProtKB

new growing cell tip

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionG-protein coupled receptor activity

Traceable author statement Ref.1. Source: UniProtKB

adenylate cyclase inhibiting G-protein coupled glutamate receptor activity

Inferred from electronic annotation. Source: Ensembl

glutamate receptor activity

Inferred from mutant phenotype Ref.3. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 877853Metabotropic glutamate receptor 6
PRO_0000012934

Regions

Topological domain25 – 585561Extracellular Potential
Transmembrane586 – 60823Helical; Name=1; Potential
Topological domain609 – 62214Cytoplasmic Potential
Transmembrane623 – 64321Helical; Name=2; Potential
Topological domain644 – 65411Extracellular Potential
Transmembrane655 – 67319Helical; Name=3; Potential
Topological domain674 – 69724Cytoplasmic Potential
Transmembrane698 – 71821Helical; Name=4; Potential
Topological domain719 – 74830Extracellular Potential
Transmembrane749 – 77022Helical; Name=5; Potential
Topological domain771 – 78313Cytoplasmic Potential
Transmembrane784 – 80623Helical; Name=6; Potential
Topological domain807 – 81913Extracellular Potential
Transmembrane820 – 84526Helical; Name=7; Potential
Topological domain846 – 87732Cytoplasmic Potential
Region175 – 1773Glutamate binding By similarity

Sites

Binding site1541Glutamate By similarity
Binding site2251Glutamate By similarity
Binding site3071Glutamate By similarity
Binding site4001Glutamate By similarity

Amino acid modifications

Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation4511N-linked (GlcNAc...) Potential
Glycosylation4791N-linked (GlcNAc...) Potential
Glycosylation5671N-linked (GlcNAc...) Potential
Disulfide bond57 ↔ 99 By similarity
Disulfide bond244 ↔ 536 By similarity
Disulfide bond367 ↔ 383 By similarity
Disulfide bond423 ↔ 430 By similarity
Disulfide bond518 ↔ 537 By similarity
Disulfide bond522 ↔ 540 By similarity
Disulfide bond543 ↔ 555 By similarity
Disulfide bond558 ↔ 571 By similarity

Natural variations

Natural variant461P → L in CSNB1B; abolishes expression at the cell membrane. Ref.6 Ref.7
VAR_069817
Natural variant581G → R in CSNB1B; abolishes expression at the cell membrane. Ref.6 Ref.7
VAR_069818
Natural variant591Q → P No effect on location at the cell membrane. Ref.1 Ref.6
Corresponds to variant rs2645329 [ dbSNP | Ensembl ].
VAR_059310
Natural variant1501G → S in CSNB1B; abolishes expression at the cell membrane. Ref.4 Ref.6
VAR_030756
Natural variant1911S → F in a breast cancer sample; somatic mutation. Ref.5
VAR_036195
Natural variant2271E → V.
Corresponds to variant rs17078898 [ dbSNP | Ensembl ].
VAR_055876
Natural variant2361I → F.
Corresponds to variant rs17078896 [ dbSNP | Ensembl ].
VAR_055877
Natural variant4051I → T in CSNB1B; abolishes expression at the cell membrane. Ref.6
VAR_069819
Natural variant5221C → Y in CSNB1B; abolishes expression at the cell membrane. Ref.6 Ref.7
VAR_069820
Natural variant7121M → V.
Corresponds to variant rs17078877 [ dbSNP | Ensembl ].
VAR_055878
Natural variant7811E → K in CSNB1B; abolishes expression at the cell membrane. Ref.4 Ref.6
VAR_030757
Natural variant8071A → V.
Corresponds to variant rs17078874 [ dbSNP | Ensembl ].
VAR_055879
Natural variant8171T → S.
Corresponds to variant rs17078857 [ dbSNP | Ensembl ].
VAR_055880

Sequences

Sequence LengthMass (Da)Tools
O15303 [UniParc].

Last modified June 16, 2009. Version 2.
Checksum: 2AB27C5627B388C6

FASTA87795,468
        10         20         30         40         50         60 
MARPRRAREP LLVALLPLAW LAQAGLARAA GSVRLAGGLT LGGLFPVHAR GAAGRACGQL 

        70         80         90        100        110        120 
KKEQGVHRLE AMLYALDRVN ADPELLPGVR LGARLLDTCS RDTYALEQAL SFVQALIRGR 

       130        140        150        160        170        180 
GDGDEVGVRC PGGVPPLRPA PPERVVAVVG ASASSVSIMV ANVLRLFAIP QISYASTAPE 

       190        200        210        220        230        240 
LSDSTRYDFF SRVVPPDSYQ AQAMVDIVRA LGWNYVSTLA SEGNYGESGV EAFVQISREA 

       250        260        270        280        290        300 
GGVCIAQSIK IPREPKPGEF SKVIRRLMET PNARGIIIFA NEDDIRRVLE AARQANLTGH 

       310        320        330        340        350        360 
FLWVGSDSWG AKTSPILSLE DVAVGAITIL PKRASIDGFD QYFMTRSLEN NRRNIWFAEF 

       370        380        390        400        410        420 
WEENFNCKLT SSGTQSDDST RKCTGEERIG RDSTYEQEGK VQFVIDAVYA IAHALHSMHQ 

       430        440        450        460        470        480 
ALCPGHTGLC PAMEPTDGRM LLQYIRAVRF NGSAGTPVMF NENGDAPGRY DIFQYQATNG 

       490        500        510        520        530        540 
SASSGGYQAV GQWAETLRLD VEALQWSGDP HEVPSSLCSL PCGPGERKKM VKGVPCCWHC 

       550        560        570        580        590        600 
EACDGYRFQV DEFTCEACPG DMRPTPNHTG CRPTPVVRLS WSSPWAAPPL LLAVLGIVAT 

       610        620        630        640        650        660 
TTVVATFVRY NNTPIVRASG RELSYVLLTG IFLIYAITFL MVAEPGAAVC AARRLFLGLG 

       670        680        690        700        710        720 
TTLSYSALLT KTNRIYRIFE QGKRSVTPPP FISPTSQLVI TFSLTSLQVV GMIAWLGARP 

       730        740        750        760        770        780 
PHSVIDYEEQ RTVDPEQARG VLKCDMSDLS LIGCLGYSLL LMVTCTVYAI KARGVPETFN 

       790        800        810        820        830        840 
EAKPIGFTMY TTCIIWLAFV PIFFGTAQSA EKIYIQTTTL TVSLSLSASV SLGMLYVPKT 

       850        860        870 
YVILFHPEQN VQKRKRSLKA TSTVAAPPKG EDAEAHK 

« Hide

References

« Hide 'large scale' references
[1]"The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6."
Hashimoto T., Inazawa J., Okamoto N., Tagawa Y., Bessho Y., Honda Y., Nakanishi S.
Eur. J. Neurosci. 9:1226-1235(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-59.
[2]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes."
Devi S., Markandeya Y., Maddodi N., Dhingra A., Vardi N., Balijepalli R.C., Setaluri V.
Pigment Cell Melanoma Res. 26:348-356(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[4]"Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6."
Dryja T.P., McGee T.L., Berson E.L., Fishman G.A., Sandberg M.A., Alexander K.R., Derlacki D.J., Rajagopalan A.S.
Proc. Natl. Acad. Sci. U.S.A. 102:4884-4889(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CSNB1B SER-150 AND LYS-781.
[5]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-191.
[6]"Night blindness-associated mutations in the ligand-binding, cysteine-rich, and intracellular domains of the metabotropic glutamate receptor 6 abolish protein trafficking."
Zeitz C., Forster U., Neidhardt J., Feil S., Kalin S., Leifert D., Flor P.J., Berger W.
Hum. Mutat. 28:771-780(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781, VARIANT PRO-59, CHARACTERIZATION OF VARIANT PRO-59, CHARACTERIZATION OF VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781, SUBUNIT, SUBCELLULAR LOCATION.
[7]"Genotype and phenotype of 101 Dutch patients with congenital stationary night blindness."
Bijveld M.M., Florijn R.J., Bergen A.A., van den Born L.I., Kamermans M., Prick L., Riemslag F.C., van Schooneveld M.J., Kappers A.M., van Genderen M.M.
Ophthalmology 120:2072-2081(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CSNB1B LEU-46; ARG-58 AND TYR-522.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U82083 Genomic DNA. Translation: AAB82068.1.
AC104117 Genomic DNA. No translation available.
RefSeqNP_000834.2. NM_000843.3.
UniGeneHs.248131.

3D structure databases

ProteinModelPortalO15303.
SMRO15303. Positions 32-575.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000231188.

Chemistry

BindingDBO15303.
ChEMBLCHEMBL4573.
GuidetoPHARMACOLOGY294.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteO15303.

Proteomic databases

PaxDbO15303.
PRIDEO15303.

Protocols and materials databases

DNASU2916.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000231188; ENSP00000231188; ENSG00000113262.
ENST00000517717; ENSP00000430767; ENSG00000113262.
GeneID2916.
KEGGhsa:2916.
UCSCuc003mjr.3. human.

Organism-specific databases

CTD2916.
GeneCardsGC05M178392.
H-InvDBHIX0024983.
HGNCHGNC:4598. GRM6.
MIM257270. phenotype.
604096. gene.
neXtProtNX_O15303.
Orphanet215. Congenital stationary night blindness.
PharmGKBPA28995.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295200.
HOGENOMHOG000218635.
HOVERGENHBG107965.
KOK04608.
OMAVCIAQSI.
OrthoDBEOG7Z0JXG.
TreeFamTF313240.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeO15303.
CleanExHS_GRM6.
GenevestigatorO15303.

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.
IPR000112. GPCR_3_mtglu_rcpt_6.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSPR00248. GPCRMGR.
PR01056. MTABOTROPC6R.
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

GeneWikiMetabotropic_glutamate_receptor_6.
GenomeRNAi2916.
NextBio11559.
PROO15303.
SOURCESearch...

Entry information

Entry nameGRM6_HUMAN
AccessionPrimary (citable) accession number: O15303
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: February 19, 2014
This is version 117 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries