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mGlu1 receptor

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Target not currently curated in GtoImmuPdb

Target id: 289

Nomenclature: mGlu1 receptor

Family: Metabotropic glutamate receptors

Contents:

Gene and Protein Information Click here for help
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 1194 6q24.3 GRM1 glutamate metabotropic receptor 1 20,33,101
Mouse 7 1199 10 A1 Grm1 glutamate receptor, metabotropic 1 125
Rat 7 1199 1p13 Grm1 glutamate metabotropic receptor 1 44,77
Previous and Unofficial Names Click here for help
GPRC1A | metabotropic glutamate receptor 1 | wobl | MGLUR1 | SCAR13 | glutamate receptor, metabotropic 1 | glutamate receptor
Database Links Click here for help
Specialist databases
GPCRdb grm1_human (Hs), grm1_mouse (Mm), grm1_rat (Rn)
Other databases
Alphafold Q13255 (Hs), P97772 (Mm), P23385 (Rn)
ChEMBL Target CHEMBL3772 (Hs), CHEMBL2892 (Mm), CHEMBL4477 (Rn)
Ensembl Gene ENSG00000152822 (Hs), ENSMUSG00000019828 (Mm), ENSRNOG00000068415 (Rn), ENSRNOG00000014290 (Rn)
Entrez Gene 2911 (Hs), 14816 (Mm), 24414 (Rn)
Human Protein Atlas ENSG00000152822 (Hs)
KEGG Gene hsa:2911 (Hs), mmu:14816 (Mm), rno:24414 (Rn)
OMIM 604473 (Hs)
Orphanet ORPHA327283 (Hs)
Pharos Q13255 (Hs)
RefSeq Nucleotide NM_001278067 (Hs), NM_001278066 (Hs), NM_001278064 (Hs), NM_001278065 (Hs), NM_016976 (Mm), NM_001114333 (Mm), NM_017011 (Rn), NM_001114330 (Rn)
RefSeq Protein NP_001264995 (Hs), NP_001264994 (Hs), NP_001264996 (Hs), NP_001264993 (Hs), NP_001107805 (Mm), NP_058672 (Mm), NP_001107802 (Rn), NP_058707 (Rn)
UniProtKB Q13255 (Hs), P97772 (Mm), P23385 (Rn)
Wikipedia GRM1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of metabotropic glutamate receptor subtype 1 complexed with glutamate
PDB Id:  1EWK
Resolution:  2.2Å
Species:  Rat
References:  57
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of metabotropic glutamate receptor subtype 1 ligand free form II
PDB Id:  1EWV
Resolution:  4.0Å
Species:  Rat
References:  57
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Metabotropic Glutamate Receptor Subtype 1 Complexed with Glutamate and Gadolinium Ion
PDB Id:  1ISR
Resolution:  4.0Å
Species:  Rat
References:  114
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Metabotropic Glutamate Receptor Subtype 1 Complexed with an antagonist
PDB Id:  1ISS
Resolution:  3.3Å
Species:  Rat
References:  114
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of metabotropic glutamate receptor subtype 1 ligand free form 1
PDB Id:  1EWT
Resolution:  3.7Å
Species:  Rat
References:  57
Image of receptor 3D structure from RCSB PDB
Description:  Metabotropic glutamate receptor mGluR1 complexed with LY341495 antagonist
PDB Id:  3KS9
Ligand:  LY341495
Resolution:  1.9Å
Species:  Human
References: 
Image of receptor 3D structure from RCSB PDB
Description:  Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator.
PDB Id:  4OR2
Ligand:  FITM
Resolution:  2.8Å
Species:  Human
References:  119
Natural/Endogenous Ligands Click here for help
L-glutamic acid
Comments: Other endogenous ligands include L-aspartic acid, L-serine-O-phosphate, NAAG and L-cysteine sulphinic acid

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]quisqualate Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Full agonist 7.5 – 7.7 pKd 59,71
⤷ pKd 7.5 – 7.7 [59,71]
quisqualate Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 7.5 – 8.0 pKi 59,83
⤷ pKi 7.5 – 8.0 [59,83]
L-glutamic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 6.4 – 6.5 pKi 59,83
⤷ pKi 6.4 – 6.5 [59,83]
ibotenic acid Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.9 – 6.4 pKi 83,112
⤷ pKi 5.9 – 6.4 [83,112]
(1S,3R)-ACPD Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 5.5 – 6.1 pKi 59,83,112
⤷ pKi 5.5 – 6.1 [59,83,112]
3,5-DHPG Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.8 pKi 59
⤷ pKi 5.8 [59]
L-CCG-I Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.6 pKi 83
⤷ pKi 5.6 [83]
L-glutamic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 4.8 – 5.0 pEC50 87
⤷ pEC50 4.8 – 5.0 [87]
(S)-3HPG Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 4.9 pIC50 83
⤷ pIC50 4.9 [83]
View species-specific agonist tables
Agonist Comments
Values indicated are those determined from binding studies on recombinant mGlu1a receptors. Further information on agonist pharmacology as based on functional assays can be found in [95].

So far no differences in the agonist pharmacological profile has been reported between the rat and human mGlu1 receptors using functional assays.

The best characterized agonists of the ionotropic glutamate receptors, AMPA, NMDA and kainate are inactive on mGlu1. Although several splice variants of mGlu1 have been identified (see below), all are likely to have an identical agonist pharmacology since they possess an indentical agonist binding site.

The agonist binding site is located in the large extracellular domain of this receptor, that retains its ability to bind ligands when produced as a soluble protein. The structure of this binding domain has been solved [57,114]. This domain is formed of two lobes, and agonists bind in the cleft between the two lobes. Agonists likely stabilize a closed form of this domain, whereas antagonists prevent closure. Functional importance of critical residues involved in agonist action has been confirmed by mutagenesis studies [84,93].

Cations such as Ca2+ have been proposed to directly activate mGlu1 receptors [28,56,109]. However, it is still unclear whether this is a direct agonist effect or if this is due to a potentiation of ambient glutamate produced by the cells expressing the recombinant receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AIDA Small molecule or natural product Hs Antagonist 4.2 pA2 82
⤷ pA2 4.2 [82]
[11C]JNJ-16567083 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Antagonist 9.1 pKi 45
⤷ pKi 9.1 (Ki 8.7x10-10 M) [45]
LY341495 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.8 pKi 52
⤷ pKi 7.8 [52]
(S)-4C3HPG Small molecule or natural product Hs Antagonist 5.8 – 6.0 pKi 59,83
⤷ pKi 5.8 – 6.0 [59,83]
LY367385 Small molecule or natural product Rn Antagonist 5.9 pKi 59
⤷ pKi 5.9 (Ki 1.26x10-6 M) [59]
(S)-4CPG Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.4 pKi 59
⤷ pKi 5.4 [59]
DCG-IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 4.1 pKi 83
⤷ pKi 4.1 [83]
AIDA Small molecule or natural product Rn Antagonist 4.0 pKi 59
⤷ pKi 4.0 [59]
(+)-MCPG Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 3.8 pKi 59
⤷ pKi 3.8 [59]
3-MATIDA Small molecule or natural product Rn Antagonist 5.2 pIC50 81
⤷ pIC50 5.2 (IC50 6.3x10-6 M) [81]
LY367385 Small molecule or natural product Hs Antagonist 5.1 pIC50 15
⤷ pIC50 5.1 (IC50 8.8x10-6 M) [15]
(S)-TBPG Small molecule or natural product Rn Antagonist 4.2 pIC50 19
⤷ pIC50 4.2 (IC50 6.89x10-5 M) [19]
(S)-(+)-CBPG Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.2 pIC50 72
⤷ pIC50 4.2 (IC50 6.7x10-5 M) [72]
View species-specific antagonist tables
Antagonist Comments
Indicated affinities were determined by displacement studies of [3H]quisqualate bound on HEK cell membranes expressing a recombinant rat mGlu1 (except for LY341495 value determined from functional studies). More information on agonist potencies determined from functional studies can be obtained from [95]. So far no differences have been reported for the antagonist affinities between the rat and the human receptor. Although LY367385 and AIDA have been shown to specifically antagonize mGlu1 receptors versus mGlu5, both compounds are able to displace bound [3H]quisqualate to mGlu5 (see [95]).
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VU0483605 Small molecule or natural product N/A Positive 6.0 pKB 41
⤷ pKB 6.0 [41]
[3H]R214127 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Negative 9.0 pKd 59
⤷ pKd 9.0 [59]
[3H]EM-TBPC Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Positive 8.2 pKd 71
⤷ pKd 8.2 [71]
[3H]YM298198 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 7.5 pKd 55
⤷ pKd 7.5 (Kd 3.2x10-8 M) [55]
BAY 367620 Small molecule or natural product Rn Negative 9.5 pKi 11
⤷ pKi 9.5 (Ki 3.4x10-10 M) [11]
compound 23c [PMID: 17929793] Small molecule or natural product Rn Negative 9.4 pKi 120
⤷ pKi 9.4 (Ki 4x10-10 M) [120]
[11C]MMTP Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 9.2 pKi 90
⤷ pKi 9.2 (Ki 6x10-10 M) [90]
[18F]FITM Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 9.1 pKi 121
⤷ pKi 9.1 (Ki 8.7x10-10 M) [121]
compound 11c [PMID: 17929793] Small molecule or natural product Rn Negative 9.0 pKi 120
⤷ pKi 9.0 (Ki 1x10-9 M) [120]
NPS2390 Small molecule or natural product Rn Negative 8.9 pKi 59
⤷ pKi 8.9 [59]
R214127 Small molecule or natural product Rn Negative 8.9 pKi 59
⤷ pKi 8.9 [59]
JNJ-16567083 Small molecule or natural product Rn Negative 8.9 pKi 45
⤷ pKi 8.9 (Ki 1.4x10-9 M) [45]
compound 23h [PMID: 17929793] Small molecule or natural product Rn Negative 8.8 pKi 120
⤷ pKi 8.8 (Ki 1.5x10-9 M) [120]
compound 23e [PMID: 17929793] Small molecule or natural product Rn Negative 8.8 pKi 120
⤷ pKi 8.8 (Ki 1.5x10-9 M) [120]
compound 11q [PMID: 19433355] Small molecule or natural product Rn Negative 8.5 pKi 92
⤷ pKi 8.5 (Ki 3.5x10-9 M) [92]
compound 9a [PMID: 22266036] Small molecule or natural product Hs Negative 8.4 pKi 6
⤷ pKi 8.4 (Ki 3.6x10-9 M) [6]
compound 22 [PMID: 17276684] Small molecule or natural product Hs Negative 8.4 pKi 21
⤷ pKi 8.4 (Ki 3.6x10-9 M) [21]
compound 11s [PMID: 19433355] Small molecule or natural product Rn Negative 8.3 pKi 92
⤷ pKi 8.3 (Ki 4.7x10-9 M) [92]
compound 12e [PMID: 22266036] Small molecule or natural product Rn Negative 8.3 pKi 6
⤷ pKi 8.3 (Ki 5.2x10-9 M) [6]
A-794278 Small molecule or natural product Rn Negative 8.3 pKi 124
⤷ pKi 8.3 (Ki 5.4x10-9 M) [124]
FITM Small molecule or natural product Ligand has a PDB structure Rn Negative 8.3 pKi 31
⤷ pKi 8.3 (Ki 5.4x10-9 M) [31]
Description: Measured using rat brain homogenate in a competition binding assay displacing [18F}-FITM.
compound 27 [PMID: 20346665] Small molecule or natural product Rn Negative 8.1 pKi 91
⤷ pKi 8.1 (Ki 7.9x10-9 M) [91]
compound 29 [PMID: 17064898] Small molecule or natural product Rn Negative 8.0 pKi 86
⤷ pKi 8.0 (Ki 9.3x10-9 M) [86]
FPTQ Small molecule or natural product Rn Negative 7.9 pKi 30
⤷ pKi 7.9 (Ki 1.26x10-8 M) [30]
EM-TBPC Small molecule or natural product Rn Negative 7.8 pKi 71
⤷ pKi 7.8 (Ki 1.7x10-8 M) [71]
Ro67-7476 Small molecule or natural product Rn Positive 7.5 – 7.9 pKi 53
⤷ pKi 7.5 – 7.9 (Ki 3.16x10-8 – 1.26x10-8 M) [53]
YM-202074 Small molecule or natural product Rn Negative 7.7 pKi 54
⤷ pKi 7.7 (Ki 2x10-8 M) [54]
Ro01-6128 Small molecule or natural product Rn Positive 7.5 – 7.7 pKi 53
⤷ pKi 7.5 – 7.7 (Ki 3.16x10-8 – 1.99x10-8 M) [53]
compound 24 [PMID: 20346665] Small molecule or natural product Hs Negative 6.9 pKi 91
⤷ pKi 6.9 (Ki 1.15x10-7 M) [91]
compound 24 [PMID: 20346665] Small molecule or natural product Rn Negative 6.9 pKi 91
⤷ pKi 6.9 (Ki 1.15x10-7 M) [91]
compound 2f [PMID: 17532216] Small molecule or natural product Hs Negative 6.9 pKi 118
⤷ pKi 6.9 (Ki 1.27x10-7 M) [118]
LY456066 Small molecule or natural product Rn Negative 6.8 pKi 32
⤷ pKi 6.8 (Ki 1.43x10-7 M) [32]
CPCCOEt Small molecule or natural product Click here for species-specific activity table Rn Negative 5.3 pKi 59
⤷ pKi 5.3 [59]
Ro67-4853 Small molecule or natural product Rn Positive 5.1 pKi 53
⤷ pKi 5.1 (Ki 7.94x10-6 M) [53]
Ro0711401 Small molecule or natural product Rn Positive 7.3 pEC50 117
⤷ pEC50 7.3 (EC50 5.6x10-8 M) [117]
compound 3a [PMID: 16099654] Small molecule or natural product Rn Positive 7.2 pEC50 116
⤷ pEC50 7.2 (EC50 6.5x10-8 M) [116]
compound 4b [PMID: 16099654] Small molecule or natural product Rn Positive 7.2 pEC50 116
⤷ pEC50 7.2 (EC50 6.5x10-8 M) [116]
VU0483605 Small molecule or natural product Hs Positive 6.4 pEC50 13
⤷ pEC50 6.4 (EC50 3.9x10-7 M) [13]
VU-71 Small molecule or natural product Rn Positive 5.6 pEC50 116
⤷ pEC50 5.6 (EC50 2.4x10-6 M) [116]
CPCCOEt Small molecule or natural product Click here for species-specific activity table Rn Negative 5.3 pEC50 60
⤷ pEC50 5.3 (EC50 5x10-6 M) [60]
compound 11q [PMID: 19433355] Small molecule or natural product Hs Negative 9.1 pIC50 92
⤷ pIC50 9.1 (IC50 9x10-10 M) [92]
A-841720 Small molecule or natural product Rn Negative 9.0 – 9.0 pIC50 123-124
⤷ pIC50 9.0 – 9.0 (IC50 1.05x10-9 – 1x10-9 M) [123-124]
JNJ16259685 Small molecule or natural product Hs Negative 8.9 pIC50 63
⤷ pIC50 8.9 (IC50 1.21x10-9 M) [63]
compound 23i [PMID: 17929793] Small molecule or natural product Hs Negative 8.9 pIC50 120
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [120]
compound 24 [PMID: 20346665] Small molecule or natural product Hs Negative 8.7 pIC50 91
⤷ pIC50 8.7 (IC50 2.1x10-9 M) [91]
compound 11s [PMID: 19433355] Small molecule or natural product Hs Negative 8.7 pIC50 92
⤷ pIC50 8.7 (IC50 2.1x10-9 M) [92]
compound 23h [PMID: 17929793] Small molecule or natural product Hs Negative 8.7 pIC50 120
⤷ pIC50 8.7 (IC50 2.2x10-9 M) [120]
compound 23c [PMID: 17929793] Small molecule or natural product Hs Negative 8.6 pIC50 120
⤷ pIC50 8.6 (IC50 2.5x10-9 M) [120]
CFMTI Small molecule or natural product Hs Negative 8.6 pIC50 94
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [94]
compound 23e [PMID: 17929793] Small molecule or natural product Hs Negative 8.5 pIC50 120
⤷ pIC50 8.5 (IC50 2.9x10-9 M) [120]
A-794282 Small molecule or natural product Hs Negative 8.5 pIC50 122
⤷ pIC50 8.5 (IC50 3x10-9 M) [122]
compound 22 [PMID: 19289283] Small molecule or natural product Rn Negative 8.5 pIC50 73
⤷ pIC50 8.5 (IC50 3x10-9 M) [73]
[18F]MK-1312 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Negative 8.4 pIC50 43
⤷ pIC50 8.4 (IC50 3.6x10-9 M) [43]
MK-5435 Small molecule or natural product Hs Negative 8.4 pIC50 43
⤷ pIC50 8.4 (IC50 4.3x10-9 M) [43]
A-794282 Small molecule or natural product Rn Negative 8.3 pIC50 124
⤷ pIC50 8.3 (IC50 4.7x10-9 M) [124]
FTIDC Small molecule or natural product Rn Negative 8.3 pIC50 105
⤷ pIC50 8.3 (IC50 4.8x10-9 M) [105]
compound 11c [PMID: 17929793] Small molecule or natural product Hs Negative 8.3 pIC50 120
⤷ pIC50 8.3 (IC50 4.9x10-9 M) [120]
[18F]FITM Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Negative 8.3 pIC50 121
⤷ pIC50 8.3 (IC50 5.1x10-9 M) [121]
[18F]FPIT Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Negative 8.3 pIC50 29
⤷ pIC50 8.3 (IC50 5.4x10-9 M) [29]
FTIDC Small molecule or natural product Hs Negative 8.2 pIC50 105
⤷ pIC50 8.2 (IC50 5.8x10-9 M) [105]
compound 32 [PMID: 19289283] Small molecule or natural product Rn Negative 8.2 pIC50 73
⤷ pIC50 8.2 (IC50 6x10-9 M) [73]
compound 10i [PMID: 23084894] Small molecule or natural product Hs Negative 8.2 pIC50 10
⤷ pIC50 8.2 (IC50 6x10-9 M) [10]
compound 9a [PMID: 22266036] Small molecule or natural product Hs Negative 8.2 pIC50 6
⤷ pIC50 8.2 (IC50 6.3x10-9 M) [6]
compound 9n [PMID: 23084894] Small molecule or natural product Hs Negative 8.1 pIC50 10
⤷ pIC50 8.1 (IC50 7x10-9 M) [10]
YM-202074 Small molecule or natural product Rn Negative 8.1 pIC50 54
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [54]
compound 29 [PMID: 17064898] Small molecule or natural product Rn Negative 8.1 pIC50 86
⤷ pIC50 8.1 (IC50 9x10-9 M) [86]
[11C]MMTP Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Negative 8.0 pIC50 90
⤷ pIC50 8.0 (IC50 9.5x10-9 M) [90]
A-841720 Small molecule or natural product Hs Negative 8.0 pIC50 122
⤷ pIC50 8.0 (IC50 1x10-8 M) [122]
A-794278 Small molecule or natural product Hs Negative 8.0 pIC50 122
⤷ pIC50 8.0 (IC50 1x10-8 M) [122]
R214127 Small molecule or natural product Hs Negative 8.0 pIC50 59
⤷ pIC50 8.0 (IC50 1.04x10-8 M) [59]
compound 12e [PMID: 22266036] Small molecule or natural product Hs Negative 7.9 pIC50 6
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [6]
DM-PPP Small molecule or natural product Rn Negative 7.8 pIC50 80
⤷ pIC50 7.8 [80]
YM298198 Small molecule or natural product Rn Negative 7.8 pIC50 55
⤷ pIC50 7.8 [55]
3,5-dimethyl PPP Small molecule or natural product Rn Negative 7.8 pIC50 80
⤷ pIC50 7.8 (IC50 1.58x10-8 M) [80]
compound 3 [PMID: 12470711] Small molecule or natural product Rn Negative 7.8 pIC50 80
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [80]
compound 27 [PMID: 20346665] Small molecule or natural product Hs Negative 7.6 pIC50 91
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [91]
LY456066 Small molecule or natural product Hs Negative 7.6 pIC50 32
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [32]
BAY 367620 Small molecule or natural product Rn Negative 6.8 – 8.0 pIC50 11,59
⤷ pIC50 6.8 – 8.0 (IC50 1.58x10-7 – 1x10-8 M) [11,59]
A-850002 Small molecule or natural product Rn Negative 7.4 pIC50 124
⤷ pIC50 7.4 (IC50 4.09x10-8 M) [124]
A-850002 Small molecule or natural product Hs Negative 7.4 pIC50 122
⤷ pIC50 7.4 (IC50 4.3x10-8 M) [122]
CFMMC Small molecule or natural product Hs Negative 7.3 pIC50 32
⤷ pIC50 7.3 (IC50 5x10-8 M) [32]
cis-10 [PMID: 15771457] Small molecule or natural product Hs Negative 7.0 pIC50 69
⤷ pIC50 7.0 (IC50 9.4x10-8 M) [69]
VU0469650 Small molecule or natural product Hs Negative 7.0 pIC50 66
⤷ pIC50 7.0 (IC50 9.9x10-8 M) [66]
YM298198 Small molecule or natural product Hs Negative 6.9 pIC50 32
⤷ pIC50 6.9 (IC50 1.2x10-7 M) [32]
LY456236 Small molecule or natural product Hs Negative 6.9 pIC50 12
⤷ pIC50 6.9 (IC50 1.4x10-7 M) [12]
EM-TBPC Small molecule or natural product Rn Negative 6.9 pIC50 71
⤷ pIC50 6.9 (IC50 1.28x10-7 M) [71]
compound 22 [PMID: 17276684] Small molecule or natural product Rn Negative 6.8 pIC50 21
⤷ pIC50 6.8 (IC50 1.67x10-7 M) [21]
CPCCOEt Small molecule or natural product Hs Negative 5.2 – 5.8 pIC50 65
⤷ pIC50 5.2 – 5.8 (IC50 6.3x10-6 – 1.5x10-6 M) [65]
PHCCC Small molecule or natural product Click here for species-specific activity table Hs Positive - -
⤷
View species-specific allosteric modulator tables
Allosteric Modulator Comments
Values for Ro67-4853 and Ro67-7476 were determined by binding studies using [3H]R214127 binding [59] or from functional studies [11,53,65]. Among these allosteric regulators only NPS2390 is not mGlu1 selective, being also active as a negative allosteric modulator of mGlu5. Among the positive modulators, only Ro67-4853 is active on the human receptor [53]. The binding site of all allosteric regulators have been mapped within the 7 transmembrane domain of the receptor [11,53,65,71].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  The primary action of the mGlu1 is to activate PLC through stimulating Gq/11, resulting in the PIP2 breakdown which can be monitored as the production of inositol phosphate. The PIP2 breakdown causes the increases in the intracellular calcium concentration and the activation of the TRPC channels [39]. The primary transduction is observed both in cell lines and the native tissue expressing the mGlu1.
References:  3,17,25,88
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Gi/Go family
G protein independent mechanism 		Adenylyl cyclase stimulation
Adenylyl cyclase inhibition
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  Stimulation of adenylyl cyclase via mGlu1 has been reported in transfected cell lines [25] and suggested in neuronal cells [104]. Activation of the mGlu1 triggers the PTX-sensitive Gi/o signaling pathway in transfected cell lines, but its physiological role is unclear. The mGlu1 also induces the phospohrylation of the ERK in the G protein dependent and independent manner. In the latter case, the effects are mediated via beta-arrestin and dependent on the type of the ligands [23]. Activation of PLD has been reported in a cell line and native tissues [25,96]. The mGlu1 has been reported to activate the TRPC1 channels indepedently of G protein [51].
References:  3,17,25,88
Tissue Distribution Click here for help
Testes.
Species:  Human
Technique:  immunocytochemistry.
References:  103
Thymus, thymocytes, TC-1s thymic epithelial cell line.
Species:  Mouse
Technique:  RT-PCR.
References:  102
Peripheral unmyelinated sensory afferent terminals.
Species:  Mouse
Technique:  Immunoelectron microscopy.
References:  8
At the subcellular level, mGlu1 proteins were found in post-synaptic elements on the side of the post-synaptic density. Although some reports have suggested the presence of mGlu1 in pre-synaptic elements, this issue remains at present unresolved.
Species:  Rat
Technique:  immunocytochemistry.
References:  27,67-68
Olfactory bulb, stratum oriens of CA1 and polymorph layer of dentate gyrus in hippocampus, globus pallidus, thalamus, substantia nigra, superior colliculus, cerebellum > neocortex, striatum, amygdala, hypothalamus, medulla.
Species:  Rat
Technique:  Immunohistochemistry.
References:  74
Olfactory bulb, thalamic nuclei (anterodorsal, anteroventral, ventrolateral posterior, medial geniculate, nucleus gelatinosum) > lateral hypothalamus, island of Calleja, mammillary bodies, nucleus of Darkshevich, brainstem, cranial nuclei, ventral horn of the spinal cord.
Species:  Rat
Technique:  Immunohistochemistry.
References:  27
mGlu1(a): cerebellum, diencephalon, mesencephalon, olfactory bulb, brainstem.
mGlu1(b): cerebral cortex, septum, striatum.
Species:  Rat
Technique:  PCR.
References:  38
In the hippocampus, mGlu1(a) is located in non-principal neurones in all areas, including the oriens-alveus border of the CA1 field, whereas mGlu1(b) is expressed in principal cells of the CA3 field and dentate granule cells, but absent in the CA1 region.
Species:  Rat
Technique:  Immunohistochemistry.
References:  24
Purkinje cell bodies and dendrites, golgi neurones of the granular cell layer, hippocampus (interneurons of the striatum oriens and dentate hilar region).
Species:  Rat
Technique:  immunocytochemistry.
References:  38
mGlu1(b): magnocellular neurons of the neuroendocrine supraoptic, paraventricular and circuate nuclei, neuronal cell bodies of the retrochiasmatic, anterior commissural and paraventricular nuclei.
Species:  Rat
Technique:  immunocytochemistry.
References:  78
mGlu1(b) and mGlu1(c): Hippocampus: CA3 region > granule cells.
Absent in CA1 region.
Species:  Rat
Technique:  Immunohistochemistry.
References:  67
mGlu1(a): heart: nerve terminals, ganglion cells and elements of the conducting system.
Species:  Rat
Technique:  immunocytochemistry.
References:  35
Subpopulation of basal keratinocytes.
Species:  Rat
Technique:  immunocytochemistry.
References:  34
mGlu1(a) and mGlu1(b): circumvallate papillae (taste buds).
Species:  Rat
Technique:  RT-PCR, in situ hybridisation, immunocytochemistry.
References:  113
Testes.
Species:  Rat
Technique:  RT-PCR.
References:  103
Hippocampal dentate gyrus and CA2-3, cerebellar Purkinje cells.
Species:  Rat
Technique:  in situ hybridization.
References:  77
When examined at the electron microscopic level in the cerebellar cortex, mGlu(1b) was found at the same perisynaptic location as mGlu(1a).
Species:  Rat
Technique:  immunocytochemistry.
References:  79
Cerebellum, mitral and tufted cells of the olfactory bulb, hippocampus, lateral septum, thalamus, globus pallidus, entopendenuclear nucleus, ventral pallidum, magnocellular preoptic nucleus, substantia nigra, dorsal cochlear nucleus > dentate gyrus, striatum, islands of Calleja, superficial layers of the retrospinal, cingulate and entorhinal cortices, mammillary nuclei, red nucleus, superior colliculus.
Species:  Rat
Technique:  in situ hybridization.
References:  98
Cerebellar cortex.
Species:  Rat
Technique:  immunocytochemistry.
References:  46
Neostriatum, neocortex, hippocampus.
Species:  Rat
Technique:  in situ hybridization.
References:  50
Unipolar brush cells of cerebellum and cochlear nuclear complex.
Species:  Rat
Technique:  immunocytochemistry.
References:  48
Striatal neurons.
Species:  Rat
Technique:  Immunohistochemistry.
References:  107
Cerebellum, thalamus, dentate gyrus, medial central gray > CA3 region of the hippocampus and hypothalamus > basal ganglia, cortex.
Species:  Rat
Technique:  Radioligand binding.
References:  61
Retina.
Species:  Rat
Technique:  in situ hybridisation.
References:  40
GABAergic neurons of the cerebellar cortex, somatostatin/GABA-immunopositive cells in the neocortex and hippocampus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  5
Olfactory bulb, CA3 region of the hippocampus, dentate gyrus, globus pallidus, thalamic nuclei, medial geniculate nucleus, mammillary bodies, Darkshevich's nucleus, deep cerebellar nuclei, lateral vestibular nucleus, facial nucleus, spinal motor nucleus of the trigeminal nerve.
Species:  Rat
Technique:  in situ hybridisation.
References:  27
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of IP levels
Species:  Rat
Tissue:  HEK 293 cells
Response measured:  IP accumulation
References:  75
Measurement of Ca2+ levels in CHO cells transfected with the rat mGlu1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Ca2+ mobilisation.
References:  63
Measurement of IP levels in rat cerebellar granule cells expressing the native mGlu1 receptor.
Species:  Rat
Tissue:  Primary cultures of cerebellar granule cells.
Response measured:  IP accumulation.
References:  62
Measurement of intracellular Ca2+ levels and K+ conductance in rat dopamine neurons.
Species:  Rat
Tissue:  Dopamine neurons of the ventral tegmental area.
Response measured:  Mobilisation of Ca2+ and subsequent increase in K+ conductance.
References:  26
Measurement of IP levels in CHO cells transfected with the rat mGlu1.
Species:  Rat
Tissue:  CHO cells.
Response measured:  IP formation.
References:  97
Measurement of IP and Ca2+ levels in L929sA cells transfected with the human mGlu1 receptor.
Species:  Human
Tissue:  L929sA cells.
Response measured:  IP accumulation and Ca2+ mobilisation.
References:  60
mGlu1 induced current and intracellular Ca2+ levels
Species:  Mouse
Tissue:  Cultured cerebellar Purkinje neurons
Response measured:  mGlu1 induced current and Ca2+ mobilization
References:  106
Voltage-sensitivity of the mGlu1
Species:  Rat
Tissue:  Oocyte
Response measured:  Calcium induced Cl- current
References:  85
Measurement of IP, cAMP and arachidonic acid levels in CHO cells transfected with the rat mGlu1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  IP, cAMP, arachidonic acid formation and calcium mobilisation
References:  4,63,97
Physiological Functions Click here for help
Slow excitatory effect as well as inhibitory effects, depending on the channel activated or inhibited.
Species:  Rat
Tissue:  Dopamine neurons of the ventral tegmental area.
References:  26
mGlu1 at the periphery is involved in the sensation of inflamatory pain.
Species:  Mouse
Tissue:  Skin.
References:  8
Long-term depression (LTD).
Species:  Rat
Tissue:  Purkinje cells.
References:  97
Motor coordination, spacial learning, cerebellar long-term depression (LTD) and hippocampal mossy fibre long-term potentiation (LTP).
Species:  Mouse
Tissue:  In vivo.
References:  18
Long-term depression (LTD).
Species:  Mouse
Tissue:  In vivo.
References:  2
Excitatory synaptic transmission, long-term depression, short-term potentiation.
Species:  Mouse
Tissue:  Hippocampal slices.
References:  1
Normal synapse formation, synaptic plasticity and motor control.
Species:  Mouse
Tissue:  In vivo.
References:  47
Physiological Consequences of Altering Gene Expression Click here for help
Cerebellar ataxia.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  2,18,47
Disruption of prepulse inhibition.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  9
Loss of corticostriatal LTD.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  36
Ectopic expression of mGlu1 in melanocyte may cause melanoma
Species:  Mouse
Tissue: 
Technique:  Transgenesis; induced mutation.
References:  89
Persistent multiple climbing fiber innervation of cerebellar Purkinje cells.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  49,64
Context-specific deficit in associative learning.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  1
Impaired hippocampal LTP (long-term potentiation).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  1,18
Loss of LTD (long-term depression) at the parallel fibre-Purkinje cell synapse.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  2,18
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Grm1tm1Stl|Pcp2+|Pcp2tm1(tTA)23Atai|Tg(tetO-Grm1)7Atai Grm1tm1Stl/Grm1tm1Stl,Pcp2tm1(tTA)23Atai/Pcp2+,Tg(tetO-Grm1)7Atai/?
involves: 129S2/SvPas * C57BL/6N		 MGI:1351338  MGI:3715312  MGI:97508  MP:0004924 abnormal behavior PMID: 17270300 
Grm1tm1Stl Grm1tm1Stl/Grm1tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:1351338  MP:0001469 abnormal contextual conditioning behavior PMID: 7954802 
Grm1wobl Grm1wobl/Grm1wobl
C57BL/6Apb-Grm1/Apb		 MGI:1351338  MP:0002161 abnormal fertility/fecundity
Grm1rcw Grm1rcw/Grm1rcw
129S1/SvImJ		 MGI:1351338  MP:0001406 abnormal gait
Grm1tm1Stl|Pcp2+|Pcp2tm1(tTA)23Atai|Tg(tetO-Grm1)7Atai Grm1tm1Stl/Grm1tm1Stl,Pcp2tm1(tTA)23Atai/Pcp2+,Tg(tetO-Grm1)7Atai/?
involves: 129S2/SvPas * C57BL/6N		 MGI:1351338  MGI:3715312  MGI:97508  MP:0001406 abnormal gait PMID: 17270300 
Grm1rcw-2J Grm1rcw-2J/Grm1rcw-2J
either: B6(129X1)-Grm1/J or B6.129X1 Bax/J-Grm1/J		 MGI:1351338  MP:0001386 abnormal maternal nurturing
Grm1rcw-4J Grm1rcw-4J/Grm1rcw-4J
C57BL/6J-Grm1/GrsrJ		 MGI:1351338  MP:0001386 abnormal maternal nurturing
Grm1tm1Stl|Pcp2+|Pcp2tm1(tTA)23Atai|Tg(tetO-Grm1)7Atai Grm1tm1Stl/Grm1tm1Stl,Pcp2tm1(tTA)23Atai/Pcp2+,Tg(tetO-Grm1)7Atai/?
involves: 129S2/SvPas * C57BL/6N		 MGI:1351338  MGI:3715312  MGI:97508  MP:0001516 abnormal motor coordination/ balance PMID: 17270300 
Grm1tm1Nak Grm1tm1Nak/Grm1tm1Nak
involves: C57BL/6		 MGI:1351338  MP:0002272 abnormal nervous system electrophysiology PMID: 15305863 
Grm1rcw-4J Grm1rcw-4J/Grm1rcw-4J
C57BL/6J-Grm1/GrsrJ		 MGI:1351338  MP:0002272 abnormal nervous system electrophysiology
Grm1rcw-2J Grm1rcw-2J/Grm1rcw-2J
either: B6(129X1)-Grm1/J or B6.129X1 Bax/J-Grm1/J		 MGI:1351338  MP:0002566 abnormal sexual interaction
Grm1rcw-4J Grm1rcw-4J/Grm1rcw-4J
C57BL/6J-Grm1/GrsrJ		 MGI:1351338  MP:0002566 abnormal sexual interaction
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001463 abnormal spatial learning PMID: 7969468 
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001393 ataxia PMID: 7969468 
Grm1tm1Stl Grm1tm1Stl/Grm1tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:1351338  MP:0001393 ataxia PMID: 7954802 
Grm1rcw-2J Grm1rcw-2J/Grm1rcw-2J
either: B6(129X1)-Grm1/J or B6.129X1 Bax/J-Grm1/J		 MGI:1351338  MP:0001393 ataxia
Grm1rcw-3J Grm1rcw-3J/Grm1rcw-3J
C57BL/6J-Grm1/GrsrJ		 MGI:1351338  MP:0001393 ataxia
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001393 ataxia
Grm1nmf373 Grm1nmf373/Grm1nmf373
C57BL/6J-Grm1/J		 MGI:1351338  MP:0001393 ataxia
Grm1wobl Grm1wobl/Grm1wobl
C57BL/6Apb-Grm1/Apb		 MGI:1351338  MP:0001393 ataxia
Grm1rcw-4J Grm1rcw-4J/Grm1rcw-4J
C57BL/6J-Grm1/GrsrJ		 MGI:1351338  MP:0001393 ataxia
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0001393 ataxia PMID: 16964410 
Grm1rcw-2J Grm1rcw-2J/Grm1rcw-2J
either: B6(129X1)-Grm1/J or B6.129X1 Bax/J-Grm1/J		 MGI:1351338  MP:0001265 decreased body size
Grm1rcw-3J Grm1rcw-3J/Grm1rcw-3J
C57BL/6J-Grm1/GrsrJ		 MGI:1351338  MP:0001265 decreased body size
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001265 decreased body size
Grm1rcw-4J Grm1rcw-4J/Grm1rcw-4J
C57BL/6J-Grm1/GrsrJ		 MGI:1351338  MP:0001265 decreased body size
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0001265 decreased body size PMID: 16964410 
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001262 decreased body weight
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0010124 decreased bone mineral content
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0010121 decreased bone mineral density
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001417 decreased exploration in new environment PMID: 7969468 
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001505 hunched posture
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001402 hypoactivity
Grm1rcw Grm1rcw/Grm1rcw
129S1/SvImJ		 MGI:1351338  MP:0001525 impaired balance
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001524 impaired limb coordination
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001523 impaired righting response PMID: 7969468 
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0000005 increased brown adipose tissue amount PMID: 16964410 
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0000069 kyphoscoliosis PMID: 16964410 
Grm1rcw Grm1rcw/Grm1rcw
129S1/SvImJ		 MGI:1351338  MP:0001513 limb grasping
Grm1nmf373 Grm1nmf373/Grm1nmf373
C57BL/6J-Grm1/J		 MGI:1351338  MP:0001513 limb grasping
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0001925 male infertility PMID: 16964410 
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0000743 muscle spasm PMID: 16964410 
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0005287 narrow eye opening PMID: 16964410 
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0002083 premature death
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0001923 reduced female fertility PMID: 16964410 
Grm1tm1Stl Grm1tm1Stl/Grm1tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:1351338  MP:0001921 reduced fertility PMID: 7954802 
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001475 reduced long term depression PMID: 7969468 
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0001473 reduced long term potentiation PMID: 7969468 
Grm1tm1Stl Grm1tm1Stl/Grm1tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:1351338  MP:0001473 reduced long term potentiation PMID: 7954802 
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
Not Specified		 MGI:1351338  MP:0001473 reduced long term potentiation PMID: 12559117 
Grm1tm1Crpl Grm1tm1Crpl/Grm1tm1Crpl
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0000745 tremors PMID: 7969468 
Grm1tm1Stl Grm1tm1Stl/Grm1tm1Stl
involves: 129S2/SvPas * C57BL/6		 MGI:1351338  MP:0000745 tremors PMID: 7954802 
Grm1nmf373 Grm1nmf373/Grm1nmf373
C57BL/6J-Grm1/J		 MGI:1351338  MP:0000745 tremors
Grm1crv4 Grm1crv4/Grm1crv4
BALB/cPas-Grm1		 MGI:1351338  MP:0000745 tremors PMID: 16964410 
Grm1tm1Dgen Grm1tm1Dgen/Grm1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:1351338  MP:0000746 weakness
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Spinocerebellar ataxia, autosomal recessive 13; SCAR13
Synonyms: Autosomal recessive congenital cerebellar ataxia due to MGLUR1 deficiency [Orphanet: ORPHA324262]
OMIM: 614831
Orphanet: ORPHA324262
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
In-frame deletion Human N885del c.2652_2654del 3 bp exon 8 deletion 37
Splice site Human c.2660+2T>G Intron 8 37
Clinically-Relevant Mutations and Pathophysiology Comments
In patients with congenital cerebellar ataxia, the mutated receptor is predicted not to possess the 7 transmembrane domain and therefore to be nonfunctional.

Besides mutation, autoantibodies against the mGlu1 receptor have been reported in patients with paraneoplastic cerebellar ataxia [16,99].
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  mGlu1(b): This isoform is produced by the insertion of the 85 bp exon (exon IX), which contains an in-fram stop codon. It results in the replacement of the 313 C-terminal amino acids of mGlu1a by 20 different residues.
Amino acids:  906
Nucleotide accession:  NM_001278066
Protein accession:  NP_001264995
References:  101
Type:  Splice variant
Species:  Human
Description:  mGlu1(g): this isoform is produed by the addition of just one amino acid after the exon VIII/intron boundary. The 313 C-terminal amino acids of mGlu1a is displaced with 1 amino acid.
Amino acids:  887
References:  70
Type:  Splice variant
Species:  Human
Description:  mGlu1(h): mRNA of this isoform contains newly identified exons IXa and IXb. In the predicted protein, the 313 C-terminal amino acids of mGlu1a is displaced with different 10 amino acids.
Amino acids:  896
References:  22
Type:  Splice variant
Species:  Human
Description:  mGlu1(d): in this isoform, the 313 C-terminal amino acids of mGlu1a is displaced with 22 different residues
Amino acids:  908
Nucleotide accession:  NM_001278067
Protein accession:  NP_001264996
References:  42,58
Type:  Splice variant
Species:  Rat
Description:  mGlu1(b): in this form, the 313 C-terminal amino acids of the mGluR1(a) is displaced with 20 different residues, which results in the attenuation the G protein coupling and disrupts the protein-protein interaction with some molecules.
Amino acids:  906
Nucleotide accession:  NM_001114330
Protein accession:  NP_001107802
References:  14,108,110-111,115
Type:  Splice variant
Species:  Rat
Description:  mGlu1(d): this isoform is an alternative splicing valiant. The 313 C-terminal amino acids of mGlu1a is displaced with 26 different residues
Amino acids:  912
References:  7,76,100
Type:  Splice variant
Species:  Mouse
Description:  mGlu1(b): in this form, the 313 C-terminal amino acids of mGluR1(a) is displaced with 20 different residues.
Amino acids:  906
Nucleotide accession:  NM_001114333
Protein accession:  NP_001107805
References:  125
Type:  Splice variant
Species:  Mouse
Description:  mGlu1E55: this form results from the insertion of E55 exon containing an in-frame stop codon before the 7 TM region. The predicted protein is a soluble extracellular domain of mGlu1
Amino acids:  321
References:  125
Biologically Significant Variant Comments
In humans mGlu1, mGlu1(c) and mGlu1(e) have not been identified. The amino acid sequence of the mGlu1(f) is predicted to be same as the mGlu1(b).

Genomic data supports the existance of mGlu(1d) in mice
According to genomic sequences mGlu1e appears possible in rat but does not seem to be present in human genomic sequences.

References

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1. Aiba A, Chen C, Herrup K, Rosenmund C, Stevens CF, Tonegawa S. (1994) Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluR1 mutant mice. Cell, 79: 365-375. [PMID:7954802]

2. Aiba A, Kano M, Chen C, Stanton ME, Fox GD, Herrup K, Zwingman TA, Tonegawa S. (1994) Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice. Cell, 79 (2): 377-88. [PMID:7954803]

3. Anwyl R. (1999) Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Brain Res Rev, 29 (1): 83-120. [PMID:9974152]

4. Aramori I, Nakanishi S. (1992) Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron, 8 (4): 757-65. [PMID:1314623]

5. Baude A, Nusser Z, Roberts JD, Mulvihill E, McIlhinney RA, Somogyi P. (1993) The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron, 11 (4): 771-87. [PMID:8104433]

6. Bennett CE, Burnett DA, Greenlee WJ, Knutson CE, Korakas P, Li C, Tulshian D, Wu WL, Bertorelli R, Fredduzzi S et al.. (2012) Fused tricyclic mGluR1 antagonists for the treatment of neuropathic pain. Bioorg Med Chem Lett, 22 (4): 1575-8. [PMID:22266036]

7. Berthele A, Laurie DJ, Platzer S, Zieglgänsberger W, Tölle TR, Sommer B. (1998) Differential expression of rat and human type I metabotropic glutamate receptor splice variant messenger RNAs. Neuroscience, 85 (3): 733-49. [PMID:9639268]

8. Bhave G, Karim F, Carlton SM, Gereau 4th RW. (2001) Peripheral group I metabotropic glutamate receptors modulate nociception in mice. Nat Neurosci, 4 (4): 417-23. [PMID:11276233]

9. Brody SA, Conquet F, Geyer MA. (2003) Disruption of prepulse inhibition in mice lacking mGluR1. Eur J Neurosci, 18 (12): 3361-6. [PMID:14686909]

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