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FLASH GENE
Symbol SLC6A5 contributors: mct - updated : 03-11-2015
HGNC name solute carrier family 6 (neurotransmitter transporter, glycine), member 5
HGNC id 11051
Corresponding disease
STHE3 Startle disease, hyperekplexia 3
Location 11p15.1      Physical location : 20.620.945 - 20.676.608
Synonym name
  • presynaptic glycine transporter 2
  • glycine transporter 2
    • Synonym symbol(s) GLYT2, NET1, GLYT-2, HKPX3
    DNA
    TYPE functioning gene
    STRUCTURE 55.67 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 2863 - 797 - 2001 11709067
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainhindbrainmedulla oblongata  
     brainhindbraincerebellum  
     spinal cord    
    Visualeyeretina  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Rattus norvegicus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • twelve transmembrane segments
  • at its extreme C-terminus, carries a type III PDZ domain binding motif (PDZ-ligand motif), which interacts with the PDZ domain protein syntenin-1
    • HOMOLOGY
    Homologene
    FAMILY
  • sodium: neurotransmitter symporter (SNF) family
    • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • being localized mainly on large, dense-core vesicles
  • intracellular SLC6A5 resides in a subset of endosomal membranes and may traffic around several compartments, mainly RAB11-positive endosomes
  • constitutively internalized from cell surface lipid rafts, remaining associated with rafts in subcellular recycling structures
  • astrocytes express functional SLC6A5, which challenge previous findings that those cells would express only SLC6A9, whereas SLC6A5 was supposed to be restricted to the glycinergic nerve terminals
  • is exclusively found at presynaptic glycinergic terminals
    • basic FUNCTION
  • involved in the termination of neurotransmission at strychnine sensitive glycinergic synapses
  • likely mediating glycine uptake in cortical fiber cells
  • being responsible for the accumulation of glycine in the center of the lens
  • Na+/Cl&
    • 8722;-dependent neurotransmitter transporter that maintains a high presynaptic pool of glycine at glycinergic synapses
  • rapidly trafficked first towards the plasma membrane and then internalized under conditions that stimulate vesicular glycine release
  • plays an important role in transporter trafficking to and/or stabilization at synaptic sites through its C-terminal PDZ-ligand motif
  • controls the availability of the neurotransmitter in glycinergic synapses, and the modulation of its function may influence synaptic transmission
  • constitutively recycles between the cell interior and the plasma membrane by means of a monensin-sensitive trafficking pathway
  • implicated in the SLC6A5 trafficking regulation in the central nervous system
  • mediates the forskolin-induced increase of glycinergic transmission
  • glycine transport by SLC6A9 is inhibited by lithium whereas SLC6A5 transport is stimulated, and this effect is more evident at increased glycine concentrations
  • contributions of SLC6A5 and SLC6A9 to the regulation of extracellular glycine concentrations at glycinergic synapses changes likely during development
  • neuronal glycine transporter that mediates the reuptake of the neurotransmitter that is used to refill synaptic vesicles in the terminal
  • SLC6A5, SLC6A9 are the transporters responsible for glycine uptake from the synaptic cleft
  • involved in the removal and recycling of synaptic glycine from inhibitory synapses
  • presynaptic control of SLC6A5 by physical and functional association with plasma membrane Ca2+-ATPase SLC8A1 and ATP2B1
  • SLC6A5, SLC6A9 are responsible for the termination of glycine-mediated synaptic activity through removal of neurotransmitter from synaptic cleft
  • is required for the replenishment of presynaptic glycine reservoirs
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • syntaxin 1 (for protein trafficking)
  • interacting with syntaxin-1 involved in the exocytosis of neurotransmitters (involved in the transport of SLC6A5 to, but not its retrieval from, the plasma membrane)
  • PRKCA negatively modulates SLC6A5 via rapid and dynamic redistribution of SLC6A5 from raft to non-raft membrane subdomains and increasing ubiquitinated SLC6A5 endocytosis
  • UCHL1, is the major regulator of neuronal ubiquitin homeostasis, and indirectly modulates the turnover of SLC6A5
  • GSK3B is important for stabilizing and/or controlling the expression of functional SLC6A5, SLC6A9 on the neural cell surface
  • BDNF, via truncated NTRK2, modulates SLC6A9 and SLC6A5 in astrocytes
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) STHE3
    Susceptibility to schizophrenia
    Variant & Polymorphism SNP SNP4 significantly associated to schizophrenia
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS