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FLASH GENE
Symbol SLC22A3 contributors: mct/npt - updated : 07-10-2015
HGNC name solute carrier family 22 (extraneuronal monoamine transporter), member 3
HGNC id 10967
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • twelve transmembrane domains (12TM)
  • cytoplasmic N and C termini
  • one nucleotide (ATP/GTP) binding site motif
    • HOMOLOGY
    Homologene
    FAMILY
  • major facilitator superfamily
  • organic cation transporter family
  • solute carrier family 22, extraneuronal monoamine
    • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
    text to the basolateral membrane (BLM) (Glube 2008)
    basic FUNCTION
  • polyspecific transporter of organic cations, sodium independent
  • playing a key role in the clearance of monoamines from extracellular compartments (Bottalico 2007)
  • can potentially regulate reuptake of monoamines in general and histamine in particular (Bottalico 2007)
  • participate in the renal secretion of several therapeutic agents, and interacts with renally secreted drugs (Glube 2008)
  • may modulate dopaminergic damage by bidirectionally regulating the local bioavailability of exogenous and endogenous toxic species (Cui 2009)
  • pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway (Cui 2009)
  • functions as a cation transporter in various organs, including prostate tissue, and plays a role eliminating small organic cations and toxins
  • NUDT11, SLC22A3, HNF1b contribute to prostate cancer pathogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS facilitated diffusion transport
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
    REGULATION
    Other regulated by phosphorylation/dephosphorylation mechanisms, active in the dephosphorylated state
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    lower expression of mRNAs in pre-eclamptic placentae as compared to the control group (Bottalico 2004)
    tumoral     --low  
    inversely correlated with Prostate carcinoma progression, with reduced expression as disease advances
    constitutional     --over  
    of SLC22A3 and SLC47A1 in human placenta indicates these transporters may play a role in fetal protection preferentially at earlier stages of gestation
    Susceptibility
  • to coronary artery disease
  • to the development of polysubstance use in Japanese patients with Methamphetamine (MAP) dependence
  • to euphoria and potential for addiction and susceptibility to the toxicity of substances of abuse
    • Variant & Polymorphism SNP
  • four SNPs overlapping the SLC22A3-LPAL2-LPA gene cluster associated to risk of coronary artery disease (Tregouet 2009)
  • polymorphisms of SLC22A3 related to the development of polysubstance use in Japanese patients with MAP dependence (Aoyama 2006)
  • polymorphisms may reduce or inactivate the function of SLC22A3 and therefore enhance the euphoria and potential for addiction and susceptibility to the toxicity of substances of abuse (Cui 2009)
    • Candidate gene
    Marker
    Therapy target Monoamine transporters may serve as a protective mechanism preventing vasoconstriction in the placental vascular bed and thereby securing a stable blood flow to the fetus (Bottalico 2004)
    ANIMAL & CELL MODELS