GRM6

Protein identityUniProt · HPA

UniProt accession

O15303

Gene

GRM6

Ensembl

ENSG00000113262

Chromosome

5

Canonical length

877 aa

Protein class

Disease related genes, G-protein coupled receptors, Human disease related genes, Potential drug targets, Predicted membrane proteins

Quaternary structure

Homodimer

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. Mutations in this gene result in congenital stationary night blindness type 1B. [provided by RefSeq, May 2018]

Canonical amino-acid sequenceUniProt

877 residues, UniProt reviewed canonical sequence.

>O15303|GRM6
     1  MARPRRAREP LLVALLPLAW LAQAGLARAA GSVRLAGGLT LGGLFPVHAR GAAGRACGQL
    61  KKEQGVHRLE AMLYALDRVN ADPELLPGVR LGARLLDTCS RDTYALEQAL SFVQALIRGR
   121  GDGDEVGVRC PGGVPPLRPA PPERVVAVVG ASASSVSIMV ANVLRLFAIP QISYASTAPE
   181  LSDSTRYDFF SRVVPPDSYQ AQAMVDIVRA LGWNYVSTLA SEGNYGESGV EAFVQISREA
   241  GGVCIAQSIK IPREPKPGEF SKVIRRLMET PNARGIIIFA NEDDIRRVLE AARQANLTGH
   301  FLWVGSDSWG AKTSPILSLE DVAVGAITIL PKRASIDGFD QYFMTRSLEN NRRNIWFAEF
   361  WEENFNCKLT SSGTQSDDST RKCTGEERIG RDSTYEQEGK VQFVIDAVYA IAHALHSMHQ
   421  ALCPGHTGLC PAMEPTDGRM LLQYIRAVRF NGSAGTPVMF NENGDAPGRY DIFQYQATNG
   481  SASSGGYQAV GQWAETLRLD VEALQWSGDP HEVPSSLCSL PCGPGERKKM VKGVPCCWHC
   541  EACDGYRFQV DEFTCEACPG DMRPTPNHTG CRPTPVVRLS WSSPWAAPPL LLAVLGIVAT
   601  TTVVATFVRY NNTPIVRASG RELSYVLLTG IFLIYAITFL MVAEPGAAVC AARRLFLGLG
   661  TTLSYSALLT KTNRIYRIFE QGKRSVTPPP FISPTSQLVI TFSLTSLQVV GMIAWLGARP
   721  PHSVIDYEEQ RTVDPEQARG VLKCDMSDLS LIGCLGYSLL LMVTCTVYAI KARGVPETFN
   781  EAKPIGFTMY TTCIIWLAFV PIFFGTAQSA EKIYIQTTTL TVSLSLSASV SLGMLYVPKT
   841  YVILFHPEQN VQKRKRSLKA TSTVAAPPKG EDAEAHK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRM6 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)

0.29

Highest tissue expression

40 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GRM6.

Disease | AllUniProt

Conditions GRM6 is implicated in, by any mechanism.

• Night blindness, congenital stationary, 1B (CSNB1B) MIM:257270

Disease | GeneticClinVar

63 pathogenic / likely-pathogenic of 921 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital stationary night blindness 1B
• Retinal dystrophy
• Congenital stationary night blindness
• GRM6-related disorder
• Leber congenital amaurosis

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)

1.17

gnomAD pLI

0

gnomAD missense Z

-0.51

DepMap mean gene effect

0.01

DepMap dependency class

selective

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

• chemical synaptic transmission
• detection of light stimulus involved in visual perception
• G protein-coupled glutamate receptor signaling pathway
• gene expression
• locomotory behavior
• positive regulation of calcium ion import across plasma membrane
• regulation of synaptic transmission, glutamatergic
• retina development in camera-type eye
• synapse assembly
• detection of visible light

Molecular functions

• adenylate cyclase inhibiting G protein-coupled glutamate receptor activity
• G protein-coupled receptor activity
• glutamate receptor activity
• protein homodimerization activity

Cellular components

• dendrite
• endoplasmic reticulum membrane
• Golgi membrane
• plasma membrane
• synapse
• new growing cell tip

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 6

KeywordsUniProt

• Cell membrane
• Cell projection
• Congenital stationary night blindness
• Disulfide bond
• Endoplasmic reticulum
• G-protein coupled receptor
• Glycoprotein
• Golgi apparatus
• Membrane
• Receptor
• Sensory transduction
• Signal
• Transducer
• Transmembrane
• Transmembrane helix
• Vision

InteractionsUniProt · HPA

Protein binding partners of GRM6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GPR179
• NYX
• TRPM1