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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
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