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O00222 (GRM8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metabotropic glutamate receptor 8

Short name=mGluR8
Gene names
Name:GRM8
Synonyms:GPRC1H, MGLUR8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length908 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

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. Ref.2

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 processOlfaction
Sensory transduction
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Isopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway

Inferred from mutant phenotype Ref.2. Source: UniProtKB

negative regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 11166323. Source: UniProtKB

regulation of synaptic transmission, glutamatergic

Inferred from Biological aspect of Ancestor. Source: RefGenome

sensory perception of smell

Inferred from electronic annotation. Source: UniProtKB-KW

visual perception

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentintegral component of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Traceable author statement. Source: Reactome

presynaptic membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionG-protein coupled receptor activity

Inferred from mutant phenotype Ref.2. Source: UniProtKB

glutamate receptor activity

Inferred from mutant phenotype Ref.2. Source: UniProtKB

group III metabotropic glutamate receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Potential
Chain34 – 908875Metabotropic glutamate receptor 8
PRO_0000012941

Regions

Topological domain34 – 583550Extracellular Potential
Transmembrane584 – 60825Helical; Name=1; Potential
Topological domain609 – 62012Cytoplasmic Potential
Transmembrane621 – 64121Helical; Name=2; Potential
Topological domain642 – 6476Extracellular Potential
Transmembrane648 – 66821Helical; Name=3; Potential
Topological domain669 – 69527Cytoplasmic Potential
Transmembrane696 – 71621Helical; Name=4; Potential
Topological domain717 – 74630Extracellular Potential
Transmembrane747 – 76822Helical; Name=5; Potential
Topological domain769 – 78113Cytoplasmic Potential
Transmembrane782 – 80322Helical; Name=6; Potential
Topological domain804 – 81815Extracellular Potential
Transmembrane819 – 84325Helical; Name=7; Potential
Topological domain844 – 90865Cytoplasmic Potential
Region177 – 1793Glutamate binding By similarity

Sites

Binding site1561Glutamate By similarity
Binding site2271Glutamate By similarity
Binding site3091Glutamate By similarity
Binding site4011Glutamate By similarity

Amino acid modifications

Glycosylation951N-linked (GlcNAc...) Potential
Glycosylation2981N-linked (GlcNAc...) Potential
Glycosylation4521N-linked (GlcNAc...) Potential
Glycosylation4801N-linked (GlcNAc...) Potential
Glycosylation5651N-linked (GlcNAc...) Potential
Disulfide bond64 ↔ 106 By similarity
Disulfide bond246 ↔ 534 By similarity
Disulfide bond369 ↔ 384 By similarity
Disulfide bond424 ↔ 431 By similarity
Disulfide bond516 ↔ 535 By similarity
Disulfide bond520 ↔ 538 By similarity
Disulfide bond541 ↔ 553 By similarity
Disulfide bond556 ↔ 569 By similarity
Cross-link882Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO-1) By similarity

Natural variations

Alternative sequence454 – 50148SAGTP…LKVED → CRRGIQMSLPWPTLFTPSFS SSWAVLALLSLLMKTEMLLD VMISSSIK in isoform C.
VSP_002033
Alternative sequence502 – 908407Missing in isoform C.
VSP_002034
Alternative sequence893 – 90816TSSTK…SNHSI → SKSSVEFPMVKSGSTS in isoform B.
VSP_002032
Natural variant101S → C. Ref.6
Corresponds to variant rs769194 [ dbSNP | Ensembl ].
VAR_014446
Natural variant211F → C.
Corresponds to variant rs769202 [ dbSNP | Ensembl ].
VAR_014447
Natural variant2651I → T. Ref.6
Corresponds to variant rs17150343 [ dbSNP | Ensembl ].
VAR_049278
Natural variant3431R → Q. Ref.7
Corresponds to variant rs13309334 [ dbSNP | Ensembl ].
VAR_054752
Natural variant3621F → Y. Ref.6
VAR_054477
Natural variant3681G → D. Ref.6
VAR_054478
Natural variant3921R → Q.
Corresponds to variant rs2234947 [ dbSNP | Ensembl ].
VAR_014448
Natural variant4301L → F. Ref.6
VAR_054479
Natural variant5481V → G.
Corresponds to variant rs2234948 [ dbSNP | Ensembl ].
VAR_014449
Natural variant7681I → N. Ref.2
Corresponds to variant rs1051433 [ dbSNP | Ensembl ].
VAR_054753
Natural variant9021S → I.
Corresponds to variant rs10225567 [ dbSNP | Ensembl ].
VAR_054754

Experimental info

Sequence conflict1941R → A in AAB72040. Ref.1
Sequence conflict4601T → I in AAB72040. Ref.1
Sequence conflict5911A → V in ABY87924. Ref.5
Sequence conflict6421A → G in AAB72040. Ref.1
Sequence conflict9041S → T in AAB72040. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform A (mGluR8a) [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 95C2D5883DAF6FDE

FASTA908101,741
        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 

« Hide

Isoform B (mGluR8b) [UniParc].

Checksum: 9F0D1EDB226C16D6
Show »

FASTA908101,608
Isoform C (mGluR8c) [UniParc].

Checksum: CF684628F8123919
Show »

FASTA50155,948

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
Tissue: Colon.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS47696.1. [O00222-2]
CCDS5794.1. [O00222-1]
RefSeqNP_000836.2. NM_000845.2. [O00222-1]
NP_001120795.1. NM_001127323.1. [O00222-2]
XP_006716001.1. XM_006715938.1. [O00222-1]
UniGeneHs.449625.

3D structure databases

ProteinModelPortalO00222.
SMRO00222. Positions 38-849.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBO00222.
ChEMBLCHEMBL3228.
DrugBankDB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGY296.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteO00222.

Proteomic databases

PaxDbO00222.
PRIDEO00222.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000339582; ENSP00000344173; ENSG00000179603. [O00222-1]
ENST00000341617; ENSP00000345747; ENSG00000179603. [O00222-3]
ENST00000358373; ENSP00000351142; ENSG00000179603. [O00222-2]
ENST00000405249; ENSP00000385731; ENSG00000179603. [O00222-3]
ENST00000444921; ENSP00000409790; ENSG00000179603. [O00222-1]
ENST00000472701; ENSP00000419832; ENSG00000179603. [O00222-2]
GeneID2918.
KEGGhsa:2918.
UCSCuc003vlr.2. human. [O00222-1]
uc003vlt.2. human. [O00222-2]

Organism-specific databases

CTD2918.
GeneCardsGC07M126078.
H-InvDBHIX0025292.
HGNCHGNC:4600. GRM8.
HPAHPA051481.
MIM601116. gene.
neXtProtNX_O00222.
PharmGKBPA28997.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295200.
HOVERGENHBG107965.
InParanoidO00222.
KOK04608.
OMARTHGQEY.
OrthoDBEOG7Z0JXG.
PhylomeDBO00222.
TreeFamTF313240.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressO00222.
BgeeO00222.
CleanExHS_GRM8.
GenevestigatorO00222.

Family and domain databases

InterProIPR001828. 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.
IPR000144. GPCR_3_mtglu_rcpt_8.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSPR00248. GPCRMGR.
PR01058. MTABOTROPC8R.
PR00593. MTABOTROPICR.
SUPFAMSSF53822. SSF53822. 1 hit.
PROSITEPS00979. 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]
ProtoNetSearch...

Other

GeneWikiMetabotropic_glutamate_receptor_8.
GenomeRNAi2918.
NextBio11569.
PROO00222.
SOURCESearch...

Entry information

Entry nameGRM8_HUMAN
AccessionPrimary (citable) accession number: O00222
Secondary accession number(s): A4D0Y3 expand/collapse secondary AC list , 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: July 9, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries