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FLASH GENE

Symbol

GRM2

contributors: mct/npt - updated : 11-02-2013

HGNC name	glutamate receptor, metabotropic 2
HGNC id	4594

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	3p21.2      Physical location : 51.741.080 - 51.752.623
Synonym name	glutamate receptor homolog
Synonym symbol(s)	GLUR, MGLUR2, GPRC1B, mGlu2

DNA

TYPE	functioning gene
STRUCTURE	11.55 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	pter - D3S3582 - COL7A1 - MST1R - UBE1L - GRM2 - D3S1578 - D3S1588 - cen
Authors	GeneMap (98)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000839 6 - 3389 NP_000830 95.6 872 - Gonzalez-Maeso (2008) NM_001130063 4 - 1985 NP_001123535 - 254 - -

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain limbic system       Homo sapiens Adult nervous brain basal nuclei putamen     Nervous brain basal nuclei globus pallidus     Respiratory respiratory tract trachea       Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text

brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

seven transmembrane segments (7TM) receptor

conjugated

GlycoP

mono polymer

heteromer

HOMOLOGY

Homologene

FAMILY	G protein coupled receptor superfamily
	G-protein coupled receptor 3 family

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm

basic FUNCTION	metabotropic glutamate receptor, goup II, linked to the inhibition of cAMP cascade
	involved in glutamate homeostasis as well as in glial proliferation
	may participate in mediating the survival of neurons in the face of selective neuronal dysfunction and degeneration in Alzheimer disease
	is resistant to agonist-induced homologous desensitization
	functional plasticity of GRM2 in regulating spinal excitatory and inhibitory synaptic input in neuropathic pain
	GRM2, and GRM3, are inhibitory autoreceptors that negatively modulate the adenylate cyclase signaling cascade
	within the hippocampus, GRM2 is believed to play a key role in the induction of long-term depression (LTD) at mossy fiber-CA3 synapses
	plays an important role on the presynaptic control of glutamate release, and negative allosteric modulators (NAMs) acting on GRM2/GRM3 are under assessment for their potential as antidepressants, neurogenics and cognitive enhancers
	GRM2 and HTR2A form a functional heteromeric complex through which hallucinogenic drugs cross-signal to the Gi-coupled receptor
	monomeric, couples to G proteins upon direct activation by a positive allosteric modulator
	dimeric GRM2 activates G protein upon glutamate binding, suggesting that dimerization is required for glutamate induced activation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	complexing with HTR2A (complex that may be involved in the altered cortical processes of schizophrenia)
	HTR2A/GRM2 complex is necessary for the neuropsychological responses induced by hallucinogens 8)

INTERACTION

DNA

RNA

small molecule

protein

heteromeric complex between the HTR2A and GRM2, integrates ligand input, modulating signaling output and behavioral changes

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in amyotrophic lateral sclerosis spinal cord constitutional     --low   in brain from untreated schizophrenic subjects constitutional     --over   in pyramidal neurons in the hippocampus of Alzheimer disease and often co-localizes with neurofibrillary pathology constitutional     --over   in schizophrenia, significantly higher levels of GRM2 mRNA in the prefrontal white matter

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed psychiatry bipolar disorder   GRM2/GRM3 antagonists are promising targets for the discovery of novel antidepressants psychiatry schizophrenia   complex HTR2A/GRM2 is a promising new target for the treatment of psychosis

ANIMAL & CELL MODELS