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Metabotropic glutamate receptor 6 (mGluR6)

 GRM6_HUMAN              Reviewed;         877 AA.
O15303;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
16-JUN-2009, sequence version 2.
12-SEP-2018, entry version 148.
RecName: Full=Metabotropic glutamate receptor 6;
Short=mGluR6;
Flags: Precursor;
Name=GRM6; Synonyms=GPRC1F, MGLUR6;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-59.
PubMed=9215706; DOI=10.1111/j.1460-9568.1997.tb01477.x;
Hashimoto T., Inazawa J., Okamoto N., Tagawa Y., Bessho Y., Honda Y.,
Nakanishi S.;
"The whole nucleotide sequence and chromosomal localization of the
gene for human metabotropic glutamate receptor subtype 6.";
Eur. J. Neurosci. 9:1226-1235(1997).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15372022; DOI=10.1038/nature02919;
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.,
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.;
"The DNA sequence and comparative analysis of human chromosome 5.";
Nature 431:268-274(2004).
[3]
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=23452348; DOI=10.1111/pcmr.12083;
Devi S., Markandeya Y., Maddodi N., Dhingra A., Vardi N.,
Balijepalli R.C., Setaluri V.;
"Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium
channel function and increases melanin content in human melanocytes.";
Pigment Cell Melanoma Res. 26:348-356(2013).
[4]
VARIANTS CSNB1B SER-150 AND LYS-781.
PubMed=15781871; DOI=10.1073/pnas.0501233102;
Dryja T.P., McGee T.L., Berson E.L., Fishman G.A., Sandberg M.A.,
Alexander K.R., Derlacki D.J., Rajagopalan A.S.;
"Night blindness and abnormal cone electroretinogram ON responses in
patients with mutations in the GRM6 gene encoding mGluR6.";
Proc. Natl. Acad. Sci. U.S.A. 102:4884-4889(2005).
[5]
VARIANT [LARGE SCALE ANALYSIS] PHE-191.
PubMed=16959974; DOI=10.1126/science.1133427;
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., 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.;
"The consensus coding sequences of human breast and colorectal
cancers.";
Science 314:268-274(2006).
[6]
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, AND SUBCELLULAR LOCATION.
PubMed=17405131; DOI=10.1002/humu.20499;
Zeitz C., Forster U., Neidhardt J., Feil S., Kalin S., Leifert D.,
Flor P.J., Berger W.;
"Night blindness-associated mutations in the ligand-binding, cysteine-
rich, and intracellular domains of the metabotropic glutamate receptor
6 abolish protein trafficking.";
Hum. Mutat. 28:771-780(2007).
[7]
VARIANTS CSNB1B LEU-46; ARG-58 AND TYR-522.
PubMed=23714322; DOI=10.1016/j.ophtha.2013.03.002;
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.;
"Genotype and phenotype of 101 Dutch patients with congenital
stationary night blindness.";
Ophthalmology 120:2072-2081(2013).
-!- 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 Ca(2+) uptake.
Required for normal vision. {ECO:0000250,
ECO:0000269|PubMed:23452348}.
-!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17405131}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17405131};
Multi-pass membrane protein {ECO:0000269|PubMed:17405131}.
Endoplasmic reticulum membrane {ECO:0000269|PubMed:17405131};
Multi-pass membrane protein {ECO:0000269|PubMed:17405131}. Golgi
apparatus membrane {ECO:0000269|PubMed:17405131}; Multi-pass
membrane protein {ECO:0000269|PubMed:17405131}. Cell projection,
dendrite {ECO:0000250}. Note=Subject to trafficking from the
endoplasmic reticulum to the Golgi apparatus and then to the cell
membrane.
-!- TISSUE SPECIFICITY: Detected in melanocytes.
{ECO:0000269|PubMed:23452348}.
-!- 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. {ECO:0000269|PubMed:15781871,
ECO:0000269|PubMed:17405131, ECO:0000269|PubMed:23714322}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
{ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; U82083; AAB82068.1; -; Genomic_DNA.
EMBL; AC104117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
CCDS; CCDS4442.1; -.
RefSeq; NP_000834.2; NM_000843.3.
UniGene; Hs.248131; -.
ProteinModelPortal; O15303; -.
SMR; O15303; -.
BioGrid; 109173; 1.
STRING; 9606.ENSP00000231188; -.
BindingDB; O15303; -.
ChEMBL; CHEMBL4573; -.
GuidetoPHARMACOLOGY; 294; -.
iPTMnet; O15303; -.
PhosphoSitePlus; O15303; -.
BioMuta; GRM6; -.
PaxDb; O15303; -.
PeptideAtlas; O15303; -.
PRIDE; O15303; -.
ProteomicsDB; 48571; -.
DNASU; 2916; -.
Ensembl; ENST00000231188; ENSP00000231188; ENSG00000113262.
Ensembl; ENST00000517717; ENSP00000430767; ENSG00000113262.
GeneID; 2916; -.
KEGG; hsa:2916; -.
UCSC; uc003mjr.4; human.
CTD; 2916; -.
DisGeNET; 2916; -.
EuPathDB; HostDB:ENSG00000113262.14; -.
GeneCards; GRM6; -.
H-InvDB; HIX0024983; -.
HGNC; HGNC:4598; GRM6.
HPA; HPA014511; -.
MalaCards; GRM6; -.
MIM; 257270; phenotype.
MIM; 604096; gene.
neXtProt; NX_O15303; -.
OpenTargets; ENSG00000113262; -.
Orphanet; 215; Congenital stationary night blindness.
PharmGKB; PA28995; -.
eggNOG; KOG1056; Eukaryota.
eggNOG; ENOG410XR6W; LUCA.
GeneTree; ENSGT00760000118884; -.
HOGENOM; HOG000218635; -.
HOVERGEN; HBG107965; -.
InParanoid; O15303; -.
KO; K04608; -.
OMA; YAIKARG; -.
OrthoDB; EOG091G177R; -.
PhylomeDB; O15303; -.
TreeFam; TF313240; -.
Reactome; R-HSA-418594; G alpha (i) signalling events.
Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
GeneWiki; Metabotropic_glutamate_receptor_6; -.
GenomeRNAi; 2916; -.
PRO; PR:O15303; -.
Proteomes; UP000005640; Chromosome 5.
Bgee; ENSG00000113262; Expressed in 83 organ(s), highest expression level in gastrocnemius.
CleanEx; HS_GRM6; -.
Genevisible; O15303; HS.
GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
GO; GO:0035841; C:new growing cell tip; IEA:Ensembl.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
GO; GO:0001640; F:adenylate cyclase inhibiting G-protein coupled glutamate receptor activity; IEA:Ensembl.
GO; GO:0004930; F:G-protein coupled receptor activity; TAS:UniProtKB.
GO; GO:0008066; F:glutamate receptor activity; IMP:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
GO; GO:0007196; P:adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway; IBA:GO_Central.
GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl.
GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:UniProtKB.
GO; GO:0009584; P:detection of visible light; TAS:ProtInc.
GO; GO:0007216; P:G-protein coupled glutamate receptor signaling pathway; IMP:UniProtKB.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:Reactome.
GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
GO; GO:0090280; P:positive regulation of calcium ion import; IMP:UniProtKB.
GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
Gene3D; 2.10.50.30; -; 1.
InterPro; IPR001828; ANF_lig-bd_rcpt.
InterPro; IPR000337; GPCR_3.
InterPro; IPR011500; GPCR_3_9-Cys_dom.
InterPro; IPR038550; GPCR_3_9-Cys_sf.
InterPro; IPR017978; GPCR_3_C.
InterPro; IPR017979; GPCR_3_CS.
InterPro; IPR000162; GPCR_3_mtglu_rcpt.
InterPro; IPR000112; GPCR_3_mtglu_rcpt_6.
InterPro; IPR028082; Peripla_BP_I.
Pfam; PF00003; 7tm_3; 1.
Pfam; PF01094; ANF_receptor; 1.
Pfam; PF07562; NCD3G; 1.
PRINTS; PR00248; GPCRMGR.
PRINTS; PR01056; MTABOTROPC6R.
PRINTS; PR00593; MTABOTROPICR.
SUPFAM; SSF53822; SSF53822; 1.
PROSITE; PS00979; G_PROTEIN_RECEP_F3_1; 1.
PROSITE; PS00980; G_PROTEIN_RECEP_F3_2; 1.
PROSITE; PS00981; G_PROTEIN_RECEP_F3_3; 1.
PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1.
1: Evidence at protein level;
Cell membrane; Cell projection; Complete proteome;
Congenital stationary night blindness; Disease mutation;
Disulfide bond; Endoplasmic reticulum; G-protein coupled receptor;
Glycoprotein; Golgi apparatus; Membrane; Polymorphism; Receptor;
Reference proteome; Sensory transduction; Signal; Transducer;
Transmembrane; Transmembrane helix; Vision.
SIGNAL 1 24 {ECO:0000255}.
CHAIN 25 877 Metabotropic glutamate receptor 6.
/FTId=PRO_0000012934.
TOPO_DOM 25 585 Extracellular. {ECO:0000255}.
TRANSMEM 586 608 Helical; Name=1. {ECO:0000255}.
TOPO_DOM 609 622 Cytoplasmic. {ECO:0000255}.
TRANSMEM 623 643 Helical; Name=2. {ECO:0000255}.
TOPO_DOM 644 654 Extracellular. {ECO:0000255}.
TRANSMEM 655 673 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 674 697 Cytoplasmic. {ECO:0000255}.
TRANSMEM 698 718 Helical; Name=4. {ECO:0000255}.
TOPO_DOM 719 748 Extracellular. {ECO:0000255}.
TRANSMEM 749 770 Helical; Name=5. {ECO:0000255}.
TOPO_DOM 771 783 Cytoplasmic. {ECO:0000255}.
TRANSMEM 784 806 Helical; Name=6. {ECO:0000255}.
TOPO_DOM 807 819 Extracellular. {ECO:0000255}.
TRANSMEM 820 845 Helical; Name=7. {ECO:0000255}.
TOPO_DOM 846 877 Cytoplasmic. {ECO:0000255}.
REGION 175 177 Glutamate binding. {ECO:0000250}.
BINDING 154 154 Glutamate. {ECO:0000250}.
BINDING 225 225 Glutamate. {ECO:0000250}.
BINDING 307 307 Glutamate. {ECO:0000250}.
BINDING 400 400 Glutamate. {ECO:0000250}.
CARBOHYD 296 296 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 451 451 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 479 479 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 567 567 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 57 99 {ECO:0000250}.
DISULFID 244 536 {ECO:0000250}.
DISULFID 367 383 {ECO:0000250}.
DISULFID 423 430 {ECO:0000250}.
DISULFID 518 537 {ECO:0000250}.
DISULFID 522 540 {ECO:0000250}.
DISULFID 543 555 {ECO:0000250}.
DISULFID 558 571 {ECO:0000250}.
VARIANT 46 46 P -> L (in CSNB1B; abolishes expression
at the cell membrane; dbSNP:rs62638197).
{ECO:0000269|PubMed:17405131,
ECO:0000269|PubMed:23714322}.
/FTId=VAR_069817.
VARIANT 58 58 G -> R (in CSNB1B; abolishes expression
at the cell membrane; dbSNP:rs62638198).
{ECO:0000269|PubMed:17405131,
ECO:0000269|PubMed:23714322}.
/FTId=VAR_069818.
VARIANT 59 59 Q -> P (no effect on location at the cell
membrane; dbSNP:rs2645329).
{ECO:0000269|PubMed:17405131,
ECO:0000269|PubMed:9215706}.
/FTId=VAR_059310.
VARIANT 150 150 G -> S (in CSNB1B; abolishes expression
at the cell membrane; dbSNP:rs62638202).
{ECO:0000269|PubMed:15781871,
ECO:0000269|PubMed:17405131}.
/FTId=VAR_030756.
VARIANT 191 191 S -> F (in a breast cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036195.
VARIANT 227 227 E -> V (in dbSNP:rs17078898).
/FTId=VAR_055876.
VARIANT 236 236 I -> F (in dbSNP:rs17078896).
/FTId=VAR_055877.
VARIANT 405 405 I -> T (in CSNB1B; abolishes expression
at the cell membrane; dbSNP:rs121434304).
{ECO:0000269|PubMed:17405131}.
/FTId=VAR_069819.
VARIANT 522 522 C -> Y (in CSNB1B; abolishes expression
at the cell membrane; dbSNP:rs62638208).
{ECO:0000269|PubMed:17405131,
ECO:0000269|PubMed:23714322}.
/FTId=VAR_069820.
VARIANT 712 712 M -> V (in dbSNP:rs17078877).
/FTId=VAR_055878.
VARIANT 781 781 E -> K (in CSNB1B; abolishes expression
at the cell membrane; dbSNP:rs62638625).
{ECO:0000269|PubMed:15781871,
ECO:0000269|PubMed:17405131}.
/FTId=VAR_030757.
VARIANT 807 807 A -> V (in dbSNP:rs17078874).
/FTId=VAR_055879.
VARIANT 817 817 T -> S (in dbSNP:rs17078857).
/FTId=VAR_055880.
SEQUENCE 877 AA; 95468 MW; 2AB27C5627B388C6 CRC64;
MARPRRAREP LLVALLPLAW LAQAGLARAA GSVRLAGGLT LGGLFPVHAR GAAGRACGQL
KKEQGVHRLE AMLYALDRVN ADPELLPGVR LGARLLDTCS RDTYALEQAL SFVQALIRGR
GDGDEVGVRC PGGVPPLRPA PPERVVAVVG ASASSVSIMV ANVLRLFAIP QISYASTAPE
LSDSTRYDFF SRVVPPDSYQ AQAMVDIVRA LGWNYVSTLA SEGNYGESGV EAFVQISREA
GGVCIAQSIK IPREPKPGEF SKVIRRLMET PNARGIIIFA NEDDIRRVLE AARQANLTGH
FLWVGSDSWG AKTSPILSLE DVAVGAITIL PKRASIDGFD QYFMTRSLEN NRRNIWFAEF
WEENFNCKLT SSGTQSDDST RKCTGEERIG RDSTYEQEGK VQFVIDAVYA IAHALHSMHQ
ALCPGHTGLC PAMEPTDGRM LLQYIRAVRF NGSAGTPVMF NENGDAPGRY DIFQYQATNG
SASSGGYQAV GQWAETLRLD VEALQWSGDP HEVPSSLCSL PCGPGERKKM VKGVPCCWHC
EACDGYRFQV DEFTCEACPG DMRPTPNHTG CRPTPVVRLS WSSPWAAPPL LLAVLGIVAT
TTVVATFVRY NNTPIVRASG RELSYVLLTG IFLIYAITFL MVAEPGAAVC AARRLFLGLG
TTLSYSALLT KTNRIYRIFE QGKRSVTPPP FISPTSQLVI TFSLTSLQVV GMIAWLGARP
PHSVIDYEEQ RTVDPEQARG VLKCDMSDLS LIGCLGYSLL LMVTCTVYAI KARGVPETFN
EAKPIGFTMY TTCIIWLAFV PIFFGTAQSA EKIYIQTTTL TVSLSLSASV SLGMLYVPKT
YVILFHPEQN VQKRKRSLKA TSTVAAPPKG EDAEAHK


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