ID GRM6_HUMAN Reviewed; 877 AA. AC O15303; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 16-JUN-2009, sequence version 2. DT 24-JAN-2024, entry version 179. DE RecName: Full=Metabotropic glutamate receptor 6; DE Short=mGluR6; DE Flags: Precursor; GN Name=GRM6; Synonyms=GPRC1F, MGLUR6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-59. RX PubMed=9215706; DOI=10.1111/j.1460-9568.1997.tb01477.x; RA Hashimoto T., Inazawa J., Okamoto N., Tagawa Y., Bessho Y., Honda Y., RA Nakanishi S.; RT "The whole nucleotide sequence and chromosomal localization of the gene for RT human metabotropic glutamate receptor subtype 6."; RL Eur. J. Neurosci. 9:1226-1235(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [3] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=23452348; DOI=10.1111/pcmr.12083; RA Devi S., Markandeya Y., Maddodi N., Dhingra A., Vardi N., Balijepalli R.C., RA Setaluri V.; RT "Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel RT function and increases melanin content in human melanocytes."; RL Pigment Cell Melanoma Res. 26:348-356(2013). RN [4] RP VARIANTS CSNB1B SER-150 AND LYS-781. RX PubMed=15781871; DOI=10.1073/pnas.0501233102; RA Dryja T.P., McGee T.L., Berson E.L., Fishman G.A., Sandberg M.A., RA Alexander K.R., Derlacki D.J., Rajagopalan A.S.; RT "Night blindness and abnormal cone electroretinogram ON responses in RT patients with mutations in the GRM6 gene encoding mGluR6."; RL Proc. Natl. Acad. Sci. U.S.A. 102:4884-4889(2005). RN [5] RP VARIANT [LARGE SCALE ANALYSIS] PHE-191. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [6] RP VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781, RP VARIANT PRO-59, CHARACTERIZATION OF VARIANT PRO-59, CHARACTERIZATION OF RP VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781, RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=17405131; DOI=10.1002/humu.20499; RA Zeitz C., Forster U., Neidhardt J., Feil S., Kalin S., Leifert D., RA Flor P.J., Berger W.; RT "Night blindness-associated mutations in the ligand-binding, cysteine-rich, RT and intracellular domains of the metabotropic glutamate receptor 6 abolish RT protein trafficking."; RL Hum. Mutat. 28:771-780(2007). RN [7] RP VARIANTS CSNB1B LEU-46; ARG-58 AND TYR-522. RX PubMed=23714322; DOI=10.1016/j.ophtha.2013.03.002; RA Bijveld M.M., Florijn R.J., Bergen A.A., van den Born L.I., Kamermans M., RA Prick L., Riemslag F.C., van Schooneveld M.J., Kappers A.M., RA van Genderen M.M.; RT "Genotype and phenotype of 101 Dutch patients with congenital stationary RT night blindness."; RL Ophthalmology 120:2072-2081(2013). CC -!- FUNCTION: G-protein coupled receptor for glutamate. Ligand binding CC causes a conformation change that triggers signaling via guanine CC nucleotide-binding proteins (G proteins) and modulates the activity of CC down-stream effectors, such as adenylate cyclase. Signaling inhibits CC adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 CC channel activity and Ca(2+) uptake. Required for normal vision. CC {ECO:0000250, ECO:0000269|PubMed:23452348}. CC -!- SUBUNIT: Homodimer (PubMed:17405131). Interacts with GPR179 (By CC similarity). {ECO:0000250|UniProtKB:Q5NCH9, CC ECO:0000269|PubMed:17405131}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17405131}; CC Multi-pass membrane protein {ECO:0000269|PubMed:17405131}. Endoplasmic CC reticulum membrane {ECO:0000269|PubMed:17405131}; Multi-pass membrane CC protein {ECO:0000269|PubMed:17405131}. Golgi apparatus membrane CC {ECO:0000269|PubMed:17405131}; Multi-pass membrane protein CC {ECO:0000269|PubMed:17405131}. Cell projection, dendrite {ECO:0000250}. CC Note=Subject to trafficking from the endoplasmic reticulum to the Golgi CC apparatus and then to the cell membrane. CC -!- TISSUE SPECIFICITY: Detected in melanocytes. CC {ECO:0000269|PubMed:23452348}. CC -!- DISEASE: Night blindness, congenital stationary, 1B (CSNB1B) CC [MIM:257270]: A non-progressive retinal disorder characterized by CC impaired night vision. Congenital stationary night blindness type 1B is CC an autosomal recessive form associated with a negative CC electroretinogram waveform. Patients are night blind from an early age, CC and when maximally dark-adapted, they could perceive lights only with CC an intensity equal to or slightly dimmer than that normally detected by CC the cone system. ERGs in response to single brief flashes of light have CC clearly detectable a-waves, which are derived from photoreceptors, and CC greatly reduced b-waves, which are derived from the second-order inner CC retinal neurons. ERGs in response to sawtooth flickering light indicate CC a markedly reduced on response and a nearly normal OFF response. There CC is no subjective delay in the perception of suddenly appearing white vs CC black objects on a gray background. {ECO:0000269|PubMed:15781871, CC ECO:0000269|PubMed:17405131, ECO:0000269|PubMed:23714322}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U82083; AAB82068.1; -; Genomic_DNA. DR EMBL; AC104117; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS4442.1; -. DR RefSeq; NP_000834.2; NM_000843.3. DR AlphaFoldDB; O15303; -. DR SMR; O15303; -. DR BioGRID; 109173; 1. DR STRING; 9606.ENSP00000497110; -. DR BindingDB; O15303; -. DR ChEMBL; CHEMBL4573; -. DR DrugCentral; O15303; -. DR GuidetoPHARMACOLOGY; 294; -. DR GlyCosmos; O15303; 4 sites, No reported glycans. DR GlyGen; O15303; 4 sites. DR iPTMnet; O15303; -. DR PhosphoSitePlus; O15303; -. DR BioMuta; GRM6; -. DR MassIVE; O15303; -. DR PaxDb; 9606-ENSP00000231188; -. DR PeptideAtlas; O15303; -. DR ProteomicsDB; 48571; -. DR Antibodypedia; 17632; 394 antibodies from 32 providers. DR DNASU; 2916; -. DR Ensembl; ENST00000231188.9; ENSP00000231188.5; ENSG00000113262.16. DR Ensembl; ENST00000517717.3; ENSP00000430767.1; ENSG00000113262.16. DR Ensembl; ENST00000650031.1; ENSP00000497110.1; ENSG00000113262.16. DR GeneID; 2916; -. DR KEGG; hsa:2916; -. DR MANE-Select; ENST00000517717.3; ENSP00000430767.1; NM_000843.4; NP_000834.2. DR UCSC; uc003mjr.4; human. DR AGR; HGNC:4598; -. DR CTD; 2916; -. DR DisGeNET; 2916; -. DR GeneCards; GRM6; -. DR HGNC; HGNC:4598; GRM6. DR HPA; ENSG00000113262; Tissue enriched (retina). DR MalaCards; GRM6; -. DR MIM; 257270; phenotype. DR MIM; 604096; gene. DR neXtProt; NX_O15303; -. DR OpenTargets; ENSG00000113262; -. DR Orphanet; 215; Congenital stationary night blindness. DR PharmGKB; PA28995; -. DR VEuPathDB; HostDB:ENSG00000113262; -. DR eggNOG; KOG1056; Eukaryota. DR GeneTree; ENSGT01030000234648; -. DR HOGENOM; CLU_005389_0_0_1; -. DR InParanoid; O15303; -. DR OMA; EACPRDM; -. DR OrthoDB; 5388627at2759; -. DR PhylomeDB; O15303; -. DR TreeFam; TF313240; -. DR PathwayCommons; O15303; -. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors). DR SignaLink; O15303; -. DR SIGNOR; O15303; -. DR BioGRID-ORCS; 2916; 5 hits in 1142 CRISPR screens. DR GeneWiki; Metabotropic_glutamate_receptor_6; -. DR GenomeRNAi; 2916; -. DR Pharos; O15303; Tchem. DR PRO; PR:O15303; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O15303; Protein. DR Bgee; ENSG00000113262; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 95 other cell types or tissues. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0035841; C:new growing cell tip; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0001640; F:adenylate cyclase inhibiting G protein-coupled glutamate receptor activity; IBA:GO_Central. DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:UniProtKB. DR GO; GO:0008066; F:glutamate receptor activity; IMP:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:UniProtKB. DR GO; GO:0009584; P:detection of visible light; TAS:ProtInc. DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl. DR GO; GO:1905665; P:positive regulation of calcium ion import across plasma membrane; IMP:UniProtKB. DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR CDD; cd15453; 7tmC_mGluR6; 1. DR CDD; cd06376; PBP1_mGluR_groupIII; 1. DR Gene3D; 3.40.50.2300; -; 2. DR Gene3D; 2.10.50.30; GPCR, family 3, nine cysteines domain; 1. DR InterPro; IPR001828; ANF_lig-bd_rcpt. DR InterPro; IPR000337; GPCR_3. DR InterPro; IPR011500; GPCR_3_9-Cys_dom. DR InterPro; IPR038550; GPCR_3_9-Cys_sf. DR InterPro; IPR000112; GPCR_3__mGluR6. DR InterPro; IPR017978; GPCR_3_C. DR InterPro; IPR017979; GPCR_3_CS. DR InterPro; IPR000162; GPCR_3_mtglu_rcpt. DR InterPro; IPR028082; Peripla_BP_I. DR PANTHER; PTHR24060; METABOTROPIC GLUTAMATE RECEPTOR; 1. DR PANTHER; PTHR24060:SF24; METABOTROPIC GLUTAMATE RECEPTOR 6; 1. DR Pfam; PF00003; 7tm_3; 1. DR Pfam; PF01094; ANF_receptor; 1. DR Pfam; PF07562; NCD3G; 1. DR PRINTS; PR00248; GPCRMGR. DR PRINTS; PR01056; MTABOTROPC6R. DR PRINTS; PR00593; MTABOTROPICR. DR SUPFAM; SSF53822; Periplasmic binding protein-like I; 1. DR PROSITE; PS00979; G_PROTEIN_RECEP_F3_1; 1. DR PROSITE; PS00980; G_PROTEIN_RECEP_F3_2; 1. DR PROSITE; PS00981; G_PROTEIN_RECEP_F3_3; 1. DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1. DR Genevisible; O15303; HS. PE 1: Evidence at protein level; KW Cell membrane; Cell projection; Congenital stationary night blindness; KW Disease variant; Disulfide bond; Endoplasmic reticulum; KW G-protein coupled receptor; Glycoprotein; Golgi apparatus; Membrane; KW Receptor; Reference proteome; Sensory transduction; Signal; Transducer; KW Transmembrane; Transmembrane helix; Vision. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..877 FT /note="Metabotropic glutamate receptor 6" FT /id="PRO_0000012934" FT TOPO_DOM 25..585 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 586..608 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 609..622 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 623..643 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 644..654 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 655..673 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 674..697 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 698..718 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 719..748 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 749..770 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 771..783 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 784..806 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 807..819 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 820..845 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 846..877 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 856..877 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 154 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 175..177 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 225 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 307 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 400 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 451 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 479 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 567 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 57..99 FT /evidence="ECO:0000250" FT DISULFID 244..536 FT /evidence="ECO:0000250" FT DISULFID 367..383 FT /evidence="ECO:0000250" FT DISULFID 423..430 FT /evidence="ECO:0000250" FT DISULFID 518..537 FT /evidence="ECO:0000250" FT DISULFID 522..540 FT /evidence="ECO:0000250" FT DISULFID 543..555 FT /evidence="ECO:0000250" FT DISULFID 558..571 FT /evidence="ECO:0000250" FT VARIANT 46 FT /note="P -> L (in CSNB1B; abolishes expression at the cell FT membrane; dbSNP:rs62638197)" FT /evidence="ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:23714322" FT /id="VAR_069817" FT VARIANT 58 FT /note="G -> R (in CSNB1B; abolishes expression at the cell FT membrane; dbSNP:rs62638198)" FT /evidence="ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:23714322" FT /id="VAR_069818" FT VARIANT 59 FT /note="Q -> P (no effect on location at the cell membrane; FT dbSNP:rs2645329)" FT /evidence="ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:9215706" FT /id="VAR_059310" FT VARIANT 150 FT /note="G -> S (in CSNB1B; abolishes expression at the cell FT membrane; dbSNP:rs62638202)" FT /evidence="ECO:0000269|PubMed:15781871, FT ECO:0000269|PubMed:17405131" FT /id="VAR_030756" FT VARIANT 191 FT /note="S -> F (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036195" FT VARIANT 227 FT /note="E -> V (in dbSNP:rs17078898)" FT /id="VAR_055876" FT VARIANT 236 FT /note="I -> F (in dbSNP:rs17078896)" FT /id="VAR_055877" FT VARIANT 405 FT /note="I -> T (in CSNB1B; abolishes expression at the cell FT membrane; dbSNP:rs121434304)" FT /evidence="ECO:0000269|PubMed:17405131" FT /id="VAR_069819" FT VARIANT 522 FT /note="C -> Y (in CSNB1B; abolishes expression at the cell FT membrane; dbSNP:rs62638208)" FT /evidence="ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:23714322" FT /id="VAR_069820" FT VARIANT 712 FT /note="M -> V (in dbSNP:rs17078877)" FT /id="VAR_055878" FT VARIANT 781 FT /note="E -> K (in CSNB1B; abolishes expression at the cell FT membrane; dbSNP:rs62638625)" FT /evidence="ECO:0000269|PubMed:15781871, FT ECO:0000269|PubMed:17405131" FT /id="VAR_030757" FT VARIANT 807 FT /note="A -> V (in dbSNP:rs17078874)" FT /id="VAR_055879" FT VARIANT 817 FT /note="T -> S (in dbSNP:rs17078857)" FT /id="VAR_055880" SQ 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 //