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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
Corresponding disease
EIEE41 epileptic encephalopathy, early infantile, 41
Location 11p13      Physical location : 35.272.752 - 35.441.105
Synonym name
  • excitatory aminoacid transporter 2
  • glutamate transporter 1
  • glial high affinity glutamate transporter
  • glutamate/aspartate transporter II
  • sodium-dependent glutamate/aspartate transporter 2
  • glutamate/aspartate transporter II
  • Synonym symbol(s) EAAT2, GLT1, EAA2, GLT-1, HBGT
    DNA
    TYPE functioning gene
    STRUCTURE 168.86 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure promoter highly expressed in astrocytes, may be useful for targeting gene expression in the brain and for identifying molecules capable of modulating glutamate transport
    MAPPING cloned Y linked N status confirmed
    Physical map
    GA17 11p13 hypothetical protein BC009561 RPL34P2 11p13 ribosomal protein L34 pseudogene 2 TMG4 11p13 transmembrane gamma-carboxyglutamic acid protein 4 FLJ21924 11p13 hypothetical protein FLJ21924 LOC91614 11p13 novel 58.3 KDA protein FLJ11336 11p13 hypothetical protein FLJ11336 PIGCP1 11p13-p12 phosphatidylinositol glycan, class C, pseudogene 1 CSTF3 11p13 cleavage stimulation factor, 3' pre-RNA, subunit 3, 77kDa LOC390107 11 similar to ribosomal protein S24 HIPK3 11p13 homeodomain interacting protein kinase 3 G2 11p13 G2 protein MGC34830 11p13 hypothetical protein MGC34830 CD59 11p13 CD59 antigen p18-20 (antigen identified by monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344) FBXO3 11p12 F-box only protein 3 LOC390108 11 similar to hypothetical protein MGC40611 LMO2 11p13 LIM domain only 2 (rhombotin-like 1) M11S1 11p13 membrane component, chromosome 11, surface marker 1 FLJ10774 11p13 N-acetyltransferase-like protein ABTB2 11p13 ankyrin repeat and BTB (POZ) domain containing 2 CAT 11p13 catalase ELF5 11p15-p13 E74-like factor 5 (ets domain transcription factor) EHF 11p12 ets homologous factor MMRP19 11p13 likely ortholog of mouse monocyte macrophage 19 PDHX 11p13 pyruvate dehydrogenase complex, component X CD44 11p13 CD44 antigen (homing function and Indian blood group system) SLC1A2 11p13-p12 solute carrier family 1 (glial high affinity glutamate transporter), member 2 DKFZP586H2123 11p13 DKFZP586H2123 protein FJX1 11p13 four jointed box 1 (Drosophila) TRIM44 11p12-14 tripartite motif-containing 44 LOC119722 11p13 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC143458 11p13 hypothetical protein LOC143458 HSPC166 11p13 HSPC166 protein FLJ14213 11p13 hypothetical protein FLJ14213 TRAF6 11p13-p12 TNF receptor-associated factor 6 RAG1 11p13 recombination activating gene 1 RAG2 11p13 recombination activating gene 2 LOC119710 11p13 hypothetical protein BC009561
    RNA
    TRANSCRIPTS type messenger
    text five transcripts alternatively spliced from 5'utr, untranslated exons (PMID: 11038258 ) and four from different cleavage and polyadenylation sites
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 12021 - 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
  • - 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)
  • 12 - 11581 - 565 - 2010 20688910
    - splicing - - - in brain tissues 2010 20688910
  • seem to alter glutamate transport capability
  • - splicing - - - . expressed both intracellularly and at the cell surface . in brain tissues 2010 20688910
  • seem to alter glutamate transport capability
  • 12 - 11724 - 565 - 2010 20688910
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly Mus musculus
    Nervousbraindiencephalonhypothalamus highly
     brainforebraincerebral cortex highly
     brainhindbraincerebellum highly
     braindiencephalonthalamus highly
    Respiratoryrespiratory tractlarynx  highly
     respiratory tracttrachea  highly
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    Nervouscentralwhite matter   Homo sapiensFetal
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte
    Nervousglia
    Nervousneuron Homo sapiensFetal
    Visualcone 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    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
    neurologyneurodegenerative 
    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