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Protein

Metabotropic glutamate receptor 8

Gene

GRM8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei156GlutamateBy similarity1
Binding sitei227GlutamateBy similarity1
Binding sitei309GlutamateBy similarity1
Binding sitei401GlutamateBy similarity1

GO - Molecular functioni

  • glutamate receptor activity Source: UniProtKB
  • G-protein coupled receptor activity Source: UniProtKB

GO - Biological processi

  • adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: UniProtKB
  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: Reactome
  • regulation of synaptic transmission, glutamatergic Source: GO_Central
  • visual perception Source: ProtInc

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processSensory transduction

Enzyme and pathway databases

ReactomeiR-HSA-418594 G alpha (i) signalling events
R-HSA-420499 Class C/3 (Metabotropic glutamate/pheromone receptors)

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 8
Short name:
mGluR8
Gene namesi
Name:GRM8
Synonyms:GPRC1H, MGLUR8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000179603.17
HGNCiHGNC:4600 GRM8
MIMi601116 gene
neXtProtiNX_O00222

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini34 – 583ExtracellularSequence analysisAdd BLAST550
Transmembranei584 – 608Helical; Name=1Sequence analysisAdd BLAST25
Topological domaini609 – 620CytoplasmicSequence analysisAdd BLAST12
Transmembranei621 – 641Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini642 – 647ExtracellularSequence analysis6
Transmembranei648 – 668Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini669 – 695CytoplasmicSequence analysisAdd BLAST27
Transmembranei696 – 716Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini717 – 746ExtracellularSequence analysisAdd BLAST30
Transmembranei747 – 768Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini769 – 781CytoplasmicSequence analysisAdd BLAST13
Transmembranei782 – 803Helical; Name=6Sequence analysisAdd BLAST22
Topological domaini804 – 818ExtracellularSequence analysisAdd BLAST15
Transmembranei819 – 843Helical; Name=7Sequence analysisAdd BLAST25
Topological domaini844 – 908CytoplasmicSequence analysisAdd BLAST65

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2918
OpenTargetsiENSG00000179603
PharmGKBiPA28997

Chemistry databases

ChEMBLiCHEMBL3228
DrugBankiDB00142 L-Glutamic Acid
GuidetoPHARMACOLOGYi296

Polymorphism and mutation databases

BioMutaiGRM8

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000001294134 – 908Metabotropic glutamate receptor 8Add BLAST875

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi64 ↔ 106By similarity
Glycosylationi95N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi246 ↔ 534By similarity
Glycosylationi298N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi369 ↔ 384By similarity
Disulfide bondi424 ↔ 431By similarity
Glycosylationi452N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi480N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi516 ↔ 535By similarity
Disulfide bondi520 ↔ 538By similarity
Disulfide bondi541 ↔ 553By similarity
Disulfide bondi556 ↔ 569By similarity
Glycosylationi565N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki882Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiO00222
PeptideAtlasiO00222
PRIDEiO00222

PTM databases

iPTMnetiO00222
PhosphoSitePlusiO00222

Expressioni

Gene expression databases

BgeeiENSG00000179603
CleanExiHS_GRM8
ExpressionAtlasiO00222 baseline and differential
GenevisibleiO00222 HS

Organism-specific databases

HPAiHPA051481

Interactioni

Subunit structurei

Interacts with PICK1.By similarity

Protein-protein interaction databases

CORUMiO00222
STRINGi9606.ENSP00000344173

Chemistry databases

BindingDBiO00222

Structurei

Secondary structure

1908
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 42Combined sources4
Beta strandi45 – 52Combined sources8
Beta strandi55 – 57Combined sources3
Beta strandi63 – 67Combined sources5
Turni69 – 72Combined sources4
Helixi73 – 88Combined sources16
Turni92 – 95Combined sources4
Beta strandi98 – 104Combined sources7
Helixi109 – 116Combined sources8
Helixi117 – 119Combined sources3
Beta strandi147 – 151Combined sources5
Helixi156 – 166Combined sources11
Turni167 – 170Combined sources4
Beta strandi173 – 177Combined sources5
Helixi181 – 184Combined sources4
Turni186 – 188Combined sources3
Beta strandi192 – 196Combined sources5
Helixi199 – 213Combined sources15
Beta strandi217 – 225Combined sources9
Helixi226 – 241Combined sources16
Beta strandi242 – 244Combined sources3
Beta strandi246 – 253Combined sources8
Helixi261 – 269Combined sources9
Beta strandi277 – 281Combined sources5
Helixi284 – 296Combined sources13
Turni300 – 302Combined sources3
Beta strandi304 – 307Combined sources4
Turni309 – 313Combined sources5
Turni316 – 320Combined sources5
Turni322 – 327Combined sources6
Beta strandi329 – 334Combined sources6
Helixi339 – 346Combined sources8
Turni350 – 352Combined sources3
Helixi359 – 367Combined sources9
Turni390 – 392Combined sources3
Helixi402 – 423Combined sources22
Beta strandi424 – 426Combined sources3
Helixi432 – 434Combined sources3
Helixi439 – 448Combined sources10
Beta strandi450 – 452Combined sources3
Beta strandi458 – 460Combined sources3
Beta strandi463 – 465Combined sources3
Beta strandi470 – 478Combined sources9
Beta strandi483 – 497Combined sources15
Helixi499 – 501Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6BSZX-ray2.65A/B37-514[»]
6BT5X-ray2.92A/B37-514[»]
ProteinModelPortaliO00222
SMRiO00222
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni177 – 179Glutamate bindingBy similarity3

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1056 Eukaryota
ENOG410XR6W LUCA
GeneTreeiENSGT00760000118884
HOVERGENiHBG107965
InParanoidiO00222
KOiK04608
OMAiVDFPMVK
OrthoDBiEOG091G177R
PhylomeDBiO00222
TreeFamiTF313240

Family and domain databases

Gene3Di2.10.50.30, 1 hit
InterProiView protein in InterPro
IPR001828 ANF_lig-bd_rcpt
IPR000337 GPCR_3
IPR011500 GPCR_3_9-Cys_dom
IPR038550 GPCR_3_9-Cys_sf
IPR017978 GPCR_3_C
IPR017979 GPCR_3_CS
IPR000162 GPCR_3_mtglu_rcpt
IPR000144 GPCR_3_mtglu_rcpt_8
IPR028082 Peripla_BP_I
PfamiView protein in Pfam
PF00003 7tm_3, 1 hit
PF01094 ANF_receptor, 1 hit
PF07562 NCD3G, 1 hit
PRINTSiPR00248 GPCRMGR
PR01058 MTABOTROPC8R
PR00593 MTABOTROPICR
SUPFAMiSSF53822 SSF53822, 1 hit
PROSITEiView protein in 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

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: O00222-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MVCEGKRSAS CPCFFLLTAK FYWILTMMQR THSQEYAHSI RVDGDIILGG
60 70 80 90 100
LFPVHAKGER GVPCGELKKE KGIHRLEAML YAIDQINKDP DLLSNITLGV
110 120 130 140 150
RILDTCSRDT YALEQSLTFV QALIEKDASD VKCANGDPPI FTKPDKISGV
160 170 180 190 200
IGAAASSVSI MVANILRLFK IPQISYASTA PELSDNTRYD FFSRVVPPDS
210 220 230 240 250
YQAQAMVDIV TALGWNYVST LASEGNYGES GVEAFTQISR EIGGVCIAQS
260 270 280 290 300
QKIPREPRPG EFEKIIKRLL ETPNARAVIM FANEDDIRRI LEAAKKLNQS
310 320 330 340 350
GHFLWIGSDS WGSKIAPVYQ QEEIAEGAVT ILPKRASIDG FDRYFRSRTL
360 370 380 390 400
ANNRRNVWFA EFWEENFGCK LGSHGKRNSH IKKCTGLERI ARDSSYEQEG
410 420 430 440 450
KVQFVIDAVY SMAYALHNMH KDLCPGYIGL CPRMSTIDGK ELLGYIRAVN
460 470 480 490 500
FNGSAGTPVT FNENGDAPGR YDIFQYQITN KSTEYKVIGH WTNQLHLKVE
510 520 530 540 550
DMQWAHREHT HPASVCSLPC KPGERKKTVK GVPCCWHCER CEGYNYQVDE
560 570 580 590 600
LSCELCPLDQ RPNMNRTGCQ LIPIIKLEWH SPWAVVPVFV AILGIIATTF
610 620 630 640 650
VIVTFVRYND TPIVRASGRE LSYVLLTGIF LCYSITFLMI AAPDTIICSF
660 670 680 690 700
RRVFLGLGMC FSYAALLTKT NRIHRIFEQG KKSVTAPKFI SPASQLVITF
710 720 730 740 750
SLISVQLLGV FVWFVVDPPH IIIDYGEQRT LDPEKARGVL KCDISDLSLI
760 770 780 790 800
CSLGYSILLM VTCTVYAIKT RGVPETFNEA KPIGFTMYTT CIIWLAFIPI
810 820 830 840 850
FFGTAQSAEK MYIQTTTLTV SMSLSASVSL GMLYMPKVYI IIFHPEQNVQ
860 870 880 890 900
KRKRSFKAVV TAATMQSKLI QKGNDRPNGE VKSELCESLE TNTSSTKTTY

ISYSNHSI
Length:908
Mass (Da):101,741
Last modified:December 1, 2000 - v2
Checksum:i95C2D5883DAF6FDE
GO
Isoform B (identifier: O00222-2) [UniParc]FASTAAdd to basket
Also known as: mGluR8b

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

Show »
Length:908
Mass (Da):101,608
Checksum:i9F0D1EDB226C16D6
GO
Isoform C (identifier: O00222-3) [UniParc]FASTAAdd to basket
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.

Show »
Length:501
Mass (Da):55,948
Checksum:iCF684628F8123919
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti194R → A in AAB72040 (PubMed:9299241).Curated1
Sequence conflicti460T → I in AAB72040 (PubMed:9299241).Curated1
Sequence conflicti591A → V in ABY87924 (Ref. 5) Curated1
Sequence conflicti642A → G in AAB72040 (PubMed:9299241).Curated1
Sequence conflicti904S → T in AAB72040 (PubMed:9299241).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01444610S → C1 PublicationCorresponds to variant dbSNP:rs769194Ensembl.1
Natural variantiVAR_01444721F → C. Corresponds to variant dbSNP:rs769202Ensembl.1
Natural variantiVAR_049278265I → T1 PublicationCorresponds to variant dbSNP:rs17150343Ensembl.1
Natural variantiVAR_054752343R → Q1 PublicationCorresponds to variant dbSNP:rs13309334Ensembl.1
Natural variantiVAR_054477362F → Y1 PublicationCorresponds to variant dbSNP:rs78124913Ensembl.1
Natural variantiVAR_054478368G → D1 PublicationCorresponds to variant dbSNP:rs78947184Ensembl.1
Natural variantiVAR_014448392R → Q. Corresponds to variant dbSNP:rs2234947Ensembl.1
Natural variantiVAR_054479430L → F1 PublicationCorresponds to variant dbSNP:rs75863532Ensembl.1
Natural variantiVAR_014449548V → G. Corresponds to variant dbSNP:rs2234948Ensembl.1
Natural variantiVAR_054753768I → N1 PublicationCorresponds to variant dbSNP:rs1051433Ensembl.1
Natural variantiVAR_054754902S → I. Corresponds to variant dbSNP:rs10225567Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002033454 – 501SAGTP…LKVED → CRRGIQMSLPWPTLFTPSFS SSWAVLALLSLLMKTEMLLD VMISSSIK in isoform C. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_002034502 – 908Missing in isoform C. 1 PublicationAdd BLAST407
Alternative sequenceiVSP_002032893 – 908TSSTK…SNHSI → SKSSVEFPMVKSGSTS in isoform B. 2 PublicationsAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS47696.1 [O00222-2]
CCDS5794.1 [O00222-1]
RefSeqiNP_000836.2, NM_000845.2 [O00222-1]
NP_001120795.1, NM_001127323.1 [O00222-2]
XP_006716001.1, XM_006715938.3 [O00222-1]
XP_011514393.1, XM_011516091.1 [O00222-1]
XP_011514394.1, XM_011516092.2 [O00222-2]
XP_016867563.1, XM_017012074.1 [O00222-1]
UniGeneiHs.449625

Genome annotation databases

EnsembliENST00000339582; ENSP00000344173; ENSG00000179603 [O00222-1]
ENST00000341617; ENSP00000345747; ENSG00000179603 [O00222-3]
ENST00000358373; ENSP00000351142; ENSG00000179603 [O00222-2]
ENST00000472701; ENSP00000419832; ENSG00000179603 [O00222-2]
GeneIDi2918
KEGGihsa:2918
UCSCiuc003vlr.3 human [O00222-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGRM8_HUMAN
AccessioniPrimary (citable) accession number: O00222
Secondary accession number(s): A4D0Y3
, B0FZ74, B0M0L0, O15493, O95945, O95946, Q3MIV9, Q52M02, Q6J165
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 1, 2000
Last modified: April 25, 2018
This is version 167 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health