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FLASH GENE

Symbol

GRIN1

contributors: mct - updated : 21-10-2018

HGNC name	glutamate receptor, ionotropic, N-methyl D-aspartate 1
HGNC id	4584

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	alternative splicing producing isoforms differing in the C terminus

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_007327 20 splicing 4400 NP_015566 105.4 938 neurons 2000 10762714 NM_000832 19 splicing 3926 NP_000823 99.1 885 neurons 2000 10762714 also called NR1-1 missing exon 20 and alternatively spliced in exon 21 NM_021569 19 splicing 4289 NP_067544 100.9 901 neurons 2000 10762714 also called NR1-2 missing exon 20 and spliced in exon 21 sensitive to deglycosylation by endoglycosidase H variant NR1-3 21 splicing 5137 isoform NR1-3 105.4 938 neurons 2000 10762714 including all 21 exons with alternative splicing in exon 21 NM_001185091 20 splicing 3989 NP_001172020 101.5 906 neurons 2000 10762714 also called NR1-3b variant NR1-4b - splicing 3121 isoform NR1-4b 105.6 943 neurons 2000 10762714 NM_001185090 21 - 4100 NP_001172019 105.6 943 neurons 2000 10762714 also called NR1-4a sensitive to deglycosylation by endoglycosidase H

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 forebrain cerebral cortex   highly Homo sapiens   brain hindbrain cerebellum   highly   brain diencephalon hypothalamus suprachiasmatic nuclei highly Homo sapiens   brain basal nuclei         nerve cranial nerve       Visual eye retina       Rattus norvegicus

tissue

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

cells

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

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four transmembrane segments (4TM)
	a long extracellular domain
	twofold symmetry axis running through the entire molecule composed of an N terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD)
	critical role of the single AA within the GRIN1 M4 domain in the surface delivery of functional NMDA receptors

conjugated

GlycoP , PhosphoP

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to murine Grin1
	homolog to C.elegans F07f6.6

Homologene

FAMILY	ligand-gated ionic channels family
	glutamate-regulated superfamily of ion channels

CATEGORY

receptor membrane , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	post-synaptic membrane

basic FUNCTION	playing a central role in verbal memory and cognitive function
	playing a key role in the plasticity of synapses
	and in excitatory neurostransmission
	ligand-gated ion channel (Ca2+) transporting, when bound to glutamate and Mg2+ released
	playing a central role in the striatum, in long potentiation memory, motor learning and cognitive function
	playinga role in controlling T cell activation
	activates multiple kinases and changes the phosphorylation of many postsynaptic proteins organized in signaling networks
	its activation induces postnatal Müller glia-derived retinal cell progenitor proliferation and transcription factor CREB phosphorylation (activation induces postnatal Müller glia-derived retinal cell progenitor proliferation and transcription factor CREB phosphorylation)
	by tethering Galpha with mu-opioid receptor (OPM1), GRIN1 stabilizes the receptor within the lipid rafts and potentiates the receptor signaling in the neurite outgrowth processes
	main component of functional N-methyl-d-aspartic acid receptors that are involved in the glucocorticoid-induced neuronal damage
	activity of the GRIN1/GRIN2D NMDA receptor is controlled distinctively by the endogenous neurotransmitter L-glutamate
	role in controlling the intrinsic excitability of primary sensory neurons possibly via Ca(2+)-activated slow conductance K(+) (SK) channels
	primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning
	Schwann cell signaling receptor for protein ligands and a major regulator of Schwann cell physiology, which may be particularly important in peripheral nervous system (PNS) injury

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

nervous system

text	small molecule transport

PATHWAY

metabolism

signaling

neurotransmission

	glutamate signaling pathway, excitatory neurotransmission
	GRIN1/PRKCG signaling pathway may participate in the development of bone cancer pain

a component	GRIN2A, GRIN2B, GRIN2C, GRIN2D
	N-methyl D-aspartate receptor 1, zeta 1 subunit glutamate receptor
	heterodimers of an epsilon subunit and a zeta subunit
	dimer of GRIN1-GRIN2B heterodimers with the twofold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD)

INTERACTION

DNA

RNA

small molecule	metal binding,
	magnesium Mg2+ blocking the NMDA receptor in the depolarized postsynaptic membrane

protein	GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRINA
	interacting with RALA (GRIN1 activation stimulates RALA, which binds and translocates widespread RALBP1 to synapses)
	interacting with importin alpha (importin alpha is tethered at the postsynaptic density by binding to the NLS present in NR1-1a)
	NRF1 co-regulates oxidative enzymes that generate energy and neurochemicals that consume energy related to glutamatergic neurotransmission, such as KIF17, GRIN1, and GRIN2B, thereby ensuring that energy production matches energy utilization at the molecular and cellular levels
	FMR1 is required for translation downstream of GRIN1 stimulation and MOV10 is the key specificity factor in this process
	FMR1 and MOV10 have an important regulatory role in GRIN1 mediated translation at the synapse

cell & other

REGULATION

activated by

selectively activated by the artificial glutamate analog N-methyl D-aspartate

Other	regulated by C terminal phosphorylation by PKC
	activated in ischaemia

ASSOCIATED DISORDERS

corresponding disease(s)

MRD8 , DEE101

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   significantly increased in male patients with AD constitutional     --low   decreased in postmortem brain from people with schizophrenia

Susceptibility

to schizophrenia to infantile spasms responsive to to adrenocorticotropic hormone

Variant & Polymorphism other	polymorphism G1001C asssociated to allele T4197C and T5988C of GRIN2B increasing the risk of schizophrenia
	in homozygous carriers of the CTA haplotype was higher responsive to adrenocorticotropic hormone than that in heterozygous carriers and non-carriers

Candidate gene	torsion dystonia
Marker
Therapy target
	System Type Disorder Pubmed neurology acquired   a potential therapeutic target for preventing white matter damage in a variety of diseases obesity     dorsal vagal complex GRIN2A, GRIN1 can a potential therapeutic target for obesity diabete     dorsal vagal complex GRIN2A, GRIN1 can a potential therapeutic target for diabetes

ANIMAL & CELL MODELS

	CA1-specific Nmdar 1 knockout mice
	GluN1 hypomorph mice exhibit wide-ranging behavioral alterations