O15303 (GRM6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metabotropic glutamate receptor 6
Short name=mGluR6

Gene names

Name:	GRM6
Synonyms:	GPRC1F, MGLUR6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	877 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for glutamate. The activity of this receptor is mediated by a G-protein that inhibits adenylate cyclase activity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Involvement in disease	Defects in GRM6 are the cause of congenital stationary night blindness type 1B (CSNB1B) [MIM:257270]. This disorder consits of a previously unrecognized, autosomal recessive form of congenital night blindness 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. Ref.3
Sequence similarities	Belongs to the G-protein coupled receptor 3 family.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital stationary night blindness Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	detection of visible light Traceable author statement. Source: ProtInc visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 877	853	Metabotropic glutamate receptor 6		PRO_0000012934
Regions
	Topological domain	25 – 585	561	Extracellular Potential
	Transmembrane	586 – 608	23	Helical; Name=1; Potential
	Topological domain	609 – 622	14	Cytoplasmic Potential
	Transmembrane	623 – 643	21	Helical; Name=2; Potential
	Topological domain	644 – 654	11	Extracellular Potential
	Transmembrane	655 – 673	19	Helical; Name=3; Potential
	Topological domain	674 – 697	24	Cytoplasmic Potential
	Transmembrane	698 – 718	21	Helical; Name=4; Potential
	Topological domain	719 – 748	30	Extracellular Potential
	Transmembrane	749 – 770	22	Helical; Name=5; Potential
	Topological domain	771 – 783	13	Cytoplasmic Potential
	Transmembrane	784 – 806	23	Helical; Name=6; Potential
	Topological domain	807 – 819	13	Extracellular Potential
	Transmembrane	820 – 845	26	Helical; Name=7; Potential
	Topological domain	846 – 877	32	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	451	1	N-linked (GlcNAc...) Potential
	Glycosylation	479	1	N-linked (GlcNAc...) Potential
	Glycosylation	567	1	N-linked (GlcNAc...) Potential
	Disulfide bond	57 ↔ 99		By similarity
	Disulfide bond	244 ↔ 536		By similarity
	Disulfide bond	367 ↔ 383		By similarity
	Disulfide bond	423 ↔ 430		By similarity
	Disulfide bond	518 ↔ 537		By similarity
	Disulfide bond	522 ↔ 540		By similarity
	Disulfide bond	543 ↔ 555		By similarity
	Disulfide bond	558 ↔ 571		By similarity
Natural variations
	Natural variant	59	1	Q → P. Ref.1 Corresponds to variant rs2645329 [ dbSNP | Ensembl ].		VAR_059310
	Natural variant	150	1	G → S in CSNB1B. Ref.3		VAR_030756
	Natural variant	191	1	S → F in a breast cancer sample; somatic mutation. Ref.4		VAR_036195
	Natural variant	227	1	E → V. Corresponds to variant rs17078898 [ dbSNP | Ensembl ].		VAR_055876
	Natural variant	236	1	I → F. Corresponds to variant rs17078896 [ dbSNP | Ensembl ].		VAR_055877
	Natural variant	712	1	M → V. Corresponds to variant rs17078877 [ dbSNP | Ensembl ].		VAR_055878
	Natural variant	781	1	E → K in CSNB1B. Ref.3		VAR_030757
	Natural variant	807	1	A → V. Corresponds to variant rs17078874 [ dbSNP | Ensembl ].		VAR_055879
	Natural variant	817	1	T → S. Corresponds to variant rs17078857 [ dbSNP | Ensembl ].		VAR_055880

Sequences

	Sequence		Length	Mass (Da)
	O15303 [UniParc]. Last modified June 16, 2009. Version 2. Checksum: 2AB27C5627B388C6	FASTA	877	95,468
	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

References

	« Hide 'large scale' referencesShow '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: 9215706] [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. , 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: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15781871] [Abstract] Cited for: VARIANTS CSNB1B SER-150 AND LYS-781.
[4]	"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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-191.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U82083 Genomic DNA. Translation: AAB82068.1. AC104117 Genomic DNA. No translation available.
IPI	IPI00006089.
RefSeq	NP_000834.2. NM_000843.3.
UniGene	Hs.248131.
3D structure databases
ProteinModelPortal	O15303.
SMR	O15303. Positions 31-576.
ModBase	Search...
Protein-protein interaction databases
STRING	O15303.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	O15303.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000231188; ENSP00000231188; ENSG00000113262.
GeneID	2916.
KEGG	hsa:2916.
UCSC	uc003mjr.1. human.
Organism-specific databases
CTD	2916.
GeneCards	GC05M178392.
HGNC	HGNC:4598. GRM6.
MIM	257270. phenotype. 604096. gene.
neXtProt	NX_O15303.
Orphanet	215. Congenital stationary night blindness.
PharmGKB	PA28995.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG107965.
OMA	KKEQGVH.
OrthoDB	EOG4H4634.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	O15303.
Bgee	O15303.
CleanEx	HS_GRM6.
Genevestigator	O15303.
GermOnline	ENSG00000113262. Homo sapiens.
Family and domain databases
InterPro	IPR001828. 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. [Graphical view]
KO	K04608.
Pfam	PF00003. 7tm_3. 1 hit. PF01094. ANF_receptor. 1 hit. PF07562. NCD3G. 1 hit. [Graphical view]
PRINTS	PR00248. GPCRMGR. PR01056. MTABOTROPC6R. PR00593. MTABOTROPICR.
PROSITE	PS00979. 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]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

GRM6_HUMAN

Accession

Primary (citable) accession number: O15303

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	June 16, 2009
Last modified:	January 25, 2012
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.