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 13-FEB-2019, entry version 152. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT gene for 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., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA 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., RA Balijepalli R.C., Setaluri V.; RT "Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium RT channel 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., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT 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 RP OF VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND RP LYS-781, 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- RT rich, and intracellular domains of the metabotropic glutamate receptor RT 6 abolish 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., RA Kamermans M., Prick L., Riemslag F.C., van Schooneveld M.J., RA Kappers A.M., van Genderen M.M.; RT "Genotype and phenotype of 101 Dutch patients with congenital RT stationary 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 CC activity of down-stream effectors, such as adenylate cyclase. CC Signaling inhibits adenylate cyclase activity (By similarity). CC Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. CC Required for normal vision. {ECO:0000250, CC ECO:0000269|PubMed:23452348}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17405131}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17405131}; CC Multi-pass membrane protein {ECO:0000269|PubMed:17405131}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:17405131}; CC Multi-pass membrane protein {ECO:0000269|PubMed:17405131}. Golgi CC apparatus membrane {ECO:0000269|PubMed:17405131}; Multi-pass CC membrane protein {ECO:0000269|PubMed:17405131}. Cell projection, CC dendrite {ECO:0000250}. Note=Subject to trafficking from the CC endoplasmic reticulum to the Golgi apparatus and then to the cell CC 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 CC 1B is an autosomal recessive form associated with a negative CC electroretinogram waveform. Patients are night blind from an early CC age, and when maximally dark-adapted, they could perceive lights CC only with an intensity equal to or slightly dimmer than that CC normally detected by the cone system. ERGs in response to single CC brief flashes of light have clearly detectable a-waves, which are CC derived from photoreceptors, and greatly reduced b-waves, which CC are derived from the second-order inner retinal neurons. ERGs in CC response to sawtooth flickering light indicate a markedly reduced CC on response and a nearly normal OFF response. There is no CC 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}. CC Note=The disease is caused by mutations affecting the gene CC represented in this 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 UniGene; Hs.248131; -. DR ProteinModelPortal; O15303; -. DR SMR; O15303; -. DR BioGrid; 109173; 1. DR STRING; 9606.ENSP00000231188; -. DR BindingDB; O15303; -. DR ChEMBL; CHEMBL4573; -. DR GuidetoPHARMACOLOGY; 294; -. DR iPTMnet; O15303; -. DR PhosphoSitePlus; O15303; -. DR BioMuta; GRM6; -. DR PaxDb; O15303; -. DR PeptideAtlas; O15303; -. DR PRIDE; O15303; -. DR ProteomicsDB; 48571; -. DR DNASU; 2916; -. DR Ensembl; ENST00000231188; ENSP00000231188; ENSG00000113262. DR Ensembl; ENST00000517717; ENSP00000430767; ENSG00000113262. DR Ensembl; ENST00000650031; ENSP00000497110; ENSG00000113262. DR GeneID; 2916; -. DR KEGG; hsa:2916; -. DR UCSC; uc003mjr.4; human. DR CTD; 2916; -. DR DisGeNET; 2916; -. DR EuPathDB; HostDB:ENSG00000113262.14; -. DR GeneCards; GRM6; -. DR H-InvDB; HIX0024983; -. DR HGNC; HGNC:4598; GRM6. DR HPA; HPA014511; -. 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 eggNOG; KOG1056; Eukaryota. DR eggNOG; ENOG410XR6W; LUCA. DR GeneTree; ENSGT00940000153940; -. DR HOGENOM; HOG000218635; -. DR HOVERGEN; HBG107965; -. DR InParanoid; O15303; -. DR KO; K04608; -. DR OMA; AGRACGQ; -. DR OrthoDB; 309052at2759; -. DR PhylomeDB; O15303; -. DR TreeFam; TF313240; -. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors). DR GeneWiki; Metabotropic_glutamate_receptor_6; -. DR GenomeRNAi; 2916; -. DR PRO; PR:O15303; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; ENSG00000113262; Expressed in 83 organ(s), highest expression level in gastrocnemius. DR Genevisible; O15303; HS. 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:0005887; C:integral component of plasma membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0042734; C:presynaptic membrane; 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:0007196; P:adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway; IBA:GO_Central. 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:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0090280; P:positive regulation of calcium ion import; IMP:UniProtKB. DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central. DR Gene3D; 2.10.50.30; -; 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; IPR017978; GPCR_3_C. DR InterPro; IPR017979; GPCR_3_CS. DR InterPro; IPR000162; GPCR_3_mtglu_rcpt. DR InterPro; IPR000112; GPCR_3_mtglu_rcpt_6. DR InterPro; IPR028082; Peripla_BP_I. 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; SSF53822; 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. PE 1: Evidence at protein level; KW Cell membrane; Cell projection; Complete proteome; KW Congenital stationary night blindness; Disease mutation; KW Disulfide bond; Endoplasmic reticulum; G-protein coupled receptor; KW Glycoprotein; Golgi apparatus; Membrane; Polymorphism; Receptor; KW Reference proteome; Sensory transduction; Signal; Transducer; KW Transmembrane; Transmembrane helix; Vision. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 877 Metabotropic glutamate receptor 6. FT /FTId=PRO_0000012934. FT TOPO_DOM 25 585 Extracellular. {ECO:0000255}. FT TRANSMEM 586 608 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 609 622 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 623 643 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 644 654 Extracellular. {ECO:0000255}. FT TRANSMEM 655 673 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 674 697 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 698 718 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 719 748 Extracellular. {ECO:0000255}. FT TRANSMEM 749 770 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 771 783 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 784 806 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 807 819 Extracellular. {ECO:0000255}. FT TRANSMEM 820 845 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 846 877 Cytoplasmic. {ECO:0000255}. FT REGION 175 177 Glutamate binding. {ECO:0000250}. FT BINDING 154 154 Glutamate. {ECO:0000250}. FT BINDING 225 225 Glutamate. {ECO:0000250}. FT BINDING 307 307 Glutamate. {ECO:0000250}. FT BINDING 400 400 Glutamate. {ECO:0000250}. FT CARBOHYD 296 296 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 451 451 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 479 479 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 567 567 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 57 99 {ECO:0000250}. FT DISULFID 244 536 {ECO:0000250}. FT DISULFID 367 383 {ECO:0000250}. FT DISULFID 423 430 {ECO:0000250}. FT DISULFID 518 537 {ECO:0000250}. FT DISULFID 522 540 {ECO:0000250}. FT DISULFID 543 555 {ECO:0000250}. FT DISULFID 558 571 {ECO:0000250}. FT VARIANT 46 46 P -> L (in CSNB1B; abolishes expression FT at the cell membrane; dbSNP:rs62638197). FT {ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:23714322}. FT /FTId=VAR_069817. FT VARIANT 58 58 G -> R (in CSNB1B; abolishes expression FT at the cell membrane; dbSNP:rs62638198). FT {ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:23714322}. FT /FTId=VAR_069818. FT VARIANT 59 59 Q -> P (no effect on location at the cell FT membrane; dbSNP:rs2645329). FT {ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:9215706}. FT /FTId=VAR_059310. FT VARIANT 150 150 G -> S (in CSNB1B; abolishes expression FT at the cell membrane; dbSNP:rs62638202). FT {ECO:0000269|PubMed:15781871, FT ECO:0000269|PubMed:17405131}. FT /FTId=VAR_030756. FT VARIANT 191 191 S -> F (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036195. FT VARIANT 227 227 E -> V (in dbSNP:rs17078898). FT /FTId=VAR_055876. FT VARIANT 236 236 I -> F (in dbSNP:rs17078896). FT /FTId=VAR_055877. FT VARIANT 405 405 I -> T (in CSNB1B; abolishes expression FT at the cell membrane; dbSNP:rs121434304). FT {ECO:0000269|PubMed:17405131}. FT /FTId=VAR_069819. FT VARIANT 522 522 C -> Y (in CSNB1B; abolishes expression FT at the cell membrane; dbSNP:rs62638208). FT {ECO:0000269|PubMed:17405131, FT ECO:0000269|PubMed:23714322}. FT /FTId=VAR_069820. FT VARIANT 712 712 M -> V (in dbSNP:rs17078877). FT /FTId=VAR_055878. FT VARIANT 781 781 E -> K (in CSNB1B; abolishes expression FT at the cell membrane; dbSNP:rs62638625). FT {ECO:0000269|PubMed:15781871, FT ECO:0000269|PubMed:17405131}. FT /FTId=VAR_030757. FT VARIANT 807 807 A -> V (in dbSNP:rs17078874). FT /FTId=VAR_055879. FT VARIANT 817 817 T -> S (in dbSNP:rs17078857). FT /FTId=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 //