Affinage

SLC47A1

Multidrug and toxin extrusion protein 1 · UniProt Q96FL8

Length
570 aa
Mass
61.9 kDa
Annotated
2026-06-10
95 papers in source corpus 35 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC47A1 (MATE1) is a proton-coupled antiporter that mediates the final efflux step of cationic drugs, endogenous metabolites, and toxins across the apical (luminal) membranes of renal proximal tubule and hepatic epithelia, where an outwardly directed H+ gradient drives electroneutral organic cation/H+ exchange (PMID:16641166, PMID:17047166, PMID:16850272). It works coordinately with basolateral OCT-family uptake transporters (OCT1/OCT2/OCT3): OCTs load substrates into the cell and MATE1 extrudes them across the apical face, generating vectorial transepithelial secretion in polarized monolayers, kidney, and placenta (PMID:20883471, PMID:22543277, PMID:26538438). The transporter recognizes an unusually broad substrate range — prototypical cations such as TEA and MPP+, metformin, cimetidine, the zwitterion cephalexin, oxaliplatin, cisplatin, agmatine, ADMA, TMAO, and flavonoids including quercetin — and renal/placental secretion of metformin, cisplatin, and oxaliplatin depends on MATE1 in vivo, such that its loss potentiates cisplatin nephrotoxicity (PMID:19332510, PMID:20813096, PMID:34959286, PMID:17582384). Structurally, the functional core comprises 12 transmembrane helices (a thirteenth helix tuning turnover rather than selectivity), and cryo-EM and reconstitution work localize substrate binding to a negatively charged pocket in the C-lobe where Glu273 is essential for binding and Glu278 for transport (PMID:18305230, PMID:22722930, PMID:30028956, PMID:41145429). MATE1 expression is set by transcriptional inputs (AP-1/AP-2rep, Nkx-2.5/SREBP-1/USF-1, and PPARα) and by CpG-island DNA methylation, a control co-opted by mutant KRAS via DNMT1 to silence the gene in colorectal cancer (PMID:19745787, PMID:29070695, PMID:32444490, PMID:31963528, PMID:23558289). Beyond solute transport, MATE1 acts as a lipid flippase that remodels membrane lipid composition and limits ferroptosis: its loss favors ACSL4/SOAT1-driven accumulation of polyunsaturated fatty acid cholesterol esters, and the PPARA–SLC47A1 axis governs lipid-peroxidation-mediated cell death (PMID:36575162).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 High

    Established the core identity of MATE1 as an electroneutral H+/organic cation exchanger at the luminal membranes that perform final excretion of toxic cations, defining its physiological role in kidney and bile.

    Evidence Heterologous expression in HEK293 cells with organic cation transport assays and subcellular localization

    PMID:16641166

    Open questions at the time
    • Driving force not yet directly demonstrated
    • Substrate-binding residues unidentified
  2. 2006 High

    Defined the energetic driving force, showing an outwardly directed H+ gradient (not membrane potential) powers transport, and that activity is pH-dependent with maximal exchange at alkaline pH.

    Evidence Plasma membrane vesicle transport assays with [14C]TEA, FCCP and valinomycin controls; pH-varied uptake in HEK293 cells

    PMID:16850272 PMID:17047166

    Open questions at the time
    • Transport stoichiometry for divalent substrates not resolved
    • Structural basis of H+ coupling unknown
  3. 2008 High

    Identified specific glutamate residues mediating substrate recognition and transport, with Glu278 essential for activity, beginning the mechanistic map of the binding/translocation machinery.

    Evidence Site-directed mutagenesis of Glu residues with TEA/cimetidine transport assays and surface biotinylation in HEK293 cells

    PMID:18305230

    Open questions at the time
    • Relative contributions of binding vs translocation not separated
    • No structural context for the residues
  4. 2009 High

    Resolved membrane topology (13 TMHs with extracellular C-terminus, TMH13 dispensable for binding) and demonstrated in vivo physiological necessity through knockout pharmacokinetics of metformin.

    Evidence Epitope/cysteine-scanning topology probes with truncations; Mate1 knockout mouse metformin pharmacokinetics

    PMID:19332510 PMID:19515813

    Open questions at the time
    • Functional core helix count not yet finalized
    • Role of TMH13 in turnover only partially defined
  5. 2009 Medium

    Linked human genetic variation to transport function, showing coding (G64D, D328A) and promoter (g.-66T>C) variants reduce surface expression or transcription, connecting MATE1 genotype to drug-elimination capacity.

    Evidence Variant expression with transport/biotinylation assays; luciferase reporters, EMSA, and kidney qPCR in genotyped subjects

    PMID:19158817 PMID:19745787

    Open questions at the time
    • Clinical pharmacokinetic consequences not established in these studies
    • Single-lab functional characterization
  6. 2010 High

    Demonstrated the OCT-MATE relay produces directional transepithelial secretion and that MATE1 protects the kidney by exporting cisplatin, establishing its role in drug-induced nephrotoxicity.

    Evidence Double-transfected OCT/MATE1 MDCK monolayers with pH-dependent transcellular assays; Mate1 knockout plus pyrimethamine inhibition in cisplatin-treated mice

    PMID:20053795 PMID:20813096 PMID:20883471

    Open questions at the time
    • Quantitative contribution of each OCT partner in vivo not resolved
    • Cisplatin transport mechanism vs accumulation not fully dissected
  7. 2013 Medium

    Broadened the substrate scope to endogenous metabolites (agmatine, ADMA, L-arginine) and refined the functional core to 12 TMHs validated by a NorM-based homology model, indicating physiological metabolite handling beyond xenobiotics.

    Evidence Kinetic uptake assays in MATE1-HEK293 cells; truncation mutagenesis, transport assays, and molecular dynamics simulation

    PMID:21128598 PMID:22722930 PMID:23864433

    Open questions at the time
    • Physiological significance of endogenous substrate transport unquantified in vivo
    • Homology model not yet replaced by experimental structure
  8. 2014 High

    Showed MATE1 functions in placental cation elimination paired with OCT3, and identified additional substrate classes (flavonoids/quercetin), expanding its tissue and substrate breadth.

    Evidence Dually perfused rat placenta with localization and inhibition; MATE1 overexpression/knockdown with quercetin uptake and subcellular imaging

    PMID:22543277 PMID:25241911

    Open questions at the time
    • Placental relevance later found to be species-restricted
    • Intracellular quercetin accumulation mechanism uncharacterized
  9. 2015 High

    Distinguished intracellular V-ATPase-dependent sequestration of cations from apical secretion, showing endosomal sequestration raises steady-state accumulation but does not drive the rate of luminal efflux.

    Evidence Efflux kinetics and bafilomycin treatment in MATE1-CHO cells; isolated nonperfused and perfused rabbit proximal tubules

    PMID:26538438

    Open questions at the time
    • Identity of the acidified compartment not definitively assigned
    • Generality across substrates untested
  10. 2017 High

    Established epigenetic control of MATE1 expression through a 5' CpG-island enhancer, where DNA methylation tunes hepatic expression up to ~20-fold.

    Evidence Bisulfite sequencing of human liver, 5-aza demethylation, reporter assays, and CRISPR deletion of the CpG island in HepG2

    PMID:29070695

    Open questions at the time
    • Trans-acting factors reading the methylation state not identified
    • Tissue specificity of the enhancer not fully mapped
  11. 2020 Medium

    Connected MATE1 regulation to oncogenic and nuclear-receptor signaling: mutant KRAS silences MATE1 via DNMT1-driven promoter methylation, and PPARα transcriptionally controls renal MATE1, integrating its expression into metabolic and disease pathways.

    Evidence KRAS-mutant CRC cells/PDX with metformin accumulation and methylation analysis; PPARα knockout mice and agonist/antagonist treatment with Western/qPCR

    PMID:31963528 PMID:32444490 PMID:33049997

    Open questions at the time
    • Apparently opposing PPARα effects across studies not reconciled
    • Single-lab models for each regulatory axis
  12. 2018 High

    Provided definitive biochemical mechanism by purifying and reconstituting MATE1 in proteoliposomes, establishing electroneutral transport with charge-dependent electrogenicity and Glu273 as the essential binding residue.

    Evidence Purification from insect cells, liposome reconstitution, radiolabeled transport, ligand binding, and E273Q mutagenesis

    PMID:30028956

    Open questions at the time
    • Atomic structure not yet available at this stage
    • Conformational cycle not visualized
  13. 2022 High

    Revealed a non-transport function: MATE1 acts as a lipid flippase that remodels membrane lipids to limit ferroptosis, with the PPARA-SLC47A1 axis controlling PUFA-cholesterol-ester accumulation and lipid-peroxidation cell death.

    Evidence siRNA silencing with lipidomics, ferroptosis induction, PPARA knockdown plus SLC47A1 rescue, and in vivo tumor model

    PMID:36575162

    Open questions at the time
    • Direct lipid-flipping activity not reconstituted biochemically
    • Relationship between flippase and cation-transport functions unresolved
  14. 2025 High

    Delivered atomic-resolution understanding via cryo-EM structures of MATE1 bound to MPP, metformin, and cimetidine, localizing a shared negatively charged C-lobe binding pocket and resolving ligand-specific binding modes.

    Evidence Cryo-EM structure determination with mutant uptake assays and molecular dynamics

    PMID:41145429

    Open questions at the time
    • Full proton-coupled transport cycle conformations not all captured
    • Lipid-flippase conformation not structurally defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the same protein reconciles broad organic-cation/H+ antiport with its lipid-flippase activity, and which structural states underlie each function, remains unresolved.
  • No structure of MATE1 engaged with a lipid substrate
  • No biochemical reconstitution of flippase activity
  • Functional interdependence of the two activities untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0140104 molecular carrier activity 4 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 5 GO:0005768 endosome 1 GO:0005777 peroxisome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-382551 Transport of small molecules 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-9748784 Drug ADME 4 R-HSA-5357801 Programmed Cell Death 1
Partners
SLC22A1SLC22A2SLC22A3

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Human MATE1 (SLC47A1) mediates electroneutral H+/organic cation exchange at the luminal membranes of renal proximal tubules and bile canaliculi, responsible for the final excretion step of toxic organic cations into urine and bile. Heterologous expression in HEK293 cells, transport assays with prototypic organic cations, subcellular localization studies American journal of physiology. Cell physiology High 16641166
2006 An oppositely directed H+ gradient (outwardly directed from vesicle interior) serves as the driving force for MATE1-mediated tetraethylammonium transport, demonstrated definitively using plasma membrane vesicles from HEK293 cells stably expressing rat MATE1; the transport showed an overshoot phenomenon dependent on the H+ gradient and was sensitive to the protonophore FCCP but not to valinomycin-induced membrane potential. Plasma membrane vesicle transport assays with [14C]tetraethylammonium, protonophore (FCCP) and ionophore (valinomycin) treatments, inside-out gradient experiments American journal of physiology. Renal physiology High 17047166
2006 Rat MATE1 is expressed in renal proximal convoluted and straight tubules (not liver), transports organic cations (TEA, cimetidine, metformin) and the zwitterion cephalexin via an H+-gradient-dependent antiport mechanism; transport activity is maximal at alkaline pH and stimulated by intracellular acidification. PCR cloning, transient expression in HEK293 cells, transport assays at varying pH, ammonium chloride-induced acidification, Northern blot and real-time PCR of microdissected nephron segments Pharmaceutical research High 16850272
2006 Mouse MATE1 mediates electroneutral H+/tetraethylammonium exchange and is expressed not only in kidney and liver but also in brain glia-like cells and capillaries, pancreatic duct cells, urinary bladder epithelium, adrenal cortex, alpha cells of islets, Leydig cells, and hepatic Ito cells. Expression in HEK293 cells with transport assays, immunological techniques with specific antibodies, RT-PCR American journal of physiology. Cell physiology Medium 16641166
2008 Glutamate residues Glu273, Glu278, Glu300, and Glu389 in transmembrane regions of human MATE1 are involved in substrate recognition and transport; Glu278Ala mutation completely abolished TEA transport activity; other Glu mutations altered substrate affinities and pH dependence, indicating distinct roles for each residue. Site-directed mutagenesis, expression in HEK293 cells, transport assays with TEA and cimetidine, cell surface biotinylation American journal of physiology. Cell physiology High 18305230
2009 Rabbit MATE1 has an extracellular C-terminus consistent with 13 transmembrane helices (TMHs); TMH13 is not necessary for transport function but influences transporter turnover rate; truncation mutants lacking TMH13 show similar Kt and Jmax but reduced transport rate per surface-expressed protein. Epitope tagging with V5 at C-terminus and internal truncation sites, antibody accessibility assays with and without membrane permeabilization, cysteine scanning with maleimide-PEO2-biotin, transport assays American journal of physiology. Renal physiology High 19515813
2009 MATE1 knockout mice show markedly reduced renal secretion of metformin: renal clearance and renal secretory clearance were ~18% and ~14% of wild-type values, respectively, demonstrating an essential role for MATE1 in systemic metformin clearance. Targeted gene disruption in mice, intravenous pharmacokinetic study with metformin, plasma concentration-time curve analysis, urinary excretion measurement Molecular pharmacology High 19332510
2009 MATE1 coding SNPs G64D and D328A reduce cell surface membrane expression of MATE1 protein; G64D completely abolishes transport activity; these loss-of-function variants alter renal drug elimination capacity. Sequencing of MATE1 exons in human subjects, expression of variants in cells, transport assays, cell surface biotinylation to assess membrane expression Journal of human genetics Medium 19158817
2009 Promoter variant g.-66T>C of MATE1 reduces transcriptional activity by decreasing binding of transcriptional activator AP-1 and enhancing binding of repressor AP-2rep; individuals homozygous or heterozygous for g.-66T>C have significantly lower MATE1 mRNA expression in kidney. Luciferase reporter assays in vitro and in vivo, electrophoretic mobility shift assays (EMSA), qPCR of kidney tissue from human subjects with known genotypes Pharmacogenetics and genomics High 19745787
2010 MATE1 loss-of-function variants (c.404T>C p.T159M and c.1012G>A p.V338A) show significant loss of transport activity for metformin and tetraethylammonium; coordinated function of MATE1 with OCT2 contributes to vectorial renal elimination of organic cationic drugs. Vaccinia virus expression system, double-transfected OCT2/MATE1 cells, transport assays, genetic polymorphism functional characterization American journal of physiology. Renal physiology Medium 20053795
2010 MATE1 disruption in mice potentiates cisplatin-induced nephrotoxicity: Mate1(-/-) mice have shorter lifespan, higher plasma creatinine/BUN, and greater renal accumulation of cisplatin after administration, demonstrating that MATE1 mediates efflux of cisplatin from renal cells. Mate1 knockout mice, cisplatin administration, pharmacokinetic analysis, renal function markers (creatinine, BUN), pharmacological inhibition with pyrimethamine Biochemical pharmacology High 20813096
2010 Double-transfected MDCK cells expressing OCT2/MATE1 or OCT1/MATE1 show significantly higher basal-to-apical transcellular transport of metformin and MPP+ compared to single-transfected cells, demonstrating functional interplay between OCT-mediated uptake and MATE1-mediated efflux for vectorial transport; MATE1 function is pH-sensitive, with decreasing transport at higher luminal pH. Single- and double-transfected MDCK cell monolayers, concentration- and pH-dependent transcellular transport assays British journal of pharmacology High 20883471
2010 Human MATE1 transports agmatine in an H+/organic cation exchange manner that is saturable (Km = 240 μM), trans-stimulated by inward proton gradient, and inhibited by polyamines and prototypical cation substrates but not by L-arginine. Stable transfection of HEK293 cells with hMATE1, [3H]agmatine uptake assays, pH-dependence studies, inhibition studies Molecular pharmaceutics Medium 21128598
2012 The functional core of mammalian MATE1 consists of 12 (not 13) transmembrane helices; TMH13 has little impact on ligand binding or substrate selectivity but may influence substrate translocation rate; a homology model based on the NorM crystal structure was developed and validated by molecular dynamics. C-terminal epitope tagging, antibody accessibility assays, truncation mutagenesis at Gly-545, transport assays, CHO cell expression, molecular dynamics simulations The Journal of biological chemistry High 22722930
2012 OCT3 and MATE1 form a coordinated transplacental eliminatory pathway in rat placenta: OCT3 localizes to the basolateral (fetus-facing) side and takes up organic cations from fetal circulation, while MATE1 localizes to the apical (maternal-facing) side and mediates efflux from placenta to maternal circulation, enabling net fetal-to-maternal transport of MPP+ even against a concentration gradient. qRT-PCR, Western blotting, immunohistochemistry, dually perfused rat term placenta in situ method (open- and closed-circuit), pharmacological inhibition Toxicological sciences High 22543277
2013 MATE1 and OCT3 mediate transplacental transfer of metformin in rat placenta; the opposing H+ gradient drives MATE1-mediated secretion of metformin from placenta to maternal circulation; transport is completely inhibited by MPP+. Dually perfused rat placenta model, concentration-dependent clearance measurements, pharmacological inhibition, H+ gradient manipulation Reproductive toxicology Medium 23562376
2013 MATE1 transports asymmetric dimethylarginine (ADMA) and L-arginine in a pH-dependent manner (greater uptake at alkaline pH), identifying ADMA as a substrate relevant to renal/hepatic elimination. Stable HEK293 cells overexpressing MATE1, concentration- and pH-dependent [3H]ADMA and [3H]L-arginine uptake assays, kinetic parameter determination Amino acids Medium 23864433
2014 MATE1 functions as a flavonoid transporter with high affinity for quercetin; in HepG2 and HEK293T cells overexpressing MATE1, quercetin accumulates in peroxisomes and the endoplasmic reticulum as well as plasma membrane; MATE1 inhibition or knockdown reduces quercetin uptake. MATE1 overexpression in HEK293T cells, MATE1 inhibition and shRNA knockdown in HepG2 cells, immunofluorescence, fluorescent microscopy with peroxisome markers Journal of agricultural and food chemistry Medium 25241911
2015 MATE1 sequesters organic cations in an intracellular V-type H+-ATPase-acidified compartment (punctate, likely endosomal) in CHO cells; this intracellular sequestration, dependent on bafilomycin-sensitive V-ATPase, increases steady-state OC accumulation in renal proximal tubule cells but does NOT contribute to the rate of apical OC secretion in perfused rabbit proximal tubules. Epifluorescence microscopy, efflux kinetics of [3H]MPP in MATE1-expressing CHO cells, bafilomycin (V-ATPase inhibitor) treatment, isolated nonperfused and perfused rabbit renal proximal tubule experiments American journal of physiology. Renal physiology High 26538438
2017 DNA methylation in the 5' CpG island of SLC47A1 negatively correlates with MATE1 mRNA expression in human liver (~20-fold variability); demethylation with 5-aza-2'-deoxycytidine increases MATE1 expression; the CpG island acts as a transcriptional enhancer; CRISPR knockout of the CpG island reduces MATE1 expression. Bisulfite sequencing of human liver samples, 5-aza-2'-deoxycytidine treatment, luciferase reporter assays, CRISPR-Cas9 CpG island deletion in HepG2 cells, correlation analysis of methylation vs expression Molecular pharmacology High 29070695
2018 Purified and reconstituted human MATE1 in proteoliposomes mediates ΔpH-dependent, electroneutral uptake of [14C]TEA; divalent substrate transport is electrogenic (OC/H+ stoichiometry independent of substrate charge); Glu273Gln mutation completely abolishes TEA binding and transport, identifying Glu273 as essential for substrate binding. Expression in insect cells, detergent solubilization, purification, reconstitution into liposomes, radiolabeled transport assays, site-directed mutagenesis (E273Q), ligand binding in lipid-detergent micelles Biochimica et biophysica acta. Biomembranes High 30028956
2018 MATE1 contributes to renal secretion of TMAO; transcellular transport of TMAO is significantly increased in polarized MDCK monolayers expressing MATE1 (not detected in non-polarized HEK-MATE1 cells), demonstrating that directional transport requires cellular polarity and that non-polarized uptake assays can give false-negative results for certain MATE1 substrates. HEK293 cells and polarized MDCK monolayers stably expressing MATE1 or OCT2, transcellular TMAO transport assays, trimethoprim inhibition Scientific reports Medium 29704007
2019 MATE1 protein localizes to the apical side of bronchial and bronchiolar epithelial cells and is strongly expressed in alveolar macrophages and inflammatory T cells in human lung. Immunohistochemistry in human lung tissue from healthy subjects and COPD patients, qPCR in lung tissue and BAL cells Respiratory research Medium 29678179
2020 Mutant KRAS oncoprotein epigenetically silences MATE1 expression in colorectal cancer cells by upregulating DNA methyltransferase 1 (DNMT1), leading to hypermethylation of the MATE1 promoter; this reduces metformin efflux, causing intracellular accumulation of metformin preferentially in KRAS-mutant cells. Primary cell cultures and patient-derived xenografts, metformin accumulation assays, DNMT1 expression analysis, DNA methylation analysis, genetic and pharmacological manipulation Proceedings of the National Academy of Sciences of the United States of America Medium 32444490
2020 PPAR-α deletion protects against cisplatin nephrotoxicity and restores MATE-1 expression in kidney; at baseline, PPAR-α knockout mice show increased MATE-1 and reduced OCT-2 expression, indicating PPAR-α negatively regulates MATE-1 expression. PPAR-α knockout mice, cisplatin administration, Western blot for MATE-1 and OCT-2 protein, renal function and injury markers International journal of molecular sciences Medium 33049997
2020 PPAR-α transcriptionally upregulates MATE-1 expression in the kidney: metformin treatment increases MATE-1 expression in a PPARα-dependent manner; PPARα antagonist (MK-886) reduces MATE-1 expression; PPARα agonist (gemfibrozil) increases MATE-1 expression 376%; PPARα knockout mice fail to upregulate MATE-1 upon metformin treatment. Wild-type and PPARα knockout mice, kidney tubular cell line, PPARα agonist/antagonist treatment, Western blot and qPCR Molecules Medium 31963528
2021 Of 57 FDA-approved TKIs evaluated, 37 potently inhibit MATE1 function by >80% through a non-competitive, reversible, substrate-independent mechanism; MATE1 deficiency reduces urinary excretion of oxaliplatin ~2-fold in mice, establishing MATE1 as mediating renal secretion of oxaliplatin. Transfected HEK293 cells, inhibition assays with 57 TKIs, in vivo pharmacokinetic studies in wild-type, MATE1-deficient, and OCT2/MATE1-double-deficient mice Pharmaceutics High 34959286
2022 SLC47A1/MATE1 functions as a lipid flippase that remodels membrane lipid composition; its silencing increases ferroptosis sensitivity by favoring ACSL4-SOAT1-mediated production of polyunsaturated fatty acid cholesterol esters (PUFA-CEs); PPAR-α transcriptionally transactivates SLC47A1, and PPARA-SLC47A1 axis determines lipid peroxidation-mediated cell death. siRNA silencing of SLC47A1, large-scale lipidomics, RSL3/erastin-induced ferroptosis assays, PPARA knockdown and SLC47A1 re-expression rescue experiments, in vivo mouse tumor model with ferroptosis inducer Nature communications High 36575162
2022 Transport turnover rates (TOR) for human MATE1 are substrate-dependent: ~84 s-1 for MPP, ~461 s-1 for metformin; surface-expressed MATE1 protein represents ~25% of total cellular MATE1 in CHO cells (~55 fmol/cm2), determined by quantitative western blot with cell surface biotinylation. Cell surface biotinylation, quantitative western blot with V5-epitope standard curves, Jmax from transport assays divided by surface protein quantity International journal of molecular sciences Medium 35163393
2025 Cryo-EM structures of human MATE1 in complex with MPP, metformin, and cimetidine reveal a shared binding site in a negatively charged pocket in the C-lobe of the protein; key binding residues were functionally validated by mutagenesis; molecular dynamics simulations reveal different binding modes and dynamics for each ligand. Cryo-electron microscopy structure determination, radioactivity-based cellular uptake assays with MATE1 mutants, molecular dynamics simulations Nature communications High 41145429
2007 Human MATE1 and rMATE1 mediate H+-gradient-dependent antiport of oxaliplatin but not cisplatin; carboplatin and nedaplatin are not transported by MATE transporters; OCT2 mediates uptake of cisplatin and oxaliplatin into renal cells. Expression in cells with H+ gradient-dependent transport assays for platinum compounds Biochemical pharmacology Medium 17582384
2008 Ischemia/reperfusion-induced acute kidney injury in rats causes down-regulation of luminal rMATE1 protein expression, contributing to decreased urinary secretion of organic cations (TEA) and higher plasma exposure. Ischemia/reperfusion rat model, Western blot for rMATE1 and rOCT2 protein, pharmacokinetic analysis of famotidine and TEA, renal slice accumulation assays Drug metabolism and disposition Medium 18180268
2013 MATE1 promoter variant g.-1975C>A increases transcriptional activity through enhanced binding of transcription factors Nkx-2.5, SREBP-1, and USF-1; Nkx-2.5 and USF-1 were identified as inducers of MATE1 transcription. Luciferase reporter assays, electrophoretic mobility shift assays (EMSA), transcription factor prediction and validation Biochemical and biophysical research communications Medium 23558289
2017 MATE1 mediates cellular uptake of imatinib with higher affinity than OCT1; MATE1 expression is reduced in bone marrow cells of imatinib-non-responding CML patients compared to responders, indicating MATE1 controls intracellular imatinib availability and determines therapeutic response. Transport assays in cells expressing MATE1, comparison of MATE1 expression in bone marrow cells of CML patients stratified by treatment response Blood cancer journal Medium 27635733
2018 Crizotinib inhibits MATE1-mediated creatinine transport in a time-dependent, non-competitive manner (Ki values of 0.342-2.34 μM depending on pre-incubation conditions), with inhibitory potency increasing with incubation time, consistent with slow-tight binding kinetics. MATE1-overexpressing cells, [14C]creatinine and [3H]MPP+ uptake assays, pre-incubation vs co-incubation experiments, kinetic analysis Scientific reports Medium 29915248
2025 MATE1 shows almost exclusive expression in rat placental labyrinth but is minimally or undetectably expressed in human and mouse placental villi/labyrinth; functional MATE1 in rat placenta contributes to low fetal transfer of metformin and MPP+ in rats (F/M ratios increased ~50% by pyrimethamine-mediated MATE1 inhibition in rats but not mice). RNA-sequencing, absolute protein quantification by LC-MS/MS, in vivo pharmacokinetic studies in pregnant rats and mice with and without pyrimethamine (selective MATE1 inhibitor), IC50 determination for pyrimethamine against rat MATE1 and OCT3 Molecular pharmaceutics High 41184726

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Aluminum tolerance in maize is associated with higher MATE1 gene copy number. Proceedings of the National Academy of Sciences of the United States of America 194 23479633
2007 Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity. Biochemical pharmacology 185 17582384
2010 Disruption of multidrug and toxin extrusion MATE1 potentiates cisplatin-induced nephrotoxicity. Biochemical pharmacology 169 20813096
2012 The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin. Clinical pharmacology and therapeutics 140 23267855
2009 Targeted disruption of the multidrug and toxin extrusion 1 (mate1) gene in mice reduces renal secretion of metformin. Molecular pharmacology 133 19332510
2010 Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. American journal of physiology. Renal physiology 117 20053795
2022 The lipid flippase SLC47A1 blocks metabolic vulnerability to ferroptosis. Nature communications 116 36575162
2010 Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenetics and genomics 103 19898263
2012 Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes. Diabetes, obesity & metabolism 91 22882994
2011 Double-transfected MDCK cells expressing human OCT1/MATE1 or OCT2/MATE1: determinants of uptake and transcellular translocation of organic cations. British journal of pharmacology 86 20883471
2006 Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharmaceutical research 85 16850272
2006 Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations. American journal of physiology. Cell physiology 76 16641166
2015 Inhibitory Effects of Green Tea and (-)-Epigallocatechin Gallate on Transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-Glycoprotein. PloS one 74 26426900
2020 Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1. Proceedings of the National Academy of Sciences of the United States of America 67 32444490
2013 A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin. Pharmacogenetics and genomics 66 23873119
2009 Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity. Journal of human genetics 63 19158817
2018 Effect of tyrosine kinase inhibitors on renal handling of creatinine by MATE1. Scientific reports 62 29915248
2006 Oppositely directed H+ gradient functions as a driving force of rat H+/organic cation antiporter MATE1. American journal of physiology. Renal physiology 59 17047166
2010 OCT2 and MATE1 provide bidirectional agmatine transport. Molecular pharmaceutics 51 21128598
2008 Altered pharmacokinetics of cationic drugs caused by down-regulation of renal rat organic cation transporter 2 (Slc22a2) and rat multidrug and toxin extrusion 1 (Slc47a1) in ischemia/reperfusion-induced acute kidney injury. Drug metabolism and disposition: the biological fate of chemicals 50 18180268
2016 The Effect of Famotidine, a MATE1-Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin. Clinical pharmacokinetics 44 26597253
2013 Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1). Amino acids 44 23864433
2015 SLC47A1 gene rs2289669 G>A variants enhance the glucose-lowering effect of metformin via delaying its excretion in Chinese type 2 diabetes patients. Diabetes research and clinical practice 43 26004431
2009 Identification and characterization of novel polymorphisms in the basal promoter of the human transporter, MATE1. Pharmacogenetics and genomics 43 19745787
2016 The Nonmetabolized β-Blocker Nadolol Is a Substrate of OCT1, OCT2, MATE1, MATE2-K, and P-Glycoprotein, but Not of OATP1B1 and OATP1B3. Molecular pharmaceutics 42 26702643
2019 Abundant Expression of OCT2, MATE1, OAT1, OAT3, PEPT2, BCRP, MDR1, and xCT Transporters in Blood-Arachnoid Barrier of Pig and Polarized Localizations at CSF- and Blood-Facing Plasma Membranes. Drug metabolism and disposition: the biological fate of chemicals 36 31771948
2012 Twelve transmembrane helices form the functional core of mammalian MATE1 (multidrug and toxin extruder 1) protein. The Journal of biological chemistry 36 22722930
2016 Associations of genetic polymorphisms of the transporters organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), and ATP-binding cassette subfamily C member 2 (ABCC2) with platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients. Chinese journal of cancer 35 27590272
2012 Synchronized activity of organic cation transporter 3 (Oct3/Slc22a3) and multidrug and toxin extrusion 1 (Mate1/Slc47a1) transporter in transplacental passage of MPP+ in rat. Toxicological sciences : an official journal of the Society of Toxicology 32 22543277
2009 MATE1 has an external COOH terminus, consistent with a 13-helix topology. American journal of physiology. Renal physiology 32 19515813
2020 PPAR-α Deletion Attenuates Cisplatin Nephrotoxicity by Modulating Renal Organic Transporters MATE-1 and OCT-2. International journal of molecular sciences 31 33049997
2018 Expression of MATE1, P-gp, OCTN1 and OCTN2, in epithelial and immune cells in the lung of COPD and healthy individuals. Respiratory research 31 29678179
2013 Transfer of metformin across the rat placenta is mediated by organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein. Reproductive toxicology (Elmsford, N.Y.) 31 23562376
2008 Role of glutamate residues in substrate recognition by human MATE1 polyspecific H+/organic cation exporter. American journal of physiology. Cell physiology 31 18305230
2023 Brief Report: Tyrosine Kinase Inhibitors for Lung Cancers That Inhibit MATE-1 Can Lead to "False" Decreases in Renal Function. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 29 37748692
2016 Inhibition of OCT2, MATE1 and MATE2-K as a possible mechanism of drug interaction between pazopanib and cisplatin. Pharmacological research 28 27178732
2017 Contribution of MATE1 to Renal Secretion of the NMDA Receptor Antagonist Memantine. Molecular pharmaceutics 25 28708400
2017 Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer. European journal of cancer (Oxford, England : 1990) 25 28992563
2010 Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1). The Journal of pharmacology and experimental therapeutics 25 20519552
2018 Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO). Scientific reports 24 29704007
2017 MATE-1 modulation by kinin B1 receptor enhances cisplatin efflux from renal cells. Molecular and cellular biochemistry 22 28161805
2021 In Vitro and In Vivo Inhibition of MATE1 by Tyrosine Kinase Inhibitors. Pharmaceutics 21 34959286
2014 Multidrug and toxic compound extrusion protein-1 (MATE1/SLC47A1) is a novel flavonoid transporter. Journal of agricultural and food chemistry 21 25241911
2016 MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients. Blood cancer journal 20 27635733
2022 Challenges and Opportunities for Improved Drug-Drug Interaction Predictions for Renal OCT2 and MATE1/2-K Transporters. Clinical pharmacology and therapeutics 19 35598119
2019 Changes of drug pharmacokinetics mediated by downregulation of kidney organic cation transporters Mate1 and Oct2 in a rat model of hyperuricemia. PloS one 19 30951542
2020 PPARα-Dependent Modulation by Metformin of the Expression of OCT-2 and MATE-1 in the Kidney of Mice. Molecules (Basel, Switzerland) 16 31963528
2020 A drug-drug interaction study to evaluate the impact of peficitinib on OCT1- and MATE1-mediated transport of metformin in healthy volunteers. European journal of clinical pharmacology 16 32472157
2019 Apical Shear Stress Enhanced Organic Cation Transport in Human OCT2/MATE1-Transfected Madin-Darby Canine Kidney Cells Involves Ciliary Sensing. The Journal of pharmacology and experimental therapeutics 16 30910922
2022 Association of SLC22A1, SLC22A2, SLC47A1, and SLC47A2 Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients. Biomedicines 13 36289808
2021 In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs. International journal of molecular sciences 13 34208557
2019 Interplay of the Organic Cation Transporters OCT1 and OCT2 with the Apically Localized Export Protein MATE1 for the Polarized Transport of Trospium. Molecular pharmaceutics 13 30656943
2018 Lack of effect of the SLC47A1 and SLC47A2 gene polymorphisms on the glycemic response to metformin in type 2 diabetes mellitus patients. Drug metabolism and personalized therapy 13 30433870
2022 Transport Turnover Rates for Human OCT2 and MATE1 Expressed in Chinese Hamster Ovary Cells. International journal of molecular sciences 11 35163393
2017 Pharmacogenetic variation of SLC47A1 gene and metformin response in type2 diabetes patients. Molecular biology research communications 11 28775995
2022 Clinical Aspects of Drug-Drug Interaction and Drug Nephrotoxicity at Renal Organic Cation Transporters 2 (OCT2) and Multidrug and Toxin Exclusion 1, and 2-K (MATE1/MATE2-K). Biological & pharmaceutical bulletin 10 35370262
2020 A Physiologically-Based Pharmacokinetic Model of Trimethoprim for MATE1, OCT1, OCT2, and CYP2C8 Drug-Drug-Gene Interaction Predictions. Pharmaceutics 10 33182761
2018 The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion of asymmetric dimethylarginine via MATE-1 during hepatic ischemia/reperfusion injury. PloS one 10 29346429
2018 Co-administration of nuciferine reduces the concentration of metformin in liver via differential inhibition of hepatic drug transporter OCT1 and MATE1. Biopharmaceutics & drug disposition 10 30294927
2015 Significance of downregulation of renal organic cation transporter (SLC47A1) in cisplatin-induced proximal tubular injury. OncoTargets and therapy 10 26203260
2017 Relationship between DNA Methylation in the 5' CpG Island of the SLC47A1 (Multidrug and Toxin Extrusion Protein MATE1) Gene and Interindividual Variability in MATE1 Expression in the Human Liver. Molecular pharmacology 8 29070695
2024 Identification and characterization of an endogenous biomarker of the renal vectorial transport (OCT2-MATE1). Biopharmaceutics & drug disposition 7 38305087
2022 Impact of Sotorasib on the Pharmacokinetics and Pharmacodynamics of Metformin, a MATE1/2K Substrate, in Healthy Subjects. Clinical pharmacokinetics 7 36529835
2021 Evaluation of the potential drug interactions mediated through P-gp, OCT2, and MATE1/2K with filgotinib in healthy subjects. Clinical and translational science 7 34498807
2018 Fampridine is a Substrate and Inhibitor of Human OCT2, but not of Human MATE1, or MATE2K. Pharmaceutical research 7 29915999
2023 Platinum-Acridine Agents with High Activity in Cancers Expressing the Solute Carrier MATE1 (SLC47A1). ACS medicinal chemistry letters 6 37583829
2023 Targeting the multidrug and toxin extrusion 1 gene (SLC47A1) sensitizes glioma stem cells to temozolomide. American journal of cancer research 6 37818053
2017 Differential increments of basal glucagon-like-1 peptide concentration among SLC47A1 rs2289669 genotypes were associated with inter-individual variability in glycaemic response to metformin in Chinese people with newly diagnosed Type 2 diabetes. Diabetic medicine : a journal of the British Diabetic Association 6 28321905
2015 The multidrug transporter MATE1 sequesters OCs within an intracellular compartment that has no influence on OC secretion in renal proximal tubules. American journal of physiology. Renal physiology 6 26538438
2013 Identification and functional characterization of novel MATE1 genetic variations in Koreans. Biochemical and biophysical research communications 6 23558289
2023 Thioacetamide-Induced Acute Liver Injury Increases Metformin Plasma Exposure by Downregulating Renal OCT2 and MATE1 Expression and Function. Biomedicines 5 38137535
2023 Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes. Research in pharmaceutical sciences 5 39005567
2022 The influence of metformin transporter gene SLC22A1 and SLC47A1 variants on steady-state pharmacokinetics and glycemic response. PloS one 5 35905099
2022 Mirogabalin, a novel α2δ ligand, is not a substrate of LAT1, but of PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1 and MATE2-K. Xenobiotica; the fate of foreign compounds in biological systems 5 36170033
2019 Relationship of MATE1 Inhibition and Cytotoxicity in Nephrotoxicity: Application for Safety Evaluation in Early Drug Discovery. Toxicological sciences : an official journal of the Society of Toxicology 5 31020312
2015 [Establishment of MDCK cell models expressing human MATE1 or co-expressing with human OCT1 or OCT2]. Yao xue xue bao = Acta pharmaceutica Sinica 5 26552145
2024 DkDTX1/MATE1 mediates the accumulation of proanthocyanidin and affects astringency in persimmon. Plant, cell & environment 4 39169830
2023 MATE1 expression in the cochlea and its potential involvement in cisplatin cellular uptake and ototoxicity. Acta oto-laryngologica 4 36943799
2021 The L125F MATE1 variant enriched in populations of Amerindian origin is associated with increased plasma levels of metformin and lactate. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 4 34388523
2025 Structural basis of drug recognition by human MATE1 transporter. Nature communications 3 41145429
2024 A Drug-Drug Interaction Study to Evaluate the Impact of Rimegepant on OCT2- and MATE1-Mediated Transport of Metformin in Healthy Participants. Clinical pharmacology in drug development 3 38174905
2023 The association study between changes in HbA1C with rs2250486 and rs67238751 genetic variants for SLC47A1 in newly diagnosed Iranian patients with type 2 diabetes mellitus: 6 months follow-up study. Endocrinology, diabetes & metabolism 3 36786075
2022 Association of the SLC47A1 Gene Variant With Responses to Metformin Monotherapy in Drug-naive Patients With Type 2 Diabetes. The Journal of clinical endocrinology and metabolism 3 35639991
2018 Indinavir Alters the Pharmacokinetics of Lamivudine Partially via Inhibition of Multidrug and Toxin Extrusion Protein 1 (MATE1). Pharmaceutical research 3 29302757
2018 Purification and reconstitution of polyspecific H+/organic cation antiporter human MATE1. Biochimica et biophysica acta. Biomembranes 3 30028956
2017 Genetic polymorphisms of multidrug and toxin extrusion proteins (MATE1 and MATE2) in South Indian population. BioImpacts : BI 3 28546950
2024 The OCT2/MATE1 Interaction Between Trifluridine, Metformin and Cimetidine: A Crossover Pharmacokinetic Study. Clinical pharmacokinetics 2 38951433
2024 Prediction of Inhibitory Activity against the MATE1 Transporter via Combined Fingerprint- and Physics-Based Machine Learning Models. Journal of chemical information and modeling 2 39254593
2019 Involvement of Renal Efflux Transporter MATE1 in Renal Excretion of Flecainide. Biological & pharmaceutical bulletin 2 31257298
2016 Quercetin intake, MATE1 polymorphism, and metabolic syndrome in Korean population: Hallym aging study. Food science and biotechnology 2 30263475
2025 Bupropion decreases plasma levels of asymmetric dimethylarginine and ameliorates renal injury by modulation of Ddah1, Oatp4c1, Oct2, and Mate1 in rats with adenine-induced chronic renal injury. Frontiers in pharmacology 1 40474975
2025 Rat-Specific Expression of Placental MATE1 Contributes to Species Difference in Fetal Transfer of Metformin and 1-Methyl-4-Phenylpyridinium. Molecular pharmaceutics 1 41184726
2022 Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression. Human molecular genetics 1 34505146
2025 Frequency of Polymorphisms in SLC47A1 (rs2252281 and rs2289669) and SLC47A2 (rs34834489 and rs12943590) and the Influence of SLC22A1 (rs72552763 and rs622342) on HbA1c Levels in Mexican-Mestizo Patients with DMT2 Treated with Metformin Monotherapy. International journal of molecular sciences 0 40943569
2016 Lack of genomic diversity in the SLC47A1 gene within the indigenous Xhosa population. Drug metabolism and personalized therapy 0 27226103

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