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FLASH GENE

Symbol

SLC1A2

contributors: mct - updated : 13-09-2016

HGNC name	solute carrier family 1 (glial high affinity glutamate transporter), member 2
HGNC id	10940

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	five transcripts alternatively spliced from 5'utr, untranslated exons (PMID: 11038258 ) and four from different cleavage and polyadenylation sites

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004171 11 - 12021 NP_004162 - 574 . expressed both intracellularly and at the cell surface . in brain tissues . higher mRNA transcript expression in Alzheimer-diseased brain with increasing pathological severity 2010 20688910 can form heteromeric complexes with variants EAAT2b, EAAT2delta7, and EAAT2delta9 that alter glutamate-induced fluorescence and current changes of the complex EAAT2b - splicing - - - . only expressed in brain astrocytic processes, not in neurons, although some neuronal expression occurs in retina . expressed both intracellularly and at the cell surface . higher mRNA transcript expression in Alzheimer-diseased brain with increasing pathological severity 2010 20688910 C-terminal variant cytoplasmic C terminus contains a postsynaptic density-95/Discs large/zona occludens-1 (PDZ) ligand surface expression and function of EAAT2b can be rapidly modulated through the disruption of its interaction with DLG1 by CAMK2A activation (PMID: 25834051) NM_001195728 12 - 11581 NP_001182657 - 565 - 2010 20688910 EAAT2delta7 - splicing - - - in brain tissues 2010 20688910 seem to alter glutamate transport capability EAAT2delta9 - splicing - - - . expressed both intracellularly and at the cell surface . in brain tissues 2010 20688910 seem to alter glutamate transport capability NM_001252652 12 - 11724 NP_001239581 - 565 - 2010 20688910

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 Endocrine pancreas       highly Mus musculus Nervous brain diencephalon hypothalamus   highly   brain forebrain cerebral cortex   highly   brain hindbrain cerebellum   highly   brain diencephalon thalamus   highly Respiratory respiratory tract larynx     highly   respiratory tract trachea     highly Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly Nervous central white matter     Homo sapiens Fetal

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Nervous glia Nervous neuron Homo sapiens Fetal Visual cone photoreceptor

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	ten transmembrane spanning segments (10TM)
	six N terminal and cytoplasmic N and C termini

mono polymer

homomer , trimer

HOMOLOGY

interspecies

homolog to murine Eaat2

Homologene

FAMILY

sodium : dicarboxylate (SDF) symporter family

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm
text	sumoylated SLC1A2 localizes to intracellular compartments, whereas non-sumoylated SLC1A2 resides on the plasma membrane

basic FUNCTION	glial high affinity glutamate transporter, Na and K dependent, modulating synaptic glutamate, and predominant glutamate transporter on blood platelets
	transporter that actively removes the excitatory neurotransmitter glutamate from the extracellular space
	playing a necessary role for brain development through regulation of extracellular glutamate concentration
	play a key role in the regulation of extracellular glutamate levels in the brain by removing glutamate from the extracellular fluid
	is one of the major glutamate transporters expressed in astroglia and is responsible for clearing glutamate from the extracellular space at the synapse
	responsible for most of the glutamate transport in the adult brain
	principal mediator of glutamate clearance to terminate glutamate-mediated responses
	acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies
	ADORA1 as well as SLC1A2 might regulate ethanol intake
	as with liver and brain, one possible role of SLC1A2 in the pancreas is to support glutamine synthesis
	predominantly astroglial glutamate transporter responsible for the majority of synaptic glutamate clearance in the mammalian central nervous system (CNS)
	play likely a secondary yet significant role in the Glutamate reuptake activity at the rod and the cone output synapses

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

active transport

PATHWAY

metabolism

signaling

neurotransmission

a component

INTERACTION

DNA

RNA

small molecule

protein	LIM protein JUB, allowing SLC1A2 to regulate intracelllular signaling or interaction with cytoskeleton inhibited by N-(4-acetyl-1-piperazinyl)-p-fluorobenzoamide monohydrate FK960
	interacting with ADORA1 (regulates SLC1A2 expression in astrocytes)
	PICK1 may not only affect glutamatergic neurotransmission by its regulatory effect on glutamate receptors but may also affect neuronal excitability via an increased SLC2A1-mediated leak current
	CAV1 is a powerful negative regulator of the excitatory glutamate transporters SLC1A1, SLC1A2, SLC1A3, SLC1A6

cell & other

REGULATION

activated by

KL that up-regulates the excitatory glutamate transporters SLC1A3 and SLC1A2 and thus participates in the regulation of neuronal excitation

Other

regulated by GRM3

ASSOCIATED DISORDERS

corresponding disease(s)

EIEE41

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in amyotrophic lateral sclerosis, motor cortex and spinal cord constitutional     --low   may be an adaptive response to neuronal death or it may be a causative event contributing to neuronal death constitutional       loss of function implicated in acute and chronic neurological disorders, including stroke/ischemia, temporal lobe epilepsy, amyotrophic lateral sclerosis, Alzheimer disease, human immunodeficiency virus 1-associated dementia, and growth of malignant gliomas

Susceptibility

to idiopathic epilepsy (generalized or absence) to autism spectrum disorder to epileptic encephalopathies (EEs) to Parkinson disease (PD)

Variant & Polymorphism other	a variant acting as a putative modifier for the spastic paraplegia phenotype
	SLC1A2 rs3794087 may decrease the risk for PD
	recurrence of the SLC1A2 p.Gly82Arg variant might be accounted for by a homopolymer stretch of guanines in epileptic encephalopathies (EEs)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous pain   enhanced glutamate uptake provides protective effects against colonic distension-induced nociception and represents an exciting new mechanistic approach leading to better therapeutic options to visceral pain disorders neurology neurodegenerative   mechanism for ceftriaxone modulation of glutamate transport and for its potential effects on ameliorating specific neurodegenerative diseases through modulation of extracellular glutamate

ANIMAL & CELL MODELS

Slc1a2 null mice exhibit lethal spontaneous epileptic seizures, and very few animals survive beyond 13 weeks