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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
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