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FLASH GENE

Symbol

GRIK2

contributors: mlm/pgu - updated : 11-04-2019

HGNC name	glutamate receptor, ionotropic, kainate 2
HGNC id	4580

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MRT6 mental retardation autosomal recessive 6
Location	6q16.3      Physical location : 101.846.860 - 102.517.957
Synonym name	excitatory amino-acid receptor 4
	glutamate receptor 6
	glutamate receptor form A
Synonym symbol(s)	GLUR6, EAA4, GLR6, GLK2, MGC74427, bA487F5.1, GLUK6, GLUK6, GluK2, MRT6

DNA

TYPE	functioning gene
STRUCTURE	671.05 kb     17 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

Promoter

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	different splice variants involving the C-terminal domain (Barbon 2008) five variants differnetially expressed, GLUR6A is brain-specific whereas GLUR6B, GLUR6C, GLUR6D, GLUR6E are expressed in fibroblast cell lines (specific for non-neuronal cells) (PMID: 20230879)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_021956 16 splicing 4592 NP_068775 102.6 908 . highly present on the surface of the plasma membrane 2008 18289788 isoform 1, GLUR6A NM_175768 17 splicing 4679 NP_786944 98 869 . poorly transported to the membrane 2008 18289788 isoform 2, GLUR6B NM_001166247 - splicing 4724 NP_001159719 - 892 . poorly transported to the membrane . mainly expressed in non-neuronal cells and barely expressed in neuronal ones 2010 20230879 isoform 3, GLUR6C can generate functional receptors with characteristics similar to the GLUR6B variant might have unique properties in non-nervous cells and in the first stages of CNS development

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 Hearing/Equilibrium ear inner cochlea     Nervous brain diencephalon hypothalamus       brain hindbrain cerebellum       ganglia sensory ganglia dorsal root       nerve         Visual eye

tissue

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

cell lineage
cell lines	fibroblast cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	RPE, choroid, eye

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four transmembrane segments (4TM)
	C-terminal domain may contain residue(s) involved in the PKA-mediated potentiation, and protein-protein interactions at the C-terminal domain are important for regulating kainate receptor physiology

mono polymer

homomer , heteromer , tetramer

HOMOLOGY

interspecies	homolog to murine Grik2 (98.4pc)
	homolog to rattus Grik2 (98.8pc)

Homologene

FAMILY	glutamate-gated ion channel (TC 1.A.10) family
	GRIK2 subfamily

CATEGORY

receptor membrane , transport channel

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	may be involved in the transmission of light information from the retina to the hypothalamus
	might be involved in the maturation of microcircuits and network formation in brain areas that are important for higher brain functions, such as the hippocampus
	mediating facilitatory effects of kainate on mossy fiber synaptic transmission, important modulator of mossy fiber synaptic strength
	modulating cell surface expression of NETO2

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

neurotransmission

a component

four subunits fonctioning as ligand-activated ion channels

INTERACTION

DNA

RNA

small molecule

protein	interacting with GRIK1 AND KIF17
	interacting with DLG4 and NETO2
	KLHL17 is able to bind to GRIK2, a kainate-type glutamate receptor subunit, and target GRIK2 for degradation
	GRIK1, GRIK2, interact with the spectrin-actin binding scaffolding protein EPB41L1 through a membrane-proximal domain in the C-terminal tail
	regulation of GRIK2 by SGK1 and NDRG2 in astrocytes may play an important role in gliotransmission, modulation of gene expression and regulation of exocytosis of tissue-type plasminogen activator (tPA)
	TTBK2 down-regulates GRIK2 activity by decreasing the receptor protein abundance in the cell membrane via RAB5A-dependent endocytosis, an effect that may protect against neuroexcitotoxicity

cell & other

REGULATION

Other	phosphorylation by PKC regulates endocytosis of GRIK2 at the plasma membrane
	sumoylated by PIAS3 and desumoylated by SENP1
	subject to RNA editing at multiple sites, which is thought to alter the structure and fonction of the receptor complex

ASSOCIATED DISORDERS

corresponding disease(s)

MRT6

Susceptibility

may be associated with susceptibility for obsessive-compulsive disorder to chronic fatigue syndrome (CFS)

Variant & Polymorphism SNP	G allele of rs2247215 (GRIK2) were more likely to have CFS and CFS subjects showed decreased GRIK2 expression

Candidate gene	for AUTS18
	may be involved in the excitotoxicity in the pathogenesis of Huntington disease
Marker
Therapy target

ANIMAL & CELL MODELS