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FLASH GENE

Symbol

GRIA1

contributors: mct/npt/pgu - updated : 27-09-2022

HGNC name	glutamate receptor, ionotropic, AMPA 1
HGNC id	4571

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	324.25 kb     16 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - SPARC /D5S1699 - GLRA1 - D5S2077 - D5S2909 - D5S2910 - D5S119 - D5S673 - D5S1532 - D5S2910 - D5S209 - D5S410 /D5S670 - GRIA1 - D5S1431 - D5S2012 - D5S497 - D5S1698 - D5S2911 - D5S662 - D5S1507 - D5S487 - qter

RNA

TRANSCRIPTS	type	messenger

text	with flip and flop isoforms

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000827 16 - 5747 NP_000818 101.4 906 - 2021 34274350 NM_001114183 16 - 5584 NP_001107655 101.4 906 - 2021 34274350 NM_001258019 15 - 5344 NP_001244948 - 826 - 2021 34274350 NM_001258020 17 - 5641 NP_001244949 - 811 - 2021 34274350 NM_001258021 16 - 5422 NP_001244950 - 916 - 2021 34274350 NM_001258022 16 - 5422 NP_001244951 - 916 - 2021 34274350 NM_001258023 16 - 5336 NP_001244952 - 837 - 2021 34274350 NM_001364165 16 - 5416 NP_001351094 - 850 - 2021 34274350 NM_001364166 17 - 6031 NP_001351095 - 915 - 2021 34274350 NM_001364167 16 - 5946 NP_001351096 - 837 - 2021 34274350

EXPRESSION

Type

widely

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       spinal cord anterior horn     highly Homo sapiens

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage	glioblastoma cell lineage
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ligand binding site in the N terminal region
	four transmembrane segments (4TM), one of which forming the wall of the channel, and a large intracellular loop
	C-terminal domain of GRIA1 controls AMPA receptor function and trafficking during synaptic plasticity in the central nervous system

conjugated

ubiquitinated

HOMOLOGY

interspecies

homolog to murine Gria1

Homologene

FAMILY

glutamate-gated ion channel family

CATEGORY

protooncogene , signaling , receptor , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,endosome

basic FUNCTION	ligand gated ion (Cl) channel
	glutamate receptor, subunit 1, ionotropic, AMPA (amino-3-hydroxy5 methyl-isoxazole-propionic) class
	promotes dendrite growth in a non-cell-autonomous manner
	mediating the fast component of excitatory post synaptic currents in the central nervous system
	play an important role in synaptic plasticity and contribute to cell death under excitotoxic conditions
	with GRIA2, GRIA3, GRIN2B, mediate fast synaptic transmission in the brain
	spatial working memory (SWM) requires GRIA1 action in cortical circuits but is only partially dependent on GRIA1-containing AMPA receptors in hippocampus
	important roles for FXR2 and GRIA1 in neuronal development, and functional convergence between fragile X proteins in this neuronal development

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with and signaling through the protein-kinase LYN
	EPB41L1 is required for activity-dependent GRIA1 insertion, and disrupting EPB41L1-dependent GRIA1 insertion decreased surface expression of GRIA1 and the expression of long-term potentiation
	direct interaction between GRIA1, AND FRRS1L
	NMDA receptor activation regulates synaptic plasticity by causing endocytosis of AMPA receptor GRIA1
	CREB1 is necessary for the specific maintenance of the GRIA1 subunit and for its trafficking within the post-synaptic densities (PSD) during the occurrence of learning
	FMR1 and FXR2 additively promote the maturation of new neurons by regulating a common target, the AMPA receptor GRIA1, but via distinct mechanisms
	CPT1C binds GRIA1 and GRIA2 and that the three proteins have the same expression profile during neuronal maturation
	interactions of PRPF8 and GRIA1 in testis and brain cortex
	WWC1 is a novel CCDC141-binding protein that retains GRIA1 in the cytosol after internalization

cell & other

REGULATION

Other	E3 ubiquitin ligase NEDD4 responsible for GRIA1 ubiquitination, a modification that regulates multiple aspects of GRIA1 molecular biology including trafficking, localization and stability
	S-nitrosylation of GRIA1 enhances S831 phosphorylation, facilitates the associated AMPA receptor conductance increase, and results in endocytosis by increasing receptor binding to the AP2 protein of the endocytotic machinery

ASSOCIATED DISORDERS

corresponding disease(s)

IDLSE

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in cortex in FRAXA

Susceptibility

to psychotic bipolar disorder to diabetic retinopathy

Variant & Polymorphism other	variant increasing the risk of psychotic bipolar disorder
	GRIA1 (rs2195450) genes assolcitaed with diabetic retinopathy

Candidate gene	candidate gene for susceptibility to schizophrenia
Marker
Therapy target

ANIMAL & CELL MODELS

	deletion studies in mice where knockout models of the GluA1-encoding gene Gria1 have been established and report normal development and life expectancy in Gria1-/- animals (
	GluA1-knockout mice (Gria1-/-) displayed various circadian abnormalities, including misaligned, fragmented, and more variable rest-activity patterns