Gene Report

Basic Information

Approved Symbol	GRM1
Approved Name	glutamate receptor, metabotropic 1
Symbol Alias	GPRC1A, mGlu1, MGLUR1
Location	6q24
Position	chr6:146348782-146758731 (+)
External Links	Entrez Gene: 2911 Ensembl: ENSG00000152822 UCSC: uc010khw.1 HGNC ID: 4593
No. of Studies (Positive/Negative)	2(2/0)
Type	Literature-origin; SNP mapped

Positive relationships between GRM1 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
GRM1	Menke A, 2012	patients and normal controls	allelic P-value=7.0E(-5)	Within the GRM1 locus, 22 SNPs showed nominally significant ...... Within the GRM1 locus, 22 SNPs showed nominally significant association with UPD, of which 6 withstood corrections for multiple testing (rs2268666 with best allelic p=7.0x10(-5)). More...

Positive relationships between GRM1 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
Grm1		SLC17A7(vesicular glutamate transporter 1 (VGLUT1))	gene	Tordera RM, 2011	animal model		gene was regulated in frontal cortex of VGLUT1(+/-) mice gene was regulated in frontal cortex of VGLUT1(+/-) mice

Positive relationship network of GRM1 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between GRM1 and MDD (count: 0)

Negative relationships between GRM1 and other components at different levels (count: 0)

GRM1 related SNPs in MK4MDD (count: 1)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs2268666	chr6:146746088(Forward)	intron_variant	1(1/0)

GRM1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Metabotropic glutamate receptor 1	Q13255	0(0/0)	Gene mapped

GRM1 related GO terms (count: 15)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0007268	synaptic transmission	biological process	TAS[9076744]

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0004930	G-protein coupled receptor activity	molecular function	TAS[7476890]
GO:0071257	cellular response to electrical stimulus	biological process	IEA
GO:0005634	nucleus	cellular component	IEA
GO:0005887	integral to plasma membrane	cellular component	TAS[7476890]
GO:0008066	glutamate receptor activity	molecular function	TAS[7476890]
GO:0051930	regulation of sensory perception of pain	biological process	IEA
GO:0014069	postsynaptic density	cellular component	IEA
GO:0007626	locomotory behavior	biological process	IEA
GO:0019233	sensory perception of pain	biological process	IEA
GO:0008219	cell death	biological process	IEA
GO:0007186	G-protein coupled receptor signaling pathway	biological process	TAS[7476890]
GO:0005886	plasma membrane	cellular component	TAS
GO:0000187	activation of MAPK activity	biological process	IEA
GO:0000186	activation of MAPKK activity	biological process	IEA

GRM1 related KEGG pathways (count: 5)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04020	calcium signaling_pathway	Calcium signaling pathway	Ca2+ that enters the cell from the outside is a principal so...... Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM). More...
hsa04730	long term_depression	Long-term depression	Cerebellar long-term depression (LTD), thought to be a molec...... Cerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and Purkinje cells (PCs) induced by the conjunctive activation of PFs and climbing fiber (CF). Multiple signal transduction pathways have been shown to be involved in this process. Activation of PFs terminating on spines in dendritic branchlets leads to glutamate release and activation of both AMPA and mGluRs. Activation of CFs, which make multiple synaptic contacts on proximal dendrites, also via AMPA receptors, opens voltage-gated calcium channels (VGCCs) and causes a generalized influx of calcium. These cellular signals, generated from two different synaptic origins, trigger a cascade of events culminating in a phosphorylation-dependent, long-term reduction in AMPA receptor sensitivity at the PF-PC synapse. This may take place either through receptor internalization and/or through receptor desensitization. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04080	neuroactive ligand_receptor_interaction	Neuroactive ligand-receptor interaction
hsa04720	long term_potentiation	Long-term potentiation	Hippocampal long-term potentiation (LTP), a long-lasting inc...... Hippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippocampus induces glutamate release and activation of glutamate receptors in dendritic spines. A large increase in i resulting from influx through NMDA receptors leads to constitutive activation of CaM kinase II (CaM KII). Constitutively active CaM kinase II phosphorylates AMPA receptors, resulting in potentiation of the ionic conductance of AMPA receptors. Early-phase LTP (E-LTP) expression is due, in part, to this phosphorylation of the AMPA receptor. It is hypothesized that postsynaptic Ca2+ increases generated through NMDA receptors activate several signal transduction pathways including the Erk/MAP kinase and cAMP regulatory pathways. The convergence of these pathways at the level of the CREB/CRE transcriptional pathway may increase expression of a family of genes required for late-phase LTP (L-LTP). More...
hsa04540	gap junction	Gap junction	Gap junctions contain intercellular channels that allow dire...... Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation. More...

GRM1 related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
CK1_PATHWAY	ck1 pathway	Regulation of ck1/cdk5 by type 1 glutamate receptors	Cdk5 is a cyclin dependent protein kinase involved in dopami...... Cdk5 is a cyclin dependent protein kinase involved in dopaminergic signaling in the neostriatal region of the brain. The role of cdk5 in dopamine responses occurs through phosphorylation of DARPP-32. Caseine kinase 1 (CK1) also regulates DARPP-32 phosphorylation and dopamine signaling. The phosphorylation of DARPP-32 by cdk5 reduced dopamine signaling. Depending on its phosphorylation state, DARPP-32 inhibits either protein phosphatase 1 (PP1) or PKA. The role of mGLUR1 in this process is supported by the induction of cdk5 and CK1 activity by the mGLUR1 agonist DHPG and the subsequent phosphorylation of DARPP-32 associated with DHPG treatment of nigrostriatal neurons. CK-1 and Ckd5 inhibitors block the DHPG induced DARPP-32 phosphorylation. Dopamine exerts a positive signal that increases dopamine response by reversing phosphorylation of DARPP-32 at threonine-75. Dopamine initiates this pathway through activation of the D1 dopamine receptor, a Gs coupled GPCR, elevating cAMP and activating PKA. PKA activates protein phosphatase 2A (PP2A) which dephosphorylates DARPP-32 and increases dopamine responsiveness. This also removes the inhibition of PKA by DARPP-32, forming a positive feedback loop for further DARPP-32 inactivation by PKA. Activation of the D2 dopamine receptor has the opposite effect, shifting the DARPP-32 population toward the threonine-75 phosphorylated form. More...

GRM1 related Reactome pathways (count: 2)

ID	Name	Description
Gene mapped Reactome pathways
REACT_21340	gpcr ligand_binding	There are more than 800 G-protein coupled receptor. GPCRs ar...... There are more than 800 G-protein coupled receptor. GPCRs are receptors for a diverse range of ligands from large proteins to photons and have an equal diverstiy of ligand-binding mechanisms. Classical GPCR signaling involves signal transduction via heterotrimeric G-proteins, however many G-protein independent mechanisms have been reported. More...
REACT_18319	class c3_metabotropic_glutamate_pheromone_receptors	The class C G-protein-coupled receptors are a class of G-pro...... The class C G-protein-coupled receptors are a class of G-protein coupled receptors that include the metabotropic glutamate receptors and several additional receptors. Family C GPCRs have a large extracellular N-terminus which binds the orthosteric (endogenous) ligand. The shape of this domain is often likened to a clam. Several allosteric ligands to these receptors have been identified and these bind within the seven transmembrane region. More...

GRM1 related interactors from protein-protein interaction data in HPRD (count: 12)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
GRM1	HOMER2	No	in vitro	9808458
GRM1	TUBB	No	in vitro	9886087
GRM1	GAPDH	No	in vitro	9886087
GRM1	GPRASP1	No	in vitro	15452121
GRM1	ADRBK1	No	in vitro;in vivo	15870073
GRM1	GRM1	Yes	in vitro;in vivo	11850456 , 10349865 , 10945991
GRM1	GRASP	No	in vivo;yeast 2-hybrid	11850456
GRM1	HOMER1	No	in vitro	9069287
GRM1	ITPR1	Yes	in vivo	9808459
GRM1	ADORA1	No	in vitro	11278325
GRM1	PRKCA	No	in vitro	10823959
GRM1	EFNB2	No	in vivo	15745950

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways