GRM8

Protein identityUniProt · HPA

UniProt accession

O00222

Gene

GRM8

Ensembl

ENSG00000179603

Chromosome

7

Canonical length

908 aa

Protein class

G-protein coupled receptors, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

908 residues, UniProt reviewed canonical sequence.

>O00222|GRM8
     1  MVCEGKRSAS CPCFFLLTAK FYWILTMMQR THSQEYAHSI RVDGDIILGG LFPVHAKGER
    61  GVPCGELKKE KGIHRLEAML YAIDQINKDP DLLSNITLGV RILDTCSRDT YALEQSLTFV
   121  QALIEKDASD VKCANGDPPI FTKPDKISGV IGAAASSVSI MVANILRLFK IPQISYASTA
   181  PELSDNTRYD FFSRVVPPDS YQAQAMVDIV TALGWNYVST LASEGNYGES GVEAFTQISR
   241  EIGGVCIAQS QKIPREPRPG EFEKIIKRLL ETPNARAVIM FANEDDIRRI LEAAKKLNQS
   301  GHFLWIGSDS WGSKIAPVYQ QEEIAEGAVT ILPKRASIDG FDRYFRSRTL ANNRRNVWFA
   361  EFWEENFGCK LGSHGKRNSH IKKCTGLERI ARDSSYEQEG KVQFVIDAVY SMAYALHNMH
   421  KDLCPGYIGL CPRMSTIDGK ELLGYIRAVN FNGSAGTPVT FNENGDAPGR YDIFQYQITN
   481  KSTEYKVIGH WTNQLHLKVE DMQWAHREHT HPASVCSLPC KPGERKKTVK GVPCCWHCER
   541  CEGYNYQVDE LSCELCPLDQ RPNMNRTGCQ LIPIIKLEWH SPWAVVPVFV AILGIIATTF
   601  VIVTFVRYND TPIVRASGRE LSYVLLTGIF LCYSITFLMI AAPDTIICSF RRVFLGLGMC
   661  FSYAALLTKT NRIHRIFEQG KKSVTAPKFI SPASQLVITF SLISVQLLGV FVWFVVDPPH
   721  IIIDYGEQRT LDPEKARGVL KCDISDLSLI CSLGYSILLM VTCTVYAIKT RGVPETFNEA
   781  KPIGFTMYTT CIIWLAFIPI FFGTAQSAEK MYIQTTTLTV SMSLSASVSL GMLYMPKVYI
   841  IIFHPEQNVQ KRKRSFKAVV TAATMQSKLI QKGNDRPNGE VKSELCESLE TNTSSTKTTY
   901  ISYSNHSI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRM8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

20 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.64

gnomAD pLI

0

gnomAD missense Z

0.91

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway
• adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• G protein-coupled glutamate receptor signaling pathway
• regulation of synaptic transmission, glutamatergic
• visual perception

Molecular functions

• G protein-coupled receptor activity
• glutamate receptor activity
• group III metabotropic glutamate receptor activity

Cellular components

• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• GPCR, family 3, metabotropic glutamate receptor
• GPCR, family 3
• Receptor, ligand binding region
• GPCR, family 3, nine cysteines domain
• GPCR family 3, C-terminal
• GPCR, family 3, conserved site
• Periplasmic binding protein-like I
• GPCR, family 3, nine cysteines domain superfamily
• Metabotropic Glutamate Receptor
• 7 transmembrane sweet-taste receptor of 3 GCPR
• Receptor family ligand binding region
• Nine Cysteines Domain of family 3 GPCR
• GPCR, family 3, metabotropic glutamate receptor 8

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Isopeptide bond
• Membrane
• Receptor
• Sensory transduction
• Signal
• Transducer
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of GRM8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PICK1