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FLASH GENE
Symbol SLC47A1 contributors: mct/npt/pgu - updated : 15-05-2024
HGNC name solute carrier family 47, member 1
HGNC id 25588
Location 17p11.2      Physical location : 19.437.166 - 19.482.346
Synonym name multidrug and toxin extrusion 1
Synonym symbol(s) FLJ10847, MATE1, MGC64822
DNA
TYPE functioning gene
STRUCTURE 45.18 kb     17 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 3279 - 570 - 2009 19172157
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestine     Homo sapiens
 liver     Homo sapiens
Urinarykidneytubuleconvoluted tubuleproximal tubule  Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialabsorptive excretoryrenal tubular epithelium   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Urinaryepithelial cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • extracellular C terminus with 13, not 12, transmembrane helices, but the 13th TMH is not necessary for transport function, but it may influence turnover activity of the transporter
    • HOMOLOGY
    Homologene
    FAMILY
  • multidrug and toxic compound extrusion (MATE) proteins family
    • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • highly expressed in peroxisomes and the endoplasmic reticulum (ER) as well as in plasma membranes
  • expressed at the brush-border membranes
    • basic FUNCTION
  • mediates H(+)-coupled electroneutral exchange of tetraethylammonium and 1-methyl-4-phenylpyridinium
  • function together as a detoxication system, by mediating the tubular secretion of intracellular ionic compounds across the brush-border membranes of the kidney
  • play important roles in the renal tubular secretion of cationic drugs
  • able to transport tetraethylammonium (TEA) utilizing an oppositely directed H+ gradient as a driving force
  • play crucial roles in the renal handling of cationic drugs, such as cimetidine, metformin and oxaliplatin
  • SLC47A1 and SLC22A2 are transport systems that may be of importance for the cellular disposition of agmatine and putrescin
  • mediates renal organic cation secretion
  • SLC47A1, SLC47A2, are critical players in the luminal export of organic cations (OCs) from renal proximal tubule cells in human kidney
  • mediates drug secretion into urine at the brush-border membranes
  • H(+)-coupled organic cation exporter responsible for the final step of excretion of various xenobiotics at the kidney and liver
  • membrane transporter for flavonoids and has a high affinity for quercetin
  • membrane transporters mediating the excretion of organic cations and zwitterions into bile and urine and thereby contributing to the hepatic and renal elimination of many xenobiotics
  • is a H+/organic cation (OC) exchanger responsible for the final step of toxic organic cation excretion in the kidney and liver
  • likely Glu273 of SLC47A1 plays essential roles in substrate binding and transport
  • SLC47A1 but not SLC47A2 is involved in human testosterone transport
  • regulator of lipid remodeling and survival during ferroptosis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • coordinate function of SLC47A1 with SLC22A2 likely contributes to the vectorial renal elimination of organic cationic drugs
  • DDAH1 and L-arginine are substrates of human SLC7A2, SLC22A2, SLC47A1
  • is a membrane transporter for quercetin
  • PPARA is a transcription factor that transactivates SLC47A1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    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
    constitutional       loss of function
    caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis
    Susceptibility
  • to drug-induced nephrotoxicity
  • to variation of metformin response in type 2 diabetes
    • Variant & Polymorphism SNP
  • significant decrease in transport activity, and especially G64D were completely abolished by the impairment of cell surface expression leading to drug-induced nephrotoxicity
  • nonsynonymous variants in hMATE1 may alter drug disposition and ultimately affect clinical drug response
  • patients with A allele had highest HbA1C reduction in response to metformin
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS