GRM2

Protein identityUniProt · HPA

UniProt accession

Q14416

Gene

GRM2

Ensembl

ENSG00000164082

Chromosome

3

Canonical length

872 aa

Protein class

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

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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

Canonical amino-acid sequenceUniProt

872 residues, UniProt reviewed canonical sequence.

>Q14416|GRM2
     1  MGSLLALLAL LLLWGAVAEG PAKKVLTLEG DLVLGGLFPV HQKGGPAEDC GPVNEHRGIQ
    61  RLEAMLFALD RINRDPHLLP GVRLGAHILD SCSKDTHALE QALDFVRASL SRGADGSRHI
   121  CPDGSYATHG DAPTAITGVI GGSYSDVSIQ VANLLRLFQI PQISYASTSA KLSDKSRYDY
   181  FARTVPPDFF QAKAMAEILR FFNWTYVSTV ASEGDYGETG IEAFELEARA RNICVATSEK
   241  VGRAMSRAAF EGVVRALLQK PSARVAVLFT RSEDARELLA ASQRLNASFT WVASDGWGAL
   301  ESVVAGSEGA AEGAITIELA SYPISDFASY FQSLDPWNNS RNPWFREFWE QRFRCSFRQR
   361  DCAAHSLRAV PFEQESKIMF VVNAVYAMAH ALHNMHRALC PNTTRLCDAM RPVNGRRLYK
   421  DFVLNVKFDA PFRPADTHNE VRFDRFGDGI GRYNIFTYLR AGSGRYRYQK VGYWAEGLTL
   481  DTSLIPWASP SAGPLPASRC SEPCLQNEVK SVQPGEVCCW LCIPCQPYEY RLDEFTCADC
   541  GLGYWPNASL TGCFELPQEY IRWGDAWAVG PVTIACLGAL ATLFVLGVFV RHNATPVVKA
   601  SGRELCYILL GGVFLCYCMT FIFIAKPSTA VCTLRRLGLG TAFSVCYSAL LTKTNRIARI
   661  FGGAREGAQR PRFISPASQV AICLALISGQ LLIVVAWLVV EAPGTGKETA PERREVVTLR
   721  CNHRDASMLG SLAYNVLLIA LCTLYAFKTR KCPENFNEAK FIGFTMYTTC IIWLAFLPIF
   781  YVTSSDYRVQ TTTMCVSVSL SGSVVLGCLF APKLHIILFQ PQKNVVSHRA PTSRFGSAAA
   841  RASSSLGQGS GSQFVPTVCN GREVVDSTTS SL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GRM2 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)

0.28

Highest tissue expression

4.6 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for GRM2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.49

gnomAD pLI

0.12

gnomAD missense Z

2.37

DepMap mean gene effect

-0.12

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

• behavioral response to nicotine
• cellular response to stress
• chemical synaptic transmission
• G protein-coupled glutamate receptor signaling pathway
• gene expression
• glutamate secretion
• intracellular glutamate homeostasis
• long-term synaptic depression
• negative regulation of adenylate cyclase activity
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• presynaptic modulation of chemical synaptic transmission
• regulation of dopamine secretion
• regulation of glutamate secretion
• regulation of response to drug
• regulation of synaptic transmission, glutamatergic
• response to cocaine

Molecular functions

• calcium channel regulator activity
• G protein-coupled receptor activity
• glutamate receptor activity
• group II metabotropic glutamate receptor activity
• scaffold protein binding

Cellular components

• astrocyte projection
• axon
• dendrite
• glutamatergic synapse
• plasma membrane
• postsynaptic membrane
• presynaptic 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 2

KeywordsUniProt

• Cell membrane
• Cell projection
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Membrane
• Receptor
• Signal
• Synapse
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GRM2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HTR2A
• TAMALIN
• TFRC
• ACE2