Affinage

SLC7A5

Large neutral amino acids transporter small subunit 1 · UniProt Q01650

Length
507 aa
Mass
55.0 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC7A5 (LAT1) is the catalytic light chain of a heterodimeric large-neutral-amino-acid transporter that couples nutrient import to anabolic signaling across muscle, neurons, immune cells, epithelia, and tumors (PMID:9837878, PMID:24586861). It associates with the CD98/4F2hc glycoprotein (SLC3A2) through a conserved disulfide bond; reconstitution of recombinant LAT1 in proteoliposomes shows it functions as a Na⁺- and pH-independent antiporter (histidine is a preferred substrate), with CD98 dispensable for transport itself but required for plasma-membrane routing (PMID:29988369). Substrate recognition and regulation map to discrete residues defined by mutagenesis: F252/S342/C335 form the substrate site, C407 is the attachment point for covalent dithiazole/dithiazine inhibitors, and K204 mediates ATP modulation, while cholesterol raises transport Vmax and ATP acts synergistically to stabilize an inward-open state (PMID:28088504, PMID:28709952, PMID:28272458, PMID:33028978). Surface levels are controlled post-translationally by PKC/Nedd4-2–dependent ubiquitylation of N-terminal lysines K19/K25/K30, driving endocytosis and degradation (PMID:31728037). Functionally, leucine and other LNAA influx through SLC7A5 activates mTORC1 to drive protein synthesis, differentiation, and proliferation—demonstrated in skeletal muscle, cerebellar neurons, intestinal secretory cells, B and T lymphocytes, monocytes/macrophages, and KRAS-mutant tumors—with loss of SLC7A5 triggering the integrated stress response and developmental defects in vivo (PMID:31789450, PMID:24586861, PMID:33414552, PMID:32821949, PMID:29422900, PMID:38617535). Beyond canonical LNAA antiport, SLC7A5 transports pharmacological cargo (gabapentin, pregabalin), citrulline under arginine limitation, and copper-histidinate via an unconventional uniport mechanism, and supports tryptophan-driven NAD⁺ synthesis and glutathione-dependent stress defense (PMID:23567998, PMID:30374619, PMID:37692288, PMID:39756034, PMID:40611146, PMID:33567754). Transcriptionally it integrates oncogenic and stress inputs including HIF-2α, Wnt/β-catenin, c-Myc/SRC2, MITF, and YAP/TAZ, and is repressed by glucocorticoid-receptor transrepression (PMID:23103253, PMID:31789450, PMID:26094588, PMID:30761250, PMID:37094160, PMID:32240722, PMID:39704172). Independent of transport, SLC7A5 physically associates with and suppresses voltage-gated potassium channels Kv1.1 and Kv1.2, dramatically shifting their gating (PMID:30356053, PMID:33164746).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Establishing that the CD98 light chain is the SLC7A5/E16 protein answered what gives the CD98 antigen its amino-acid-transport activity, unifying an immunology antigen with a transporter.

    Evidence MS peptide sequencing, reciprocal co-IP, and reconstitution of HA-tagged E16 with CD98 heavy chain

    PMID:10072483 PMID:9837878

    Open questions at the time
    • Did not define transport mechanism or substrate selectivity
    • Did not establish whether CD98 is required for activity versus trafficking
  2. 2018 High

    Reconstitution of recombinant LAT1 in proteoliposomes settled the transport mode—Na⁺/pH-independent antiport with CD98 needed only for membrane routing, not catalysis.

    Evidence Proteoliposome radiolabeled transport assays with recombinant human LAT1 and site-directed mutagenesis

    PMID:29988369

    Open questions at the time
    • Did not resolve full physiological substrate hierarchy in cells
    • Structural basis of antiport conformational cycle not defined
  3. 2017 High

    Mutagenesis pinpointed the substrate-binding residues and a druggable cysteine, converting a black-box carrier into a defined pharmacological target.

    Evidence Proteoliposome transport with F252/S342/C335/C407 mutants, chemical modification, and C407A covalent-inhibitor rescue

    PMID:28088504 PMID:28709952

    Open questions at the time
    • No high-resolution structure of inhibitor-bound transporter in these studies
    • Selectivity of covalent inhibitors across SLC7 family not established
  4. 2017 High

    Identifying cholesterol and ATP as positive modulators (Vmax increase; K204-dependent ATP synergy) revealed that LAT1 activity is tuned by membrane and energetic state, not just substrate supply.

    Evidence Cholesterol-depletion uptake assays, purification with cholesterol analogue, and K204Q mutagenesis with docking

    PMID:28272458 PMID:33028978

    Open questions at the time
    • Physiological relevance of ATP modulation in intact cells untested
    • How cholesterol stabilizes the conformational state structurally unknown
  5. 2019 High

    Mapping PKC/Nedd4-2–dependent ubiquitylation of K19/K25/K30 explained how surface LAT1 levels are acutely downregulated, linking signaling to transporter turnover.

    Evidence Endocytosis and ubiquitylation assays, Nedd4-2 siRNA, and systematic lysine mutagenesis in HeLa

    PMID:31728037

    Open questions at the time
    • Physiological triggers of Nedd4-2 recruitment beyond PMA not defined
    • Whether other E3 ligases regulate LAT1 in vivo unaddressed
  6. 2014 High

    Tissue-specific knockouts established that SLC7A5 is genuinely required for LNAA-driven mTOR-S6K signaling rather than redundant, first shown in skeletal muscle.

    Evidence MCK-Cre conditional knockout with leucine challenge and S6K Thr389 phospho-readout in vivo

    PMID:24586861

    Open questions at the time
    • Did not address non-muscle tissues
    • Contribution relative to other LNAA transporters not quantified
  7. 2018 High

    CRISPR knockout of ASCT2 versus LAT1 directly tested and refuted the proposed ASCT2→LAT1 exchange-coupling model for mTORC1 activation, sharpening the mechanistic picture.

    Evidence CRISPR-Cas9 knockout of ASCT2 or LAT1 with uptake, mTORC1, and GCN2 pathway readouts in cancer lines

    PMID:29326164

    Open questions at the time
    • Did not identify the antiport counter-substrate sustaining LAT1 import in cells
    • Tested in limited cell contexts
  8. 2020 High

    In vivo knockdown with Rheb rescue across neuronal, embryonic, intestinal, and tumor systems placed SLC7A5 firmly upstream of mTORC1 in development and disease.

    Evidence Conditional knockouts/electroporation knockdown with phospho-mTOR readouts, integrated stress response, and constitutively active Rheb rescue

    PMID:31789450 PMID:32821949 PMID:33414552 PMID:38617535

    Open questions at the time
    • Whether SLC7A5 signals to mTORC1 solely via leucine sensing (Sestrin2) not resolved here
    • Tissue-specific downstream effectors differ and are incompletely mapped
  9. 2018 Medium

    Demonstrating leucine-influx–dependent mTORC1 activation in monocytes, B cells, and T cells extended SLC7A5 from anabolic support to control of immune effector programs and glycolytic reprogramming.

    Evidence siRNA/pharmacological inhibition with ECAR, cytokine, plasmablast, and proliferation readouts; SRC2/c-Myc rescue in CD4⁺ T cells

    PMID:29422900 PMID:30092695 PMID:37094160

    Open questions at the time
    • Quantitative contribution of LAT1 versus other transporters to immune metabolism unclear
    • Several findings rest on single-lab functional inhibition
  10. 2018 High

    An unbiased interactome screen plus electrophysiology revealed a transport-independent role: SLC7A5 binds and profoundly suppresses Kv1.1/Kv1.2 channel gating, connecting it to neuronal excitability and channelopathy.

    Evidence MS interactome, heterologous co-expression, chimeric-channel and whole-cell patch clamp, disease-mutation validation

    PMID:30356053 PMID:32311044 PMID:33164746

    Open questions at the time
    • Structural basis of the SLC7A5–Kv interaction unresolved
    • Physiological significance in native neurons not fully established
  11. 2023 High

    Substrate-expansion studies showed LAT1 carries drugs and non-canonical cargo (gabapentin, pregabalin, citrulline, copper-histidinate via uniport), redefining its physiological and pharmacological scope.

    Evidence Kinetic uptake in cell lines, isotope tracing, proteoliposome transport, MS, and crystallography of the Cu(His)₂ complex

    PMID:23567998 PMID:27 PMID:30374619 PMID:37692288 PMID:39756034

    Open questions at the time
    • Quantitative in vivo contribution of unconventional uniport unknown
    • Whether other metal-amino-acid complexes are physiological substrates untested
  12. 2024 Medium

    Transcriptional and post-transcriptional regulators (HIF-2α, Wnt/β-catenin, c-Myc/SRC2, MITF, YAP/TAZ, GR, IGF2BP2/m6A, ALYREF, TRIM35) were mapped, showing SLC7A5 as a convergent node downstream of oncogenic, hypoxic, and hormonal signaling.

    Evidence ChIP/ChIP-seq, reporter assays, RIP/MeRIP, ubiquitination assays, and knockdown/rescue across multiple cell systems

    PMID:23103253 PMID:26094588 PMID:30761250 PMID:31618 PMID:32240722 PMID:37094160 PMID:38281999 PMID:38402198 PMID:39304904 PMID:39704172

    Open questions at the time
    • Most regulatory axes shown in single labs/contexts
    • Hierarchy and crosstalk among these inputs not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the transport-dependent mTORC1 role and the transport-independent Kv channel modulation are integrated within a single cell, and the in vivo physiological weight of unconventional substrates, remain open.
  • No structure capturing both substrate transport and Kv binding
  • Counter-substrate sustaining cellular antiport import unidentified
  • Relative physiological importance of LNAA versus drug/metal/citrulline transport unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0098772 molecular function regulator activity 3 GO:0140104 molecular carrier activity 3
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-382551 Transport of small molecules 5 R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-112316 Neuronal System 2
Partners
IGF2BP2KCNA1KCNA2NEDD4LSLC3A2TRIM35
Complex memberships
LAT1/CD98 (SLC7A5–SLC3A2) heterodimeric amino acid transporter

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 The CD98 light chain is identical to the TA1/E16 protein (SLC7A5), established by partial amino acid sequence identity from mass spectrometry, antibody cross-reactivity, and co-immunoprecipitation of hemagglutinin-tagged E16/SLC7A5 with anti-CD98 heavy chain antibody. Mass spectrometry peptide sequencing, co-immunoprecipitation, immunoblotting, genetic reconstitution The Journal of biological chemistry High 9837878
1999 CD98 light chain (SLC7A5/LAT1) is almost identical to the amino acid transporter E16; the gene maps to human chromosome 16q24. The CD98LC/SLC7A5 protein was co-purified with the CD98 heavy chain from HeLa cells. Affinity purification, N-terminal protein sequencing, cDNA cloning, FISH Journal of immunology Medium 10072483
2018 SLC7A5 (LAT1) forms a heterodimeric amino acid transporter with the glycoprotein CD98 (SLC3A2) through a conserved disulfide bond; in proteoliposomes reconstituted with recombinant human LAT1, transport is Na⁺- and pH-independent antiport; the preferred substrate is histidine; CD98 is not required for transport activity and is instead involved in routing LAT1 to the plasma membrane. Proteoliposome reconstitution with recombinant protein, radiolabeled transport assay, site-directed mutagenesis Frontiers in chemistry High 29988369
2017 Residues F252, S342, and C335 are crucial for substrate recognition in LAT1 (SLC7A5); C407 plays a minor role. The transporter preferentially adopts a dimeric structure and catalyzes antiport following a simultaneous random mechanism. K⁺ has regulatory properties on LAT1 similar to LeuT. Site-directed mutagenesis, chemical modification, transport assay in proteoliposomes, bioinformatics Biochimica et biophysica acta. General subjects High 28088504
2017 Cysteine residue C407 in the substrate binding site of LAT1 (SLC7A5) forms a covalent disulfide bond with dithiazole/dithiazine inhibitors, confirmed by loss of inhibition in the C407A mutant and reversal of inhibition by dithioerythritol. These covalent inhibitors show IC50 <1 µM and cause cell death in SLC7A5-expressing cancer cells. Proteoliposome transport assay, site-directed mutagenesis (C407A), molecular docking, cell viability assay Biochemical pharmacology High 28709952
2017 Cholesterol depletion reduces the Vmax but not the Km of LAT1-mediated transport, indicating cholesterol modulates transporter activity by stabilizing a specific conformational state. A soluble cholesterol analogue was required for stable purification of the LAT1/CD98 complex with retained substrate-binding activity. Cellular uptake assay with cholesterol depletion, protein purification with cholesterol analogue, substrate binding assay Scientific reports Medium 28272458
2020 ATP synergistically stimulates LAT1 (SLC7A5) transport activity in the presence of cholesterol, selectively increasing substrate affinity at the internal site (suggesting stabilization of inward-open conformation). Computational docking and site-directed mutagenesis identified Lys204 as the ATP interaction residue; the K204Q mutant showed impaired function and abolished ATP response. Proteoliposome transport assay, computational docking, site-directed mutagenesis (K204Q) Scientific reports High 33028978
2019 PKC activation by PMA triggers efficient endocytosis and degradation of LAT1 (SLC7A5) in HeLa cells, mediated by Nedd4-2 ubiquitin ligase. Systematic mutagenesis identified three lysines (K19, K25, K30) in the N-terminal cytosolic tail as required for PMA-induced ubiquitylation and downregulation. Endocytosis assay, ubiquitylation assay, Nedd4-2 siRNA knockdown, systematic lysine mutagenesis Scientific reports High 31728037
2012 HIF2α activates mTORC1 by transcriptionally upregulating SLC7A5 expression; HIF2α binds directly to the Slc7a5 proximal promoter. This pathway links oxygen sensing to mTORC1 activation and accounts for tumor-promoting properties of HIF2α in VHL-deficient cells. Reporter assay, chromatin immunoprecipitation (ChIP), genetic overexpression/knockdown, mTORC1 activity assay Molecular cell High 23103253
2019 Wnt/β-catenin signaling directly supports Slc7a5 expression; loss of Wnt/β-catenin inhibits Slc7a5 and induces the integrated stress response (aberrant mTORC1 activity, increased apoptosis). Slc7a5-null mouse embryos display profound neural and limb bud outgrowth defects accompanied by induction of the integrated stress response. Slc7a5-null mouse embryo analysis, transcriptomics, phosphoprotein analysis, apoptosis assay, genetic epistasis with Wnt pathway mutants EMBO reports High 31789450
2014 Muscle-specific knockout of Slc7a5 blunts leucine-induced mTOR-S6K (Thr389) phosphorylation in skeletal muscle in vivo, and reduces intramuscular leucine/isoleucine concentrations and S6K activity on low-protein diets, demonstrating that SLC7A5 is required for LNAA-dependent mTOR-S6K pathway activation in skeletal muscle. Conditional Cre-lox knockout (MCK-Cre), intraperitoneal leucine injection, phosphoprotein analysis (S6K Thr389), amino acid measurement PloS one High 24586861
2021 SLC7A5 is critical for KRAS-mutant colorectal cancer growth; mechanistically it maintains intracellular amino acid levels after KRAS activation to support increased bulk protein synthesis. Combined deletion of Slc7a5 and mTORC1 inhibition abrogates established Kras-mutant tumor growth. Conditional mouse knockout, metabolic tracing, protein synthesis assay, tumor growth assay, genetic epistasis with mTORC1 pathway Nature genetics High 33414552
2020 Slc7a5 knockdown in cerebellar granule cell precursors reduces mTOR pathway activity and impairs late-phase granule cell dendrite maturation and survival; these defects are rescued by constitutively active Rheb (an mTOR activator), placing SLC7A5 upstream of mTOR in neuronal development. In vivo electroporation-based knockdown, mTOR pathway phosphorylation assay, morphological analysis, genetic rescue with Rheb Human molecular genetics High 32821949
2018 SLC7A5-mediated leucine influx activates mTORC1 and drives pro-inflammatory cytokine (IL-1β) production and glycolytic reprogramming in activated human monocytes/macrophages; pharmacological blockade or silencing of SLC7A5 reduces mTORC1 activity, glycolysis (measured as ECAR), and IL-1β production. siRNA knockdown, pharmacological inhibition, mTORC1 activity assay, metabolic flux (ECAR), cytokine measurement Frontiers in immunology Medium 29422900
2018 Slc7a5 co-expression with Kv1.2 dramatically hyperpolarizes the voltage-dependence of Kv1.2 activation by ~47 mV, reduces total Kv1.2 protein, and accelerates inactivation; these effects are attenuated by co-expression of Slc3a2. Disease-linked Slc7a5 mutations show a localization defect and attenuated effects on Kv1.2. Epilepsy-linked gain-of-function Kv1.2 mutants show enhanced sensitivity to Slc7a5. Mass spectrometry interactome screen, co-expression in heterologous system, whole-cell electrophysiology, Western blot, immunofluorescence Nature communications High 30356053
2020 Slc7a5 regulates Kv1.1 channels by inhibiting channel activity; this inhibition can be reversed by supraphysiological hyperpolarization. Exchange of the voltage-sensing domain between Kv1.1 and Kv1.2 controls Slc7a5 sensitivity, and a specific position in the S1 segment is a major determinant of Slc7a5 modulation. Knockdown of endogenous Slc7a5, chimeric channel electrophysiology, heterologous expression, whole-cell patch clamp eLife High 33164746
2020 Slc7a5-mediated current suppression of Kv1.2 is attenuated when Kvβ1.2 is co-expressed; however, gating shifts and modified inactivation properties from both Slc7a5 and Kvβ are additive, demonstrating convergent but independent regulation of Kv1.2 by the two accessory proteins. Co-expression in heterologous system, whole-cell electrophysiology, Western blot The Journal of general physiology Medium 32311044
2013 Gabapentin is a substrate of LAT1 (SLC7A5); Km values of 530 µM (in brain endothelial cells) and 217 µM (in LAT1-transfected HEK293 cells) were determined by kinetic analysis. LAT1-mediated transport was 3–10-fold higher than other transport processes at physiological concentrations. Radiolabeled uptake assay, siRNA knockdown, LAT1 overexpression in HEK293 cells, Michaelis-Menten kinetics, mathematical modelling Biochemical pharmacology High 23567998
2018 LAT1 (SLC7A5) transports pregabalin; overexpression of LAT1 but not LAT2 in HEK293 cells increases pregabalin uptake with Km of 0.288 mM. LAT1 siRNA knockdown in hCMEC/D3 cells reduces pregabalin uptake by 75%. Transporter overexpression in HEK293, LC-MS/MS uptake assay, siRNA knockdown, competitive inhibition assay Pharmaceutical research High 30374619
2016 Dexamethasone downregulates SLC7A5 expression via glucocorticoid receptor (GR)-mediated transrepression; GR binds the proximal promoter of SLC7A5. The resulting reduction in amino acid uptake inhibits mTOR signaling, causing G1/S cell cycle arrest, enhanced autophagy and apoptosis in BeWo placental cells. The GR antagonist RU486 abolishes these effects. ChIP, reporter assay (GR nuclear translocation), siRNA knockdown of SLC7A5, mTOR pathway analysis, cell cycle analysis, GR antagonist treatment Journal of cellular physiology High 26094588
2019 Hypoxia upregulates Slc7a5 expression in differentiated neuronal cells through HIF-2α, which binds directly to the proximal promoter of Slc7a5. shRNA knockdown of HIF-2α (but not HIF-1α) markedly reduces hypoxia-induced Slc7a5 upregulation. ChIP, shRNA knockdown of HIF-2α and HIF-1α, qRT-PCR FEBS open bio Medium 30761250
2014 Insulin (0.5 nmol/L) increases SLC7A5/LAT1 mRNA abundance in C2C12 myotubes via an mTORC1-dependent mechanism; both low and high doses of rapamycin prevent this induction, placing SLC7A5 regulation downstream of mTORC1. mTORC1 inhibition with rapamycin, phosphoprotein analysis (S6K1, S6), mRNA quantification (qRT-PCR) Physiological reports Medium 24760501
2011 miR-126 directly targets SLC7A5; siRNA-mediated suppression of SLC7A5 phenocopies miR-126 overexpression (G1 delay, proliferation inhibition) in H69 small cell lung cancer cells. miRNA overexpression, siRNA knockdown, cell cycle analysis, proliferation assay FEBS letters Medium 21439283
2018 ASCT2 (SLC1A5) knockout significantly reduces glutamine import but does not affect leucine uptake via LAT1, and does not alter mTORC1 activity or the GCN2/EIF2a/ATF4 amino acid stress response, contrary to the proposed functional coupling model of ASCT2 feeding LAT1-mediated mTORC1 activation. CRISPR-Cas9 knockout of ASCT2 or LAT1, amino acid uptake assay, mTORC1 activity assay (S6K1/S6), GCN2 pathway analysis, tumor growth assay The Journal of biological chemistry High 29326164
2023 SRC2 (steroid nuclear receptor coactivator 2) co-activates c-Myc to stimulate Slc7a5 expression in CD4⁺ T cells; SRC2-deficient T cells fail to upregulate Slc7a5, and forced expression of Slc7a5 rescues proliferation, cytokine production, and the ability to induce EAE. Conditional T cell-specific knockout, forced gene expression rescue, in vitro and in vivo functional assays (proliferation, cytokine production), adoptive transfer Proceedings of the National Academy of Sciences High 37094160
2018 l-Leucine influx through Slc7a5 is required for mTORC1 activation, plasmablast differentiation, and production of IgG and inflammatory cytokines in CpG-stimulated human B cells. CpG stimulation induces Slc7a5 expression and leucine uptake; Slc7a5 inhibition abrogates these responses. RT-PCR, flow cytometry, radioisotope uptake assay, pharmacological inhibition, mTORC1 activity assay Modern rheumatology Medium 30092695
2024 TRIM35 E3 ubiquitin ligase interacts with, ubiquitinates, and upregulates the amino acid transporter SLC7A5 in cardiac fibroblasts, enhancing amino acid transport and mTORC1 activation. Overexpression of SLC7A5 reverses the reduced cardiac fibrosis caused by TRIM35 conditional knockout. LC-MS/MS, co-immunoprecipitation, ubiquitination assay, conditional knockout in mice, SLC7A5 rescue overexpression, mTORC1 activity assay Cell communication and signaling Medium 39304904
2023 LAT1 (SLC7A5) transports copper(II)-histidinate [Cu(His)₂] via an unconventional uniport mechanism, distinct from its canonical antiport of amino acids. Site-directed mutagenesis, radiolabeled transport assays, mass spectrometry, and crystal structure of the Cu(His)₂ complex confirmed transport and identified the binding interaction. Bioinformatics, site-directed mutagenesis, radiolabeled transport assay, mass spectrometry, crystallography of substrate complex iScience High 37692288
2022 SLC7A5 (LAT1) is required for normal secretory cell differentiation in mouse intestinal epithelium; intestinal epithelial cell-specific knockout reduces mTORC1 signaling, causes dedifferentiation of Paneth cells (with loss of secretory granules), and alters goblet cell distribution, resulting in indirect increases in crypt cell proliferation. IEC-specific conditional knockout (Slc7a5ΔIEC), scRNA-seq, electron microscopy, mTORC1 pathway analysis International journal of biological sciences High 38617535
2025 SLC7A5 functions as a citrulline transporter under arginine-limited conditions; isotope tracing shows citrulline uptake and conversion to arginine are dependent on SLC7A5 expression. Loss of SLC7A5 reduces tumor growth and citrulline import in a mouse tumor model. CRISPR-Cas9 functional screen, isotope tracing (citrulline metabolism), pharmacological inhibition, mouse tumor model Cell reports High 39756034
2025 LAT1 (SLC7A5) promotes TNBC progression and chemoresistance by facilitating L-tryptophan uptake and upregulating QPRT (rate-limiting enzyme in de novo NAD⁺ synthesis), increasing the cytosolic NAD⁺/NADH ratio, which enhances phosphorylation of PKM2 and LDHA to amplify glycolysis. LAT1 knockdown and pharmacological inhibition, steady-state polar metabolite profiling (LC-MS), pyruvate/lactate assay, Seahorse metabolic assay, in vivo orthotopic and PDX mouse models Journal of experimental & clinical cancer research Medium 40611146
2024 IGF2BP2 enhances SLC7A5 mRNA stability and translation through m6A modification; SLC7A5-mediated methionine transport supports S-adenosylmethionine production, which increases H3K4me3 at the IGF2BP2 promoter to form a positive feedback loop. FBW7/GSK3β ubiquitinate and degrade IGF2BP2 to break this loop. ChIP-qPCR, RIP, MeRIP-qPCR, RNA pull-down, co-immunoprecipitation, ubiquitination assay Journal of experimental & clinical cancer research Medium 38281999
2015 Diesel exhaust particle extract induces LAT1 (SLC7A5)/CD98hc expression and LAT1-mediated leucine transport in bronchial epithelial cells via the aryl hydrocarbon receptor (AhR) pathway; AhR antagonist or AhR siRNA prevents this induction. CD98hc induction subsequently activates the integrin/FAK/ERK signaling pathway, upregulating MMP-2. Chemical AhR antagonist, siRNA knockdown of AhR, mRNA and protein expression analysis, leucine accumulation assay, MMP-2 activity assay Toxicology and applied pharmacology Medium 26621329
2022 SLC7A5 (LAT1) mediates methylmercury-L-cysteine conjugate uptake in placental cells; LAT1-depleted HTR-8/SVneo cells accumulate less MeHg but are more susceptible to MeHg toxicity due to lower glutathione (GSH) levels, demonstrating that LAT1-mediated amino acid transport is essential for de novo GSH synthesis and oxidative stress defense. siRNA knockdown of LAT1, MeHg uptake measurement, cell viability, apoptosis, oxidative stress assays, GSH measurement International journal of molecular sciences Medium 33567754
2022 SLC7A5 (LAT1) is required for normal myoblast viability, differentiation, and fusion; pharmacological inhibition and genetic knockdown both impair these processes. LAT1 expression decreases during myotube differentiation and is reduced under atrophic conditions in vitro. Pharmacological inhibition, genetic knockdown (siRNA), myogenesis assays (viability, differentiation, fusion), Western blot American journal of physiology. Cell physiology Medium 35848618
2022 Intrathecal administration of the LAT1 (SLC7A5) inhibitor JPH203 alleviates allodynia in the spared nerve injury mouse model of neuropathic pain. JPH203 treatment reduces excitability of small-diameter DRG neurons from SNI mice and affects tetrodotoxin-resistant sodium currents in naive rat DRG neurons. Intrathecal drug administration, behavioral assay (allodynia), whole-cell electrophysiology (current-clamp and voltage-clamp), Western blot, immunohistochemistry Pflugers Archiv : European journal of physiology Medium 35048187
2020 MITF directly transcriptionally targets SLC7A5; SLC7A5 inhibition or knockdown decreases melanin synthesis in melanocytes and melanoma cells without affecting tyrosinase activity, and acts through a different pathway from kojic acid (a tyrosinase inhibitor), revealing SLC7A5 as a regulator of melanogenesis. ChIP-seq, microarray, siRNA knockdown, pharmacological inhibition (BCH, JPH203), melanin measurement, tyrosinase activity assay, reconstructed human epidermis model The Journal of investigative dermatology Medium 32240722
2024 ALYREF (m5C reader) binds and stabilizes JunD mRNA via m5C modification; JunD then transcriptionally upregulates SLC7A5, increasing LNAA transport and mTORC1 activation while depleting amino acids in the tumor microenvironment to restrict CD8⁺ T cell function. m5C RNA-IP, RIP, mRNA stability assay, ChIP, SLC7A5 expression analysis, CD8⁺ T cell functional assay, in vivo tumor model Cell death discovery Medium 38402198
2024 YAP/TAZ reverses KRAS inhibitor-induced proliferation arrest by activating the SLC7A5/mTORC1 axis; knockdown of YAP/TAZ or TEADs reduces SLC7A5-dependent mTORC1 activity and sensitizes resistant cells to KRAS G12C inhibitors. Transcriptomic analysis, genetic knockdown (YAP/TAZ/TEAD siRNA), SLC7A5 expression analysis, mTORC1 pathway assay, drug sensitivity assay JCI insight Medium 39704172
2022 Alliin (a garlic-derived nutraceutical) is a substrate of LAT1 (SLC7A5), as demonstrated by competitive inhibition and direct transport in proteoliposomes reconstituted with recombinant human LAT1. Computational docking predicted interaction with the substrate binding site, confirmed by functional assay. Bioinformatics/docking, proteoliposome transport assay with recombinant protein Frontiers in pharmacology Medium 35401172

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 The Human SLC7A5 (LAT1): The Intriguing Histidine/Large Neutral Amino Acid Transporter and Its Relevance to Human Health. Frontiers in chemistry 231 29988369
2021 The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nature genetics 208 33414552
2021 Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics. Pharmacology & therapeutics 199 34390745
2012 HIF2α acts as an mTORC1 activator through the amino acid carrier SLC7A5. Molecular cell 174 23103253
2018 The glutamine transporter ASCT2 (SLC1A5) promotes tumor growth independently of the amino acid transporter LAT1 (SLC7A5). The Journal of biological chemistry 147 29326164
2021 Targeting SLC1A5 and SLC3A2/SLC7A5 as a Potential Strategy to Strengthen Anti-Tumor Immunity in the Tumor Microenvironment. Frontiers in immunology 135 33953707
2011 miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5. FEBS letters 116 21439283
2018 Role of SLC7A5 in Metabolic Reprogramming of Human Monocyte/Macrophage Immune Responses. Frontiers in immunology 110 29422900
2013 Transport of gabapentin by LAT1 (SLC7A5). Biochemical pharmacology 110 23567998
2014 The catalytic subunit of the system L1 amino acid transporter (slc7a5) facilitates nutrient signalling in mouse skeletal muscle. PloS one 94 24586861
1996 Expression of a highly conserved oncofetal gene, TA1/E16, in human colon carcinoma and other primary cancers: homology to Schistosoma mansoni amino acid permease and Caenorhabditis elegans gene products. Cancer research 81 8895758
2022 CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex. Journal of experimental & clinical cancer research : CR 77 35986300
2017 Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol. Scientific reports 67 28272458
2009 Abnormal expression of myelination genes and alterations in white matter fractional anisotropy following prenatal viral influenza infection at E16 in mice. Schizophrenia research 66 19487109
1998 The light chain of CD98 is identified as E16/TA1 protein. The Journal of biological chemistry 66 9837878
2017 Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs. Biochemical pharmacology 61 28709952
2017 Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer. Biochemical and biophysical research communications 58 29277611
2017 Novel insights into the transport mechanism of the human amino acid transporter LAT1 (SLC7A5). Probing critical residues for substrate translocation. Biochimica et biophysica acta. General subjects 55 28088504
1997 Differential dissection of the rat E16 ventral mesencephalon and survival and reinnervation of the 6-OHDA-lesioned striatum by a subset of aldehyde dehydrogenase-positive TH neurons. Cell transplantation 44 9171157
2018 Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line. Pharmaceutical research 42 30374619
2022 Hypoxia increases expression of selected blood-brain barrier transporters GLUT-1, P-gp, SLC7A5 and TFRC, while maintaining barrier integrity, in brain capillary endothelial monolayers. Fluids and barriers of the CNS 41 34983574
2016 Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells. Journal of cellular physiology 38 26094588
2020 Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer. International journal of molecular sciences 37 32093034
2023 Targeting glutamine metabolic reprogramming of SLC7A5 enhances the efficacy of anti-PD-1 in triple-negative breast cancer. Frontiers in immunology 36 37731509
2022 The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications. Basic & clinical pharmacology & toxicology 34 36460306
2020 The amino acid transporter Slc7a5 regulates the mTOR pathway and is required for granule cell development. Human molecular genetics 33 32821949
2019 Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos. EMBO reports 33 31789450
2018 Slc7a5 regulates Kv1.2 channels and modifies functional outcomes of epilepsy-linked channel mutations. Nature communications 31 30356053
2024 FBW7/GSK3β mediated degradation of IGF2BP2 inhibits IGF2BP2-SLC7A5 positive feedback loop and radioresistance in lung cancer. Journal of experimental & clinical cancer research : CR 29 38281999
2020 ATP modulates SLC7A5 (LAT1) synergistically with cholesterol. Scientific reports 28 33028978
2014 Insulin increases mRNA abundance of the amino acid transporter SLC7A5/LAT1 via an mTORC1-dependent mechanism in skeletal muscle cells. Physiological reports 28 24760501
2024 ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion. Cell death discovery 25 38402198
2023 The proliferation of human mucosal-associated invariant T cells requires a MYC-SLC7A5-glycolysis metabolic axis. Science signaling 25 37071733
2019 Hypoxia affects Slc7a5 expression through HIF-2α in differentiated neuronal cells. FEBS open bio 25 30761250
2019 Ubiquitylation and endocytosis of the human LAT1/SLC7A5 amino acid transporter. Scientific reports 24 31728037
2013 [miR-126 inhibits colon cancer proliferation and invasion through targeting IRS1, SLC7A5 and TOM1 gene]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 24 23981989
2021 LINC00857 promotes cell proliferation and migration in colorectal cancer by interacting with YTHDC1 and stabilizing SLC7A5. Oncology letters 23 34122629
2020 Intervening upregulated SLC7A5 could mitigate inflammatory mediator by mTOR-P70S6K signal in rheumatoid arthritis synoviocytes. Arthritis research & therapy 23 32867828
2019 Tumor Suppressor miR-184 Enhances Chemosensitivity by Directly Inhibiting SLC7A5 in Retinoblastoma. Frontiers in oncology 23 31803607
2018 Up-regulation of long noncoding RNA MINCR promotes non-small cell of lung cancer growth by negatively regulating miR-126/SLC7A5 axis. Biochemical and biophysical research communications 23 30528230
2024 YAP/TAZ mediates resistance to KRAS inhibitors through inhibiting proapoptosis and activating the SLC7A5/mTOR axis. JCI insight 22 39704172
2021 Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo. International journal of molecular sciences 22 33567754
2018 l-Leucine influx through Slc7a5 regulates inflammatory responses of human B cells via mammalian target of rapamycin complex 1 signaling. Modern rheumatology 22 30092695
2013 Cloning, large scale over-expression in E. coli and purification of the components of the human LAT 1 (SLC7A5) amino acid transporter. The protein journal 22 23912240
2021 Circular RNA circ-FAM158A promotes retinoblastoma progression by regulating miR-138-5p/SLC7A5 axis. Experimental eye research 20 34102206
2007 A simplified method for generating oligodendrocyte progenitor cells from neural precursor cells isolated from the E16 rat spinal cord. Acta neurobiologiae experimentalis 20 18320715
2024 Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay. Molecular biomedicine 19 38556586
2023 SRC2 controls CD4+ T cell activation via stimulating c-Myc-mediated upregulation of amino acid transporter Slc7a5. Proceedings of the National Academy of Sciences of the United States of America 19 37094160
2014 A single nucleotide polymorphism in SLC7A5 is associated with gastrointestinal toxicity after high-dose melphalan and autologous stem cell transplantation for multiple myeloma. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 19 24704384
2021 SLC7A5 is linked to increased expression of genes related to proliferation and hypoxia in estrogen‑receptor‑positive breast cancer. Oncology reports 18 34792178
2020 Human induced pluripotent stem cells (BIONi010-C) generate tight cell monolayers with blood-brain barrier traits and functional expression of large neutral amino acid transporter 1 (SLC7A5). European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 18 33011235
2016 SLC7A5 Functions as a Downstream Target Modulated by CRKL in Metastasis Process of Gastric Cancer SGC-7901 Cells. PloS one 18 27846244
2015 Aryl hydrocarbon receptor-dependent up-regulation of the heterodimeric amino acid transporter LAT1 (SLC7A5)/CD98hc (SLC3A2) by diesel exhaust particle extract in human bronchial epithelial cells. Toxicology and applied pharmacology 18 26621329
1999 Cutting edge: primary structure of the light chain of fusion regulatory protein-1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost identical to the amino acid transporter E16. Journal of immunology (Baltimore, Md. : 1950) 18 10072483
2024 Cancer-associated fibroblasts-derived exosomal METTL3 promotes the proliferation, invasion, stemness and glutaminolysis in non-small cell lung cancer cells by eliciting SLC7A5 m6A modification. Human cell 17 38625505
2020 Regulation of Melanogenesis by the Amino Acid Transporter SLC7A5. The Journal of investigative dermatology 17 32240722
2021 Metabolic adaptations to hypoxia in the neonatal mouse forebrain can occur independently of the transporters SLC7A5 and SLC3A2. Scientific reports 16 33907288
2021 CircZNF124 regulates cell proliferation, leucine uptake, migration and invasion by miR-199b-5p/SLC7A5 pathway in endometrial cancer. Immunity, inflammation and disease 16 34145797
2007 In utero intraventricular injection and electroporation of E16 rat embryos. Journal of visualized experiments : JoVE 16 18997884
2022 Functional Characterization of the Solute Carrier LAT-1 (SLC7A5/SLC2A3) in Human Brain Capillary Endothelial Cells with Rapid UPLC-MS/MS Quantification of Intracellular Isotopically Labelled L-Leucine. International journal of molecular sciences 15 35408997
2020 LAT1 (SLC7A5) Overexpression in Negative Her2 Group of Breast Cancer: A Potential Therapy Target. Asian Pacific journal of cancer prevention : APJCP 15 32458655
2022 Neuronal allodynic mechanisms of Slc7a5 (LAT1) in the spared nerve injury rodent model of neuropathic pain. Pflugers Archiv : European journal of physiology 14 35048187
2022 The role of L-type amino acid transporter 1 (Slc7a5) during in vitro myogenesis. American journal of physiology. Cell physiology 14 35848618
2023 LAT1 (SLC7A5) catalyzes copper(histidinate) transport switching from antiport to uniport mechanism. iScience 13 37692288
2021 OIP5-AS1 contributes to the development in endometrial carcinoma cells by targeting miR-152-3p to up-regulate SLC7A5. Cancer cell international 13 34419049
2025 SLC7A5 is required for cancer cell growth under arginine-limited conditions. Cell reports 12 39756034
2025 SLC7A5/E2F1/PTBP1/PKM2 axis mediates progression and therapy effect of triple-negative breast cancer through the crosstalk of amino acid metabolism and glycolysis pathway. Cancer letters 12 40054655
2024 TRIM35 triggers cardiac remodeling by regulating SLC7A5-mediated amino acid transport and mTORC1 activation in fibroblasts. Cell communication and signaling : CCS 12 39304904
2020 Putative roles of SLC7A5 (LAT1) transporter in pain. Neurobiology of pain (Cambridge, Mass.) 12 32715162
2014 Overview of the glucansucrase equipment of Leuconostoc citreum LBAE-E16 and LBAE-C11, two strains isolated from sourdough. FEMS microbiology letters 12 25790502
2021 The rs113883650 variant of SLC7A5 (LAT1) gene may alter brain phenylalanine content in PKU. Molecular genetics and metabolism reports 11 33868932
2021 IL-18-Mediated SLC7A5 Overexpression Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via the c-MYC Pathway. Frontiers in cell and developmental biology 11 34977008
2016 The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum. Journal of neuroscience research 11 27735078
1999 Expression of E16/CD98LC/hLAT1 is responsive to 2,3,7,8-tetrachlorodibenzo-p-dioxin. FEBS letters 11 10622740
2024 SLC7A5 correlated with malignancies and immunotherapy response in bladder cancer. Cancer cell international 10 38790003
2024 MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression. The clinical respiratory journal 10 38987867
2024 Exosomal miR-126-3p: Potential protection against vascular damage by regulating the SLC7A5/mTOR Signalling pathway in human umbilical vein endothelial cells. Scandinavian journal of immunology 10 39008522
2021 Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark. Molecules (Basel, Switzerland) 10 34770970
2020 Slc7a5 alters Kvβ-mediated regulation of Kv1.2. The Journal of general physiology 10 32311044
2019 Similarities and differences in tissue distribution of DLK1 and DLK2 during E16.5 mouse embryogenesis. Histochemistry and cell biology 10 30888503
2025 Amino acid transporter LAT1 (SLC7A5) promotes metabolic rewiring in TNBC progression through the L-Trp/QPRT/NAD+ pathway. Journal of experimental & clinical cancer research : CR 9 40611146
2024 Leucine-Mediated SLC7A5 Promotes Milk Protein and Milk Fat Synthesis through mTOR Signaling Pathway in Goat Mammary Epithelial Cells. Journal of agricultural and food chemistry 8 38807030
2022 Circ_0067717 promotes colorectal cancer cell growth, invasion and glutamine metabolism by serving as a miR-497-5p sponge to upregulate SLC7A5. Histology and histopathology 8 35818779
2020 Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels. eLife 8 33164746
2019 A Single Nucleotide Polymorphism in SLC7A5 Was Associated With Clinical Response in Multiple Myeloma Patients. Anticancer research 8 30591441
2011 Hb Phimai [β72(E16)Ser→Thr]: a novel β-globin structural variant found in association with Hb constant spring in pregnancy. Hemoglobin 8 21417566
2024 Amino acid transporter SLC7A5 regulates cell proliferation and secretary cell differentiation and distribution in the mouse intestine. International journal of biological sciences 7 38617535
2024 TP63 transcriptionally regulates SLC7A5 to suppress ferroptosis in head and neck squamous cell carcinoma. Frontiers in immunology 7 39234254
2023 L-type Amino Acid Transporter 1 (SLC7A5)-Mediated Transport of Pregabalin at the Rat Blood-Spinal Cord Barrier and its Sensitivity to Plasma Branched-Chain Amino Acids. Journal of pharmaceutical sciences 7 36627052
2023 Hypoxia-mimetic by CoCl2 increases SLC7A5 expression in breast cancer cells in vitro. BMC research notes 7 38082346
2020 Carriership of the rs113883650/rs2287120 haplotype of the SLC7A5 (LAT1) gene increases the risk of obesity in infants with phenylketonuria. Molecular genetics and metabolism reports 7 32874918
2016 SLC7A5 act as a potential leukemic transformation target gene in myelodysplastic syndrome. Oncotarget 7 26657287
2025 Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis. Molecular medicine (Cambridge, Mass.) 6 40133832
2025 Plumbagin ameliorates ferroptosis of ovarian granulosa cells in polycystic ovary syndrome by down-regulating SLC7A5 m6A methylation modification through inhibition of YTHDF1. Journal of ovarian research 6 40457383
2022 The Nutraceutical Alliin From Garlic Is a Novel Substrate of the Essential Amino Acid Transporter LAT1 (SLC7A5). Frontiers in pharmacology 6 35401172
2022 ZNF24 regulates the progression of KRAS mutant lung adenocarcinoma by promoting SLC7A5 translation. Frontiers in oncology 6 36505791
2019 Hb Sichuan [α67(E16)Thr→Ile, HBA2: c.203C>T]: A Novel Hemoglobin Variant That Can Be Detected by Glycated Hemoglobin Electrophoresis. Hemoglobin 6 30612495
2006 Purification and characterization of chitinases from Clostridium sp. E-16 isolated from the intestinal tract of the South American sea lion (Otaria flavescens). Letters in applied microbiology 6 16869903
2023 Targeted delivery of liposomal Ribociclib to SLC7A5 transporters in breast cancer cells. Investigational new drugs 5 38127209
2022 SLC7A5 expression is up-regulated in peripheral blood T and B lymphocytes of systemic lupus erythematosus patients, associating with renal damage. Clinical immunology (Orlando, Fla.) 5 35346864

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