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FLASH GENE
Symbol SLC18A2 contributors: mct - updated : 11-04-2020
HGNC name solute carrier family 18 (vesicular monoamine), member 2
HGNC id 10935
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • twelve transmembrane spanning segments (12TM)
  • HOMOLOGY
    interspecies homolog to murine Slc18a2
    Homologene
    FAMILY
  • major facilitator superfamily
  • vesicular transporter family
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text vesicular membrane
    basic FUNCTION
  • involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters
  • essential for loading monoamines into vesicles and maintaining normal neurotransmission
  • regulates neurotransmission and reduces cytosolic toxicity of monoamines
  • during the stimulus, the endocytosis of VMAT2 (but not VGLUT1) accelerates dramatically in midbrain dopamine but not hippocampal neurons, indicating a novel, cell-specific mechanism to sustain high rates of release
  • sequesters cytoplasmic dopamine into synaptic vesicles for storage and release
  • catalyzes transport of monoamines into storage vesicles in a process that involves exchange of the charged monoamine with two protons
  • is responsible for sequestering cytosolically toxic dopamine into intracellular secretory vesicles
  • by regulating the storage of monoamines transmitters into synaptic vesicles, has a protective role against their cytoplasmic toxicity
  • causal link between reduced SLC18A2 expression and fear behavior, consistent with the correlational relationship between SLC18A2 genotype and post-traumatic stress disorder (PTSD) risk
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • direct binding between the N-terminus and the third cytoplasmic loop of SLC18A2, as well as, a region containing the substrate binding and the C-terminal domains of HSPA8
  • PARK7 stimulates SLC18A2 activity in the synapse by transactivation of the SLC18A2 gene and by direct binding to SLC18A2 and cysteine 106 is necessary for the stimulating activity of PARK7 toward SLC18A2
  • cell & other
    REGULATION
    inhibited by fluoxetine (inhibited the activity of SLC18A2 by a mechanism different from that of reserpine and did not directly interact with the active site of SLC18A2
    Other regulated by HSPA8 (important role for HSPA8 in SLC18A2 function and regulation)
    ASSOCIATED DISORDERS
    corresponding disease(s) PKDYS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in platelets from patients with Parkinson disease
    constitutional     --over  
    might be a compensatory mechanism to restore and maintain synaptic transmission in dopaminergic midbrain neurons during nicotine withdrawal
    tumoral     --low  
    silencing by DNA hypermethylation and/or allelic loss is a frequent event in prostate cancer and a novel independent predictor of biochemical recurrence after prostatectomy
    constitutional germinal mutation      
    in microphthalmia
    Susceptibility
  • to alcoholism
  • to Parkinson disease
  • to schizophrenia and bipolar disorder
  • to heroin dependence
  • to sporadic amyotrophic lateral sclerosis (SALS)
  • Variant & Polymorphism SNP
  • 14234G>A and 2504T>C decreasing the risk of alcoholism
  • protective role for gain-of -function haplotypes in sporadic Parkinson disease, through increasing of sequestration of dopamine in secretory vesicles
  • GG of rs363371 in SLC18A2 may reduce the risk for sporadic amyotrophic lateral sclerosis (SALS)
  • SLC18A2 SNPs (rs363332, rs363334 and rs363338) associated with heroin dependence
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    target of genetic medications for PD
    neurologyneurodegenerative 
    SLC18A2 may be considered a therapeutic target for the treatment and/or prevention of Tardive dyskinesia (TD)
    ANIMAL & CELL MODELS
  • Vmat2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity