| Tchem | Metabotropic glutamate receptor 2 |
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. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.
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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Comments
| Disease | Target Count |
|---|---|
| Schizophrenia | 503 |
| Amphetamine-Related Disorders | 74 |
| Epilepsy, Temporal Lobe | 23 |
| Psychoses, Substance-Induced | 17 |
| Disease | Target Count | P-value |
|---|---|---|
| posterior fossa group A ependymoma | 1511 | 1.4e-10 |
| pediatric high grade glioma | 2712 | 2.5e-07 |
| pilocytic astrocytoma | 3086 | 2.7e-07 |
| glioblastoma | 5572 | 5.3e-07 |
| atypical teratoid / rhabdoid tumor | 4369 | 1.2e-05 |
| primitive neuroectodermal tumor | 3031 | 3.0e-03 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Cocaine dependence | 24 | 4.117 | 2.1 |
| Epilepsy | 346 | 3.871 | 1.9 |
| Parkinson's disease | 364 | 3.357 | 1.7 |
| Major Depressive Disorder | 106 | 3.356 | 1.7 |
| Toxic encephalopathy | 131 | 3.041 | 1.5 |
| Disease | log2 FC | p |
|---|---|---|
| posterior fossa group A ependymoma | -1.300 | 1.4e-10 |
| glioblastoma | -1.600 | 5.3e-07 |
| atypical teratoid / rhabdoid tumor | -1.500 | 1.2e-05 |
| primitive neuroectodermal tumor | -1.200 | 3.0e-03 |
| pediatric high grade glioma | -1.300 | 2.5e-07 |
| pilocytic astrocytoma | -1.300 | 2.7e-07 |
GNAT3
GRM8
F2RL2
P2RY10
CCL21
CXCL11
NPFF
GRM6
CCL25
CCL16
MLNR
HCRT
HCRTR1
HCRTR2
CXCL13
S1PR2
UTS2
NTSR2
S1PR4
F2
OXT
AVP
PENK
PDYN
PPY
NPY
PPBP
PF4
CXCL10
APP
NMB
NPS
SAA1
ADORA3
PYY
CXCL8
MLN
CCL5
ADRA2C
CXCL2
CXCL3
TAC1
PMCH
TRH
TACR2
TBXA2R
TACR1
PTAFR
ACKR3
F2R
NPY1R
HTR2C
NMBR
TACR3
OXTR
SSTR1
SSTR2
NTSR1
NTS
SSTR4
CXCR5
SSTR3
TRHR
PTGER1
SSTR5
OPRM1
AVPR1A
OPRD1
OPRK1
OPRL1
P2RY2
GRM5
CCR2
CXCL5
PTGFR
PTGER3
LPAR6
P2RY1
AVPR1B
XCL1
MTNR1A
CXCL12
NMU
PIK3CG
NPY2R
MTNR1B
CXCR3
NPY4R
P2RY4
CCR9
F2RL1
CCL23
PROK1
TAS2R38
TAS2R39
TAS2R40
TAS2R41
TAS2R43
TAS2R31
TAS2R45
TAS2R46
TAS2R30
TAS2R19
TAS2R20
TAS2R50
TAS2R60
GNG2
CXCR4
SST
CCL20
CXCL6
QRFP
PLCB2
PLCB3
CXCL9
PNOC
GRM7
GRM3
GRM4
P2RY6
P2RY14
NPY5R
NMS
GPRC6A
PIK3R6
NPSR1
UTS2B
TAS2R42
MT-RNR2
GPR65
NPW
PROKR2
NPB
PROKR1
HCAR2
OXER1
RXFP4
RLN3
PIK3R5
ARHGEF1
KISS1R
MCHR2
P2RY11
QRFPR
OXGR1
F2RL3
LPAR4
CCL19
P2RY13
SUCNR1
HCAR1
NMUR2
NPFFR1
LPAR5
S1PR5
P2RY12
CXCL16
NMUR1
PROK2
PLCB1
CCL28
HEBP1
RXFP3
TAS2R16
TAS2R14
TAS2R13
TAS2R10
TAS2R9
TAS2R8
TAS2R7
TAS2R5
TAS2R4
TAS2R3
TAS2R1
ARHGEF12
XCL2
GHRL
TAC3
OPN4
UTS2R
GPR132
GPR55
CCL27
NPFFR2
CHEMBL593745
pEC50 7.00
CHEMBL608103
pEC50 7.00
CHEMBL604993
pEC50 7.00
CHEMBL322465
pEC50 7.00
CHEMBL3616850
pKi 7.02
CHEMBL364324
pEC50 7.03
CHEMBL3616852
pEC50 7.06
CHEMBL323541
pEC50 7.06
CHEMBL3765537
pEC50 7.07
CHEMBL325140
pKi 7.07
CHEMBL8759
pKi 7.07
CHEMBL3616849
pKi 7.07
CHEMBL1094763
pEC50 7.09
CHEMBL3764024
pEC50 7.09
CHEMBL3764820
pEC50 7.10
CHEMBL593744
pEC50 7.10
CHEMBL605836
pEC50 7.10
CHEMBL1774231
pEC50 7.12
CHEMBL3616859
pEC50 7.13
CHEMBL105065
pEC50 7.14
| PMID | Text | |
|---|---|---|
| 26758213 | Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. | |
| 26589404 | this work offers new insights into the functioning of the mGlu2 receptor, which might contribute to the development of new and improved PAMs | |
| 25571949 | Study furthers our understanding of positive allosteric modulation of the mGlu2 receptor and can contribute to improved future design of mGlu2 modulators. | |
| 25150943 | Results demonstrate no changes in expression and density of both 5-HT2AR and mGlu2/3R in the postmortem prefrontal cortex of subjects with major depressive disorder under basal conditions; antidepressant treatment induces a decrease in 5-HT2AR density | |
| 24949866 | Findings suggest that mGluR2/3 and mGluR5s are unaltered in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia | |
| 23407939 | Human anterior cingulate cortex from alcoholic patients shows a significant reduction in mGluR(2) transcripts compared to control subjects | |
| 23149219 | the promoter methylation of the GMR2 and GMR5 genes greatly decreased the risk of schizophrenia, and the expression level of the GRM2, GRM5, and GRIA3 genes increased significantly in patients in comparison to healthy controls. | |
| 23129762 | Three residues located at the intracellular end of transmembrane domain four are necessary for the mGlu2 receptor binding to 5TR2A. | |
| 22988116 | Only full-length dimeric mGlu2 activates G protein upon glutamate binding. | |
| 22870276 | the structural properties for the H8 domain of the mGluR2 receptor; H8 behaves as a sensor of cholesterol concentration. | |
| 21881873 | data support the idea that glutamate release in the vental tegmental area(VTA) is critically involved in cocaine-induced reinstatement; loss of mGluR2/3-mediated regulation of glutamate release in the VTA may critically contribute to the risk of relapse | |
| 21173788 | Suggest a genetic association exists between SNPs in several genes, such as HTR2A and NRG1, and response to mGlu2/3 agonist LY2140023 treatment in schizophrenia. | |
| 20211215 | Our results suggested that GRM2 may play a role in the pathophysiology of methamphetamine-induced psychosis but not schizophrenia in the Japanese population | |
| 20211215 | Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) | |
| 19945495 | This study demonistrated that the level of metabotropic glutamate receptor 2/3 is elevated in the prefrontal cortex in patient of major depression disorder. | |
| 19635471 | Our findings suggest that disruption of glutamate receptors like NMDAR1 and mGluR2 at the Shank-postsynaptic platform could contribute to destruction of the postsynaptic density which underlies the synaptic dysfunction and loss in Alzheimer's disease. | |
| 19402024 | The glutamate receptor metabotropic 2 mutants with increased structural flexibility at this position, which is crucial for pocket closure, were clearly preferred. | |
| 19386277 | No association is detected between GRM2 and major depressive disorder or bipolar disorder in an allele/genotype-wise or haplotype-wise analysis of Japanese patients. | |
| 19386277 | Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) | |
| 19367581 | Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) | |
| 19156168 | Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) | |
| 19086053 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19026996 | findings show that the activation of mGluR2 leads to the activation of extracellular signal-related kinase pathways | |
| 18853337 | The expression of mGluR2, 3 in DA cells provide a mechanism for glutamate to modulate dopamine release in the human brain and this species-specific difference may be critical to understanding rodent models in schizophrenia. | |
| 18297054 | In post-mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis | |
| 16678921 | The objective of this study was to assess the effects of the mGlu2/3 receptor agonist LY404039 (LY) on operant EtOH self-administration during alcohol seeking pavlovian spontaneous recovery, alcohol relapse, and maintenance responding for alcohol. | |
| 15837331 | Authors have identified and synthesized a brain penetrant propanoic acid as an allosteric potentiator of the metabotropic glutamate receptor 2. | |
| 15330338 | Stimulation of glial mGluR2 through mediators present in the cerebrospinal fluid may contribute to glial proliferation and astrogliosis in amyotrophic lateral sclerosis. | |
| 15246118 | Reduction of mGluR2 immunopositive product in the stratum lacunosum moleculare of hippocampal CA1 is a consequence of neuronal loss in either the entorhinal cortex or CA1 area of the hippocampus. | |
| 11897108 | The presynaptic group 2 metabotropic glutamate receptor reduces stimulated and spontaneous transmitter release in the dentate gyrus. | |
| 11840499 | Mapped to Chromosome 3p21.1 - p21.2 and has 5 exons ranging from 74 - 1076 bp. | |
| 11641422 | Ser-148 and Arg-183 may be important for the 3D structure and/or are involved in closure of the domain. Asp-146 is involved in differential binding properties of mGlur2. | |
| 11317221 | Observational study of gene-disease association. (HuGE Navigator) |
MGSLLALLALLLLWGAVAEGPAKKVLTLEGDLVLGGLFPVHQKGGPAEDCGPVNEHRGIQRLEAMLFALD 1 - 70 RINRDPHLLPGVRLGAHILDSCSKDTHALEQALDFVRASLSRGADGSRHICPDGSYATHGDAPTAITGVI 71 - 140 GGSYSDVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFFQAKAMAEILRFFNWTYVSTV 141 - 210 ASEGDYGETGIEAFELEARARNICVATSEKVGRAMSRAAFEGVVRALLQKPSARVAVLFTRSEDARELLA 211 - 280 ASQRLNASFTWVASDGWGALESVVAGSEGAAEGAITIELASYPISDFASYFQSLDPWNNSRNPWFREFWE 281 - 350 QRFRCSFRQRDCAAHSLRAVPFEQESKIMFVVNAVYAMAHALHNMHRALCPNTTRLCDAMRPVNGRRLYK 351 - 420 DFVLNVKFDAPFRPADTHNEVRFDRFGDGIGRYNIFTYLRAGSGRYRYQKVGYWAEGLTLDTSLIPWASP 421 - 490 SAGPLPASRCSEPCLQNEVKSVQPGEVCCWLCIPCQPYEYRLDEFTCADCGLGYWPNASLTGCFELPQEY 491 - 560 IRWGDAWAVGPVTIACLGALATLFVLGVFVRHNATPVVKASGRELCYILLGGVFLCYCMTFIFIAKPSTA 561 - 630 VCTLRRLGLGTAFSVCYSALLTKTNRIARIFGGAREGAQRPRFISPASQVAICLALISGQLLIVVAWLVV 631 - 700 EAPGTGKETAPERREVVTLRCNHRDASMLGSLAYNVLLIALCTLYAFKTRKCPENFNEAKFIGFTMYTTC 701 - 770 IIWLAFLPIFYVTSSDYRVQTTTMCVSVSLSGSVVLGCLFAPKLHIILFQPQKNVVSHRAPTSRFGSAAA 771 - 840 RASSSLGQGSGSQFVPTVCNGREVVDSTTSSL 841 - 872 //
| PMID | Year | Title | |
|---|---|---|---|
| 26758213 | 2016 | Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. | |
| 26589404 | 2016 | Molecular mechanism of positive allosteric modulation of the metabotropic glutamate receptor 2 by JNJ-46281222. | |
| 25571949 | 2015 | Molecular determinants of positive allosteric modulation of the human metabotropic glutamate receptor 2. | |
| 25416956 | 2014 | A proteome-scale map of the human interactome network. | |
| 25150943 | 2014 | Evaluation of 5-HT2A and mGlu2/3 receptors in postmortem prefrontal cortex of subjects with major depressive disorder: effect of antidepressant treatment. | |
| 24949866 | 2014 | Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics. | |
| 24080311 | 2014 | Glutamate receptors and the regulation of steroidogenesis in the human adrenal gland: the metabotropic pathway. | |
| 23407939 | 2013 | Rescue of infralimbic mGluR2 deficit restores control over drug-seeking behavior in alcohol dependence. | |
| 23149219 | 2013 | Evaluation of hypermethylation and expression pattern of GMR2, GMR5, GMR8, and GRIA3 in patients with schizophrenia. | |
| 23129762 | 2012 | Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A·mGlu2) receptor heteromerization and its psychoactive behavioral function. | |
| 22988116 | 2012 | Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling. | |
| 22870276 | 2012 | Membrane-sensitive conformational states of helix 8 in the metabotropic Glu2 receptor, a class C GPCR. | |
| 22300836 | 2012 | Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. | |
| 21881873 | 2012 | Regulation of cocaine-induced reinstatement by group II metabotropic glutamate receptors in the ventral tegmental area. | |
| 21173788 | 2012 | Pharmacogenetic analysis of the mGlu2/3 agonist LY2140023 monohydrate in the treatment of schizophrenia. | |
| 20211215 | 2010 | Association analysis of GRM2 and HTR2A with methamphetamine-induced psychosis and schizophrenia in the Japanese population. | |
| 19945495 | 2010 | Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression. | |
| 19635471 | 2009 | Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease. | |
| 19402024 | 2009 | Mutagenesis and molecular modeling of the orthosteric binding site of the mGlu2 receptor determining interactions of the group II receptor antagonist (3)H-HYDIA. | |
| 19386277 | 2009 | Association analysis of group II metabotropic glutamate receptor genes (GRM2 and GRM3) with mood disorders and fluvoxamine response in a Japanese population. | |
| 19367581 | 2010 | Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population. | |
| 19156168 | 2009 | Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. | |
| 19086053 | 2009 | Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment. | |
| 19026996 | 2009 | The effect of mGluR2 activation on signal transduction pathways and neuronal cell survival. | |
| 18853337 | 2008 | Metabotropic glutamate receptor 2 and 3 gene expression in the human prefrontal cortex and mesencephalon in schizophrenia. | |
| 18297054 | 2008 | Identification of a serotonin/glutamate receptor complex implicated in psychosis. | |
| 16678921 | 2006 | The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats. | |
| 16344560 | 2006 | Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. | |
| 15837331 | 2005 | 3-(2-Ethoxy-4-{4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy}phenyl)propanoic acid: a brain penetrant allosteric potentiator at the metabotropic glutamate receptor 2 (mGluR2). | |
| 15489334 | 2004 | The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | |
| 15330338 | 2004 | Glial proliferation and metabotropic glutamate receptor expression in amyotrophic lateral sclerosis. | |
| 15246118 | Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus. | ||
| 12477932 | 2002 | Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. | |
| 11641422 | 2001 | Identification of essential residues involved in the glutamate binding pocket of the group II metabotropic glutamate receptor. | |
| 11317221 | 2001 | Structure and polymorphisms of the human metabotropic glutamate receptor type 2 gene (GRM2): analysis of association with schizophrenia. | |
| 9651375 | 1998 | GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain. | |
| 8863838 | 1996 | Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists. | |
| 8824806 | 1996 | Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. | |
| 7620613 | 1995 | Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2. |
