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Protein

Metabotropic glutamate receptor 8

Gene

GRM8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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
  • group III metabotropic glutamate receptor activity Source: GO_Central

GO - Biological processi

  • adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: UniProtKB
  • negative regulation of cAMP biosynthetic process Source: UniProtKB
  • regulation of synaptic transmission, glutamatergic Source: GO_Central
  • sensory perception of smell Source: UniProtKB-KW
  • visual perception Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Olfaction, Sensory 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

HGNCiHGNC:4600. GRM8.

Subcellular locationi

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

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • presynaptic membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2918.
OpenTargetsiENSG00000179603.
PharmGKBiPA28997.

Chemistry databases

ChEMBLiCHEMBL3228.
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...)Sequence analysis1
Disulfide bondi246 ↔ 534By similarity
Glycosylationi298N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi369 ↔ 384By similarity
Disulfide bondi424 ↔ 431By similarity
Glycosylationi452N-linked (GlcNAc...)Sequence analysis1
Glycosylationi480N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi516 ↔ 535By similarity
Disulfide bondi520 ↔ 538By similarity
Disulfide bondi541 ↔ 553By similarity
Disulfide bondi556 ↔ 569By similarity
Glycosylationi565N-linked (GlcNAc...)Sequence 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

STRINGi9606.ENSP00000344173.

Chemistry databases

BindingDBiO00222.

Structurei

3D structure databases

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.
OMAiRTHGQEY.
OrthoDBiEOG091G177R.
PhylomeDBiO00222.
TreeFamiTF313240.

Family and domain databases

InterProiIPR001828. 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]
PANTHERiPTHR24060:SF26. PTHR24060:SF26. 1 hit.
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01058. MTABOTROPC8R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]

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 → C.1 PublicationCorresponds to variant rs769194dbSNPEnsembl.1
Natural variantiVAR_01444721F → C.Corresponds to variant rs769202dbSNPEnsembl.1
Natural variantiVAR_049278265I → T.1 PublicationCorresponds to variant rs17150343dbSNPEnsembl.1
Natural variantiVAR_054752343R → Q.1 PublicationCorresponds to variant rs13309334dbSNPEnsembl.1
Natural variantiVAR_054477362F → Y.1 PublicationCorresponds to variant rs78124913dbSNPEnsembl.1
Natural variantiVAR_054478368G → D.1 PublicationCorresponds to variant rs78947184dbSNPEnsembl.1
Natural variantiVAR_014448392R → Q.Corresponds to variant rs2234947dbSNPEnsembl.1
Natural variantiVAR_054479430L → F.1 PublicationCorresponds to variant rs75863532dbSNPEnsembl.1
Natural variantiVAR_014449548V → G.Corresponds to variant rs2234948dbSNPEnsembl.1
Natural variantiVAR_054753768I → N.1 PublicationCorresponds to variant rs1051433dbSNPEnsembl.1
Natural variantiVAR_054754902S → I.Corresponds to variant rs10225567dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

NIEHS-SNPs

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.

3D structure databases

ProteinModelPortaliO00222.
SMRiO00222.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000344173.

Chemistry databases

BindingDBiO00222.
ChEMBLiCHEMBL3228.
GuidetoPHARMACOLOGYi296.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO00222.
PhosphoSitePlusiO00222.

Polymorphism and mutation databases

BioMutaiGRM8.

Proteomic databases

PaxDbiO00222.
PeptideAtlasiO00222.
PRIDEiO00222.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi2918.
DisGeNETi2918.
GeneCardsiGRM8.
H-InvDBHIX0025292.
HGNCiHGNC:4600. GRM8.
HPAiHPA051481.
MIMi601116. gene.
neXtProtiNX_O00222.
OpenTargetsiENSG00000179603.
PharmGKBiPA28997.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1056. Eukaryota.
ENOG410XR6W. LUCA.
GeneTreeiENSGT00760000118884.
HOVERGENiHBG107965.
InParanoidiO00222.
KOiK04608.
OMAiRTHGQEY.
OrthoDBiEOG091G177R.
PhylomeDBiO00222.
TreeFamiTF313240.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiGRM8. human.
GeneWikiiMetabotropic_glutamate_receptor_8.
GenomeRNAii2918.
PROiO00222.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000179603.
CleanExiHS_GRM8.
ExpressionAtlasiO00222. baseline and differential.
GenevisibleiO00222. HS.

Family and domain databases

InterProiIPR001828. 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]
PANTHERiPTHR24060:SF26. PTHR24060:SF26. 1 hit.
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01058. MTABOTROPC8R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiGRM8_HUMAN
AccessioniPrimary (citable) accession number: O00222
Secondary accession number(s): A4D0Y3
, B0FZ74, B0M0L0, O15493, O95945, O95946, Q3MIV9, Q52M02, Q6J165
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 1, 2000
Last modified: November 2, 2016
This is version 155 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.