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FLASH GENE

Symbol

GRM1

contributors: mct - updated : 17-10-2017

HGNC name	glutamate receptor, metabotropic 1
HGNC id	4593

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	SCA44 spinocerebellar ataxia 44 SCAR13 spinocerebellar ataxia, autosomal recessive 13
Location	6q24.3      Physical location : 146.348.781 - 146.758.731
Synonym name	protein phosphatase 1, regulatory subunit 85
Synonym symbol(s)	MGLUR1, GPRC1A, GRM1A, MGLU1, MGLUR1A, GPRC1A, PPP1R85, SCA44, SCAR13

DNA

TYPE	functioning gene
STRUCTURE	409.96 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site
text structure	canonical binding site for FMR1 at the 3'UTR

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - EPM2A EPM2A - D6S1703 - D6S1342 - D6S1042 - [D6S1649 - D6S148 - D6S978 ] - qter
Text	[GRM1 ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed mGlu1h receptor - - - - - mRNA was observed in two different melanoma cell lines and is overexpressed, compared with melanoma precursor cells, melanocytes 2013 23481697 encodes a predicted C-terminal splice variant of 10 additional amino acids play a distinct role in primate glutamatergic signaling NM_001278066 9 - 6757 NP_001264995 - 906 - 2014 25158311 NM_001278065 10 - 6839 NP_001264994 - 906 . GRM1A and GRM1B variants distribution overlaps in Purkinje cells and the two variants colocalize in their spines . GRM1A, GRM1B show distinct sub-cellular localization when expressed alone in neurons 2014 25158311 GRM1B NM_001278064 8 - 6707 NP_001264993 - 1194 . GRM1A and GRM1B variants distribution overlaps in Purkinje cells and the two variants colocalize in their spines . GRM1A, GRM1B show distinct sub-cellular localization when expressed alone in neurons 2014 25158311 GRM1A a long C-terminal domain (341 amino acids), shown to scaffold with several proteins and contribute to the structure of the post-synaptic density predominant splice variant in Purkinje cells, having a long (C)-terminal domain that interacts with HOMER scaffolding proteins NM_001278067 8 - 6672 NP_001264996 - 908 - 2014 25158311

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       highly Homo sapiens   brain forebrain cerebral cortex     Homo sapiens   brain hindbrain cerebellum   highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Nervous Purkinje cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	seven transmembrane segments (7TM) receptor
	C-terminal PDZ-binding motif

HOMOLOGY

Homologene

FAMILY

G-protein coupled receptor family

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,nucleus
text	recruitment to lipid rafts is enhanced by agonist binding and is supported at least in part by an intact cholesterol recognition/interaction amino acid consensus (CRAC) motif in the receptor

basic FUNCTION	activating PI turnover and triggering intracellular calcium release
	important neuronal mediator of postsynaptic signaling that influence synaptic strength, plasticity, and other factors
	control metaplasticity of spinal learning through a PKC-dependent mechanism
	with GRM5, plays a role in the early stages of corticogenesis with, however, a different contribution to human cortical developmental events
	involved in synaptic activities, learning and neuroprotection
	important role of GRM1 in pain-related amygdala plasticity and evidence for the involvement of HOMER1 proteins in the forebrain in the modulation of pain hypersensitivity
	plays an important role in cerebellar development and synaptic plasticity
	can be an oncogene in epithelial cells
	GRM1, GRM5 play critical functions in forms of activity-dependent synaptic plasticity and synapse remodeling in physiological and pathological states
	assembly of two covalently linked monomers into dimeric complexes is a prerequisite for metabotropic glutamate receptor 1 (GRM1) function
	plays an important role in synaptic plasticity and cerebellar development
	GRM1, GRM5 are key elements in the dynamic regulation of cholinergic synaptic inputs onto neurons of the thalamic reticular nucleus (TRN)
	novel function of ubiquitination in the regulation of GRM1, as well as its role in mGluR-dependent AMPAR endocytosis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

constituent of phosphate receptors

INTERACTION

DNA

RNA

small molecule

protein	binding to homer proteins
	activating FMR1, TRPC1 and DLG4(activation GRM1-dependent)
	binding partner of GOPC, through its PSD95/discslarge/ZO1 homology domain (inhibit GRM1-mediated ERK1/2 activation, without an apparent effect, via the C-terminal-truncated receptor)
	molecular link between GRM1 and FMR1 in the anterior cingulate cortex (ACC), a key region involved in high brain cognitive and executive functions
	associates with the PDZ protein tamalin (GRASP)
	interaction with caveolin-1 which controls the rate of constitutive GRM1 internalization
	in addition to the MAPK pathway previously reported being a downstream target of stimulated GRM1, AKT2 is another downstream target in GRM1 mediated melanocyte transformation
	STIM1 controls neuronal Ca++ signaling, GRM1-dependent synaptic transmission, and cerebellar motor behavior
	cooperative signaling between GRM1 and GRM5 is in a manner inconsistent with heterodimerization, and thus suggest an interaction between homodimers
	NRG1 selectively increases GRM1-activated currents by inducing synthesis and trafficking to membrane of functional receptors
	NCDN interacts with GRM1 and GRM5

cell & other

linked to inositol phosphate receptors

REGULATION

Other

regulation of its localization and function by Homer proteins

ASSOCIATED DISORDERS

corresponding disease(s)

SCAR13 , SCA44

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   aberrantly expressed in melanomas tumoral       gain of function through gene fusion and promoter swapping in chondromyxoid fibroma

Susceptibility

to melanoma

Variant & Polymorphism other	increasing the risk of GRM1

Candidate gene
Marker
Therapy target	potential therapeutic target for promoting use-dependent plasticity after spinal cord injury

ANIMAL & CELL MODELS