Reviewed, UniProtKB/Swiss-Prot O00222 (GRM8_HUMAN)

Names and origin

Protein names

Recommended name:
    Metabotropic glutamate receptor 8
      Short name=mGluR8

Gene names

Name:	GRM8
Synonyms:	GPRC1H, MGLUR8

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	908 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Receptor for glutamate. The activity of this receptor is mediated by a G-protein that inhibits adenylate cyclase activity.
Subunit structure	Interacts with PICK1 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 3 family.

Ontologies

Keywords
Biological process	Olfaction Sensory transduction
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Isopeptide bond Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of adenylate cyclase activity Ref.2 Traceable author statement. Source: ProtInc negative regulation of cAMP biosynthetic process Inferred from direct assay. Source: UniProtKB response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of smell Inferred from electronic annotation. Source: UniProtKB-KW visual perception Ref.2 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc
Molecular function	G-protein coupled receptor activity Ref.2 Traceable author statement. Source: UniProtKB glutamate receptor activity Ref.2 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: O00222-1)

Also known as: mGluR8a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: O00222-2)

Also known as: mGluR8b;

The sequence of this isoform differs from the canonical sequence as follows:
     893-908: TSSTKTTYISYSNHSI → SKSSVEFPMVKSGSTS

Isoform C (identifier: O00222-3)

Also known as: mGluR8c;

The sequence of this isoform differs from the canonical sequence as follows:
     454-501: SAGTPVTFNE...TNQLHLKVED → CRRGIQMSLP...LDVMISSSIK
     502-908: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 33	33	Potential
	Chain	34 – 908	875	Metabotropic glutamate receptor 8		PRO_0000012941
Regions
	Topological domain	34 – 583	550	Extracellular Potential
	Transmembrane	584 – 608	25	1 Potential
	Topological domain	609 – 620	12	Cytoplasmic Potential
	Transmembrane	621 – 641	21	2 Potential
	Topological domain	642 – 647	6	Extracellular Potential
	Transmembrane	648 – 668	21	3 Potential
	Topological domain	669 – 695	27	Cytoplasmic Potential
	Transmembrane	696 – 716	21	4 Potential
	Topological domain	717 – 746	30	Extracellular Potential
	Transmembrane	747 – 768	22	5 Potential
	Topological domain	769 – 781	13	Cytoplasmic Potential
	Transmembrane	782 – 803	22	6 Potential
	Topological domain	804 – 818	15	Extracellular Potential
	Transmembrane	819 – 843	25	7 Potential
	Topological domain	844 – 908	65	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	95	1	N-linked (GlcNAc...) Potential
	Glycosylation	298	1	N-linked (GlcNAc...) Potential
	Glycosylation	452	1	N-linked (GlcNAc...) Potential
	Glycosylation	480	1	N-linked (GlcNAc...) Potential
	Glycosylation	565	1	N-linked (GlcNAc...) Potential
	Cross-link	882		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) By similarity
Natural variations
	Alternative sequence	454 – 501	48	SAGTP…LKVED → CRRGIQMSLPWPTLFTPSFS SSWAVLALLSLLMKTEMLLD VMISSSIK in isoform C.		VSP_002033
	Alternative sequence	502 – 908	407	Missing in isoform C.		VSP_002034
	Alternative sequence	893 – 908	16	TSSTK…SNHSI → SKSSVEFPMVKSGSTS in isoform B.		VSP_002032
	Natural variant	10	1	S → C: dbSNP rs769194. Ref.6		VAR_014446
	Natural variant	21	1	F → C: dbSNP rs769202.		VAR_014447
	Natural variant	265	1	I → T: dbSNP rs17150343. Ref.6		VAR_049278
	Natural variant	343	1	R → Q: dbSNP rs13309334. Ref.7		VAR_054752
	Natural variant	362	1	F → Y		VAR_054477
	Natural variant	368	1	G → D		VAR_054478
	Natural variant	392	1	R → Q: dbSNP rs2234947.		VAR_014448
	Natural variant	430	1	L → F		VAR_054479
	Natural variant	548	1	V → G: dbSNP rs2234948.		VAR_014449
	Natural variant	768	1	I → N: dbSNP rs1051433. Ref.2		VAR_054753
	Natural variant	902	1	S → I: dbSNP rs10225567.		VAR_054754
Experimental info
	Sequence conflict	194	1	R → A in AAB72040. Ref.1
	Sequence conflict	460	1	T → I in AAB72040. Ref.1
	Sequence conflict	591	1	A → V in ABY87924. Ref.5
	Sequence conflict	642	1	A → G in AAB72040. Ref.1
	Sequence conflict	904	1	S → T in AAB72040. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (mGluR8a) [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 95C2D5883DAF6FDE	FASTA	908	101,741
	10 20 30 40 50 60 MVCEGKRSAS CPCFFLLTAK FYWILTMMQR THSQEYAHSI RVDGDIILGG LFPVHAKGER 70 80 90 100 110 120 GVPCGELKKE KGIHRLEAML YAIDQINKDP DLLSNITLGV RILDTCSRDT YALEQSLTFV 130 140 150 160 170 180 QALIEKDASD VKCANGDPPI FTKPDKISGV IGAAASSVSI MVANILRLFK IPQISYASTA 190 200 210 220 230 240 PELSDNTRYD FFSRVVPPDS YQAQAMVDIV TALGWNYVST LASEGNYGES GVEAFTQISR 250 260 270 280 290 300 EIGGVCIAQS QKIPREPRPG EFEKIIKRLL ETPNARAVIM FANEDDIRRI LEAAKKLNQS 310 320 330 340 350 360 GHFLWIGSDS WGSKIAPVYQ QEEIAEGAVT ILPKRASIDG FDRYFRSRTL ANNRRNVWFA 370 380 390 400 410 420 EFWEENFGCK LGSHGKRNSH IKKCTGLERI ARDSSYEQEG KVQFVIDAVY SMAYALHNMH 430 440 450 460 470 480 KDLCPGYIGL CPRMSTIDGK ELLGYIRAVN FNGSAGTPVT FNENGDAPGR YDIFQYQITN 490 500 510 520 530 540 KSTEYKVIGH WTNQLHLKVE DMQWAHREHT HPASVCSLPC KPGERKKTVK GVPCCWHCER 550 560 570 580 590 600 CEGYNYQVDE LSCELCPLDQ RPNMNRTGCQ LIPIIKLEWH SPWAVVPVFV AILGIIATTF 610 620 630 640 650 660 VIVTFVRYND TPIVRASGRE LSYVLLTGIF LCYSITFLMI AAPDTIICSF RRVFLGLGMC 670 680 690 700 710 720 FSYAALLTKT NRIHRIFEQG KKSVTAPKFI SPASQLVITF SLISVQLLGV FVWFVVDPPH 730 740 750 760 770 780 IIIDYGEQRT LDPEKARGVL KCDISDLSLI CSLGYSILLM VTCTVYAIKT RGVPETFNEA 790 800 810 820 830 840 KPIGFTMYTT CIIWLAFIPI FFGTAQSAEK MYIQTTTLTV SMSLSASVSL GMLYMPKVYI 850 860 870 880 890 900 IIFHPEQNVQ KRKRSFKAVV TAATMQSKLI QKGNDRPNGE VKSELCESLE TNTSSTKTTY ISYSNHSI
	Isoform B (mGluR8b). Checksum: 9F0D1EDB226C16D6	FASTA	908	101,608
	10 20 30 40 50 60 MVCEGKRSAS CPCFFLLTAK FYWILTMMQR THSQEYAHSI RVDGDIILGG LFPVHAKGER 70 80 90 100 110 120 GVPCGELKKE KGIHRLEAML YAIDQINKDP DLLSNITLGV RILDTCSRDT YALEQSLTFV 130 140 150 160 170 180 QALIEKDASD VKCANGDPPI FTKPDKISGV IGAAASSVSI MVANILRLFK IPQISYASTA 190 200 210 220 230 240 PELSDNTRYD FFSRVVPPDS YQAQAMVDIV TALGWNYVST LASEGNYGES GVEAFTQISR 250 260 270 280 290 300 EIGGVCIAQS QKIPREPRPG EFEKIIKRLL ETPNARAVIM FANEDDIRRI LEAAKKLNQS 310 320 330 340 350 360 GHFLWIGSDS WGSKIAPVYQ QEEIAEGAVT ILPKRASIDG FDRYFRSRTL ANNRRNVWFA 370 380 390 400 410 420 EFWEENFGCK LGSHGKRNSH IKKCTGLERI ARDSSYEQEG KVQFVIDAVY SMAYALHNMH 430 440 450 460 470 480 KDLCPGYIGL CPRMSTIDGK ELLGYIRAVN FNGSAGTPVT FNENGDAPGR YDIFQYQITN 490 500 510 520 530 540 KSTEYKVIGH WTNQLHLKVE DMQWAHREHT HPASVCSLPC KPGERKKTVK GVPCCWHCER 550 560 570 580 590 600 CEGYNYQVDE LSCELCPLDQ RPNMNRTGCQ LIPIIKLEWH SPWAVVPVFV AILGIIATTF 610 620 630 640 650 660 VIVTFVRYND TPIVRASGRE LSYVLLTGIF LCYSITFLMI AAPDTIICSF RRVFLGLGMC 670 680 690 700 710 720 FSYAALLTKT NRIHRIFEQG KKSVTAPKFI SPASQLVITF SLISVQLLGV FVWFVVDPPH 730 740 750 760 770 780 IIIDYGEQRT LDPEKARGVL KCDISDLSLI CSLGYSILLM VTCTVYAIKT RGVPETFNEA 790 800 810 820 830 840 KPIGFTMYTT CIIWLAFIPI FFGTAQSAEK MYIQTTTLTV SMSLSASVSL GMLYMPKVYI 850 860 870 880 890 900 IIFHPEQNVQ KRKRSFKAVV TAATMQSKLI QKGNDRPNGE VKSELCESLE TNSKSSVEFP MVKSGSTS
	Isoform C (mGluR8c). Checksum: CF684628F8123919	FASTA	501	55,948
	10 20 30 40 50 60 MVCEGKRSAS CPCFFLLTAK FYWILTMMQR THSQEYAHSI RVDGDIILGG LFPVHAKGER 70 80 90 100 110 120 GVPCGELKKE KGIHRLEAML YAIDQINKDP DLLSNITLGV RILDTCSRDT YALEQSLTFV 130 140 150 160 170 180 QALIEKDASD VKCANGDPPI FTKPDKISGV IGAAASSVSI MVANILRLFK IPQISYASTA 190 200 210 220 230 240 PELSDNTRYD FFSRVVPPDS YQAQAMVDIV TALGWNYVST LASEGNYGES GVEAFTQISR 250 260 270 280 290 300 EIGGVCIAQS QKIPREPRPG EFEKIIKRLL ETPNARAVIM FANEDDIRRI LEAAKKLNQS 310 320 330 340 350 360 GHFLWIGSDS WGSKIAPVYQ QEEIAEGAVT ILPKRASIDG FDRYFRSRTL ANNRRNVWFA 370 380 390 400 410 420 EFWEENFGCK LGSHGKRNSH IKKCTGLERI ARDSSYEQEG KVQFVIDAVY SMAYALHNMH 430 440 450 460 470 480 KDLCPGYIGL CPRMSTIDGK ELLGYIRAVN FNGCRRGIQM SLPWPTLFTP SFSSSWAVLA 490 500 LLSLLMKTEM LLDVMISSSI K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1." Scherer S.W., Soder S., Duvoisin R.M., Huizenga J.J., Tsui L.-C. Genomics 44:232-236(1997) [PubMed: 9299241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]	"Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells." Wu S., Wright R.A., Rockey P.K., Burgett S.G., Arnold J.S., Rosteck P.R. Jr., Johnson B.G., Schoepp D.D., Belagaje R.M. Brain Res. Mol. Brain Res. 53:88-97(1998) [PubMed: 9473604] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), VARIANT ASN-768.
[3]	"Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8." Malherbe P., Kratzeisen C., Lundstrom K., Richards J.G., Faull R.L.M., Mutel V. Brain Res. Mol. Brain Res. 67:201-210(1999) [PubMed: 10216218] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C). Tissue: Fetal brain.
[4]	"Homo sapiens metabotropic glutamate receptor." Stormann T.M., Simin R.T., Hammerland L.G., Fuller F.H. Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
[5]	Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). Tissue: Brain.
[6]	NIEHS SNPs program Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-10; THR-265; TYR-362; ASP-368 AND PHE-430.
[7]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM A), VARIANT GLN-343.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Tissue: Colon.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U95025 mRNA. Translation: AAB72040.1. U92459 mRNA. Translation: AAB51764.1. AJ236921 mRNA. Translation: CAB36968.1. AJ236922 mRNA. Translation: CAB36969.1. AY608335 mRNA. Translation: AAT37959.1. EU432125 mRNA. Translation: ABY87924.1. EU368948 Genomic DNA. Translation: ABY59657.1. CH236947 Genomic DNA. Translation: EAL24322.1. BC093725 mRNA. Translation: AAH93725.1. BC101675 mRNA. Translation: AAI01676.1.
IPI	IPI00219109. IPI00396012. IPI00413310.
RefSeq	NP_000836.2. NP_001120795.1.
UniGene	Hs.449625
3D structure databases
HSSP	HSSP built from PDB template 1EWT based on UniProtKB P23385.
SMR	O00222. Positions 38-504.
ModBase	Search...
Protein-protein interaction databases
STRING	O00222.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O00222.
Proteomic databases
PRIDE	O00222.
Genome annotation databases
Ensembl	ENST00000339582; ENSP00000344173; ENSG00000179603; Homo sapiens. [Genome view] ENST00000341617; ENSP00000345747; ENSG00000179603; Homo sapiens. [Genome view] ENST00000358373; ENSP00000351142; ENSG00000179603; Homo sapiens. [Genome view] ENST00000405249; ENSP00000385731; ENSG00000179603; Homo sapiens. [Genome view] ENST00000412160; ENSP00000398012; ENSG00000179603; Homo sapiens. [Genome view] ENST00000435661; ENSP00000387955; ENSG00000179603; Homo sapiens. [Genome view] ENST00000444921; ENSP00000409790; ENSG00000179603; Homo sapiens. [Genome view] ENST00000457830; ENSP00000415522; ENSG00000179603; Homo sapiens. [Genome view]
GeneID	2918.
KEGG	hsa:2918.
UCSC	uc003vlr.2. human. uc003vls.2. human. uc003vlt.2. human.
Organism-specific databases
CTD	2918.
GeneCards	GC07M125865.
H-InvDB	HIX0025292.
HGNC	HGNC:4600. GRM8.
MIM	601116. gene.
PharmGKB	PA28997.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O00222.
OMA	NQSGHFL.
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	O00222.
Bgee	O00222.
CleanEx	HS_GRM8.
Genevestigator	O00222.
GermOnline	ENSG00000179603. Homo sapiens.
Family and domain databases
InterPro	IPR001828. ANF_lig_bd_rcpt. IPR000337. GPCR_3. IPR017978. GPCR_3_C. IPR017979. GPCR_3_CS. IPR000162. GPCR_3_mtglu_rcpt. IPR000144. GPCR_3_mtglu_rcpt_8. IPR011500. GPCR_3_NCR. [Graphical view]
Pfam	PF00003. 7tm_3. 1 hit. PF01094. ANF_receptor. 1 hit. PF07562. NCD3G. 1 hit. [Graphical view]
PRINTS	PR00248. GPCRMGR. PR01058. MTABOTROPC8R. 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 Resources
DrugBank	DB00142. L-Glutamic Acid.
NextBio	11569.
SOURCE	Search...

Entry information

Entry name

GRM8_HUMAN

Accession

Primary (citable) accession number: O00222
Secondary accession number(s): A4D0Y3 , B0FZ74, B0M0L0, O15493, O95945, O95946, Q3MIV9, Q52M02, Q6J165

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	December 1, 2000
Last modified:	November 3, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.