Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SLC6A4 contributors: mct - updated : 18-05-2016
HGNC name solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
HGNC id 11050
DNA
TYPE functioning gene
STRUCTURE 39.58 kb     15 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
Map cen - D17S841 - D17S2093 - D17S2120 - SLC6A4 - D17S1294 - D17S2103 - D17S1972 - D17S798 - qter
Text see NF1
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
15 - 4535 - 630 - 1995 7789954
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Visualeyeretina    Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
Nervouscentral   
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticplatelet
Visualganglion cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 12 transmembrane segments (12TM)
  • three Cys AAs on the second external loop, and disulfide bond formation between two AAs, Cys-200 and Cys-209, is required for SLC6A4 folding, surface expression, and transport activity
  • EL4 (Extracellular Loop 4) has an important role in controlling the conformational equilibrium of SLC6A4
  • C terminus harbors the binding site for the coat protein complex II (COPII) cargo-binding protein SEC24 , having a role in the folding of SLC6A4 and C-terminal domain recruits both the catalytic and regulatory subunits of the Ca(2+)-activated protein phosphatase calcineurin (PPP3CA)
    • secondary structure alpha-helices
    conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Slc6a4
    homolog to C.elegans T23G5.5
    Homologene
    FAMILY
  • solute carrier family 6, 5-hydroxytryptamine, serotonin
  • sodium:neurotransmitter symporter (SNF) family
    • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • terminating the action of serotonin by its high affinity sodium-dependent reuptake into presynaptic terminals
  • exquisitely sensitive to the cholesterol content of membranes
  • potentially playing a role in heart valve development and disease
  • membrane-bound transporter of serotonin that influences extracellular levels of this neurotransmitter
  • involved in the modulation of activity-dependent mechanisms during the wiring of sensory circuits
  • plays a crucial role in synaptic neurotransmission by retrieving released serotonin
  • SLC6A3, SLC6A2, SLC6A4 facilitate the homeostatic balance of neurotransmitters in the synaptic cleft and thus, play a fundamental role in regulating neuronal activity
  • regulates the extracellular concentration of serotonin, influencing neurotransmission
  • is responsible for the termination of synaptic serotonergic signaling
  • might disrupt efferocytosis and contribute to the pathogenesis of autoimmune and chronic inflammatory diseases
  • plays a critical role in regulating serotonin signaling by mediating reuptake of serotonin from the extracellular space
  • terminates serotonergic neurotransmission by performing reuptake of released serotonin, and is the primary target for antidepressants
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS active transport
    text sodium/chlorine Na+/Cl- coupled transporter of serotonin
    PATHWAY
    metabolism
    signaling neurotransmission
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Na+
  • Cl-
    • protein
  • interactions with ITGB3 playing a role in autism etiology and in serotonin level determination
  • interacting with ROBO1, ROBO2
  • important interactive relationship between SLC6A4 and the PDGFRB in the production of pulmonary artery smooth muscle cell proliferation triggered by PDGF that may be important in pulmonary hypertension (PH)
  • interaction between SLC6A4 and the Secretory Carrier Membrane Protein 2 (SCAMP2)
  • interacting with SEC24C (can only exit the ER by recruiting SEC24C)
  • involvement of ERP44 in maturation of SLC6A4
  • ERP44 together with ERO1A plays an important role in disulfide formation of SLC6A4, which may be a prerequisite step for the assembly of SLC6A4 molecules in oligomeric form
  • utilizes ERP44 as well as its partner ERO1A, an oxidoreductase, in the disulfide bond formation process
  • novel role of HDAC2 as a regulator of SLC6A4 gene expression in intestinal epithelial cells
  • IL10 modulates SLC6A4 activity and expression in intestinal epithelial cells, depending on its extracellular conditions
  • impairment of SLC6A4 may affect BDNF expression throughout postnatal development
  • ITGB3 is a modulator of serotonergic systems via genetic interactions with the 5-HT transporter gene (SLC6A4)
  • physical association of SLC6A4 with PPP3CA is promoted by PPP3CA activity
  • TGFB1 increased the association of SLC6A4 with the soluble STX3 and promoted exocytosis of SLC6A4
  • is epigenetically downregulated by HDAC1 in several types of cancer
  • SLC6A4 associates with SLC1A5, co-expressed with SLC6A4 in serotonergic neurons and involved in the transport of small neutral amino acids across the plasma membrane
    • cell & other
    REGULATION
    Other psychomotor stimutants such as amphetamines,cocaine or antidepressant
    is constitutively internalized and that the internalized transporter is sorted mainly to degradation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to sudden infant death
  • a possible association to bipolar affective disorder and personality traits in a primarily female population sample
  • susceptibility gene for high cholesterol and heart disease
  • susceptibility to major depression, to attention deficit hyperactivity disorder, to autism and rigid-compulsive behaviors
  • to obsessive-compulsive disorder(OCD)
    • Variant & Polymorphism other
  • some evidence of allelic variation modulating anxiety-related traits
  • promoter polymorphism increasing the risk of sudden infant death (L/L)
  • L(A) allele was twofold overtransmitted to the patients with OCD
  • a 44-bp insertion/deletion polymorphism in the upstream regulatory region (5-HTTLPR) and a VNTR polymorphism in the second intron (Stin2) increasing the risk of SIDS
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    psychiatryautism 
    major therapeutic target in autism
    psychiatrybipolar disorder 
    common targets of drugs extensively used for the treatment of multiple different pathologies, ranging from anorexia, depression, anxiety and other psychiatric as well as neurological disorders to gastrointestinal and uro-genital dysfunctions
    ANIMAL & CELL MODELS
  • Sert(-/-) rats show decreased brain-derived neurotrophic factor (Bdnf) expression, as well as reduced levels of transcription factor regulating the neurotrophin transcription