Affinage

SLC38A2

Sodium-coupled neutral amino acid symporter 2 · UniProt Q96QD8

Audit flag: ungrounded claim
Length
506 aa
Mass
56.0 kDa
Annotated
2026-06-10
91 papers in source corpus 58 papers cited in narrative 58 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

SLC38A2 (SNAT2) is a ubiquitously expressed, Na+-coupled system A neutral amino acid transporter that couples extracellular nutrient availability to cellular amino acid supply, with a 1:1 Na+:amino acid stoichiometry and selectivity for small neutral amino acids including glutamine, alanine, proline, glycine and the system A analog MeAIB (PMID:10930503, PMID:11172802). The transporter adopts an 11-transmembrane topology with an intracellular N-terminus and an extracellular, glycosylated C-terminal region (PMID:29678469); key residues define its transport mechanism — Asn82 in TM1 and a TM1/TM8 Na+ site (Thr384) coordinate Na+ binding (PMID:18319257, PMID:19589779), a C-terminal histidine (H504) confers allosteric pH sensitivity (PMID:16629640), and the extracellular C-terminal tail acts as a voltage regulator of translocation (PMID:21158741); SNAT2 additionally carries a substrate-independent anion leak conductance dissociable from amino acid transport (PMID:17237199). SNAT2 expression and surface abundance are controlled by amino acid availability through GCN2/CDK7-dependent ATF4 transcription acting at an intronic AARE bound by ATF/C/EBP factors, eIF2alpha-dependent IRES-mediated translation, and JNK signaling (PMID:16621798, PMID:16445384, PMID:17488712, PMID:30857869), while hormonal and dietary cues converge on dedicated promoter elements — a CRE for cAMP/glucagon, an estrogen response element bound by ERalpha, a ChREBP-repressed ChoRE, and HIF-1alpha under hypoxia (PMID:21386061, PMID:25056967, PMID:33225719, PMID:31152137). Surface levels are further set post-translationally: insulin and osmotic stress mobilize a TGN-stored SNAT2 pool to the plasma membrane via PI3K-dependent trafficking (PMID:11834730, PMID:17050538), and Nedd4-2-mediated polyubiquitination of N-terminal lysines drives endocytosis and proteasomal degradation, with substrate occupancy and Na+ availability tuning protein stability (PMID:17003038, PMID:25653282, PMID:29467657). Beyond transport, SNAT2 functions as a transceptor whose occupancy represses its own transcription and couples amino acid status to mTORC1 and downstream protein synthesis and proteolysis (PMID:17488712, PMID:17429052, PMID:18650482). These activities underpin diverse physiological roles: SNAT2-driven osmolyte accumulation mediates regulatory volume increase under hypertonic stress (PMID:15922329, PMID:16734764), placental SNAT2 supports fetal growth (PMID:34406367), it supplies proline for osteoblast differentiation and bone formation (PMID:35261338, PMID:36213239), protects cells from ferroptosis via mTORC1 and a GSH-GPX4 axis (PMID:36722887, PMID:41715163), regulates endothelial NO production and blood pressure (PMID:40901922), and sustains glutamine-dependent anti-tumor dendritic cell and T-cell immunity (PMID:37407815, PMID:37054944), making it a target in cancer and cardiovascular disease (PMID:36210829, PMID:38949026, PMID:41067488).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Established the molecular identity of system A transport by cloning a Na+-dependent neutral amino acid transporter and defining its substrate range, stoichiometry, and ion dependence.

    Evidence Cloning from HepG2 cells and functional expression with radiolabeled transport assays

    PMID:10930503

    Open questions at the time
    • No structural model or topology at this stage
    • Physiological regulation not yet addressed
  2. 2001 High

    Showed that SNAT2 is the adaptively regulated arm of system A, answering how cells match transport capacity to amino acid demand.

    Evidence Northern blotting and transport assays under amino acid deprivation/supplementation in fibroblasts

    PMID:11172802

    Open questions at the time
    • Transcriptional mechanism of adaptive regulation not defined
    • Distinction from osmotic regulation unaddressed
  3. 2001 Medium

    Identified hypertonic stress as a second, protein-synthesis-dependent inducer of SNAT2, separating osmotic from nutritional regulation.

    Evidence Transport assays and Northern blotting with cycloheximide/actinomycin D in endothelial cells

    PMID:11322785

    Open questions at the time
    • Identity of the required new protein unknown
    • Signaling pathway not dissected
  4. 2002 High

    Demonstrated that SNAT2 activity is acutely controlled by trafficking, not only transcription, with insulin recruiting an intracellular pool to the membrane via PI3K.

    Evidence Surface biotinylation, pharmacological inhibition (chloroquine, wortmannin) and insulin stimulation in L6 myotubes; ATA2 redistribution in regenerating rat liver

    PMID:11834730 PMID:12054432

    Open questions at the time
    • Identity of the storage compartment not yet resolved
    • Trafficking machinery uncharacterized
  5. 2006 High

    Resolved the transcriptional and translational basis of amino-acid-induced SNAT2, locating the AARE to the first intron and showing eIF2alpha-dependent IRES translation, while confirming osmotic induction uses a distinct route.

    Evidence Reporter/EMSA/ChIP of ATF/C/EBP binding, eIF2alpha mutant cells, IRES reporters and in vitro translation in HepG2 and fibroblasts

    PMID:16445384 PMID:16621798

    Open questions at the time
    • Upstream kinase coupling GCN2 to transcription not yet identified
    • Cell-type generality of IRES use unclear
  6. 2006 High

    Defined SNAT2 as a transceptor and identified parallel sensing pathways, showing JNK drives its induction during withdrawal while the transporter itself represses its own gene during sufficiency.

    Evidence shRNA, transporter chimeras, JNK assays and amino acid supplementation in L6 myotubes

    PMID:17488712

    Open questions at the time
    • Molecular signal emanating from occupied transporter unknown
    • Domain mediating the transceptor signal not mapped here
  7. 2006 High

    Established post-translational control of SNAT2 surface abundance through Nedd4-2-mediated polyubiquitination, endocytosis and proteasomal degradation.

    Evidence Oocyte/CHO expression, RNAi, catalytically dead mutant, MG132 and co-localization studies

    PMID:17003038

    Open questions at the time
    • Specific lysine acceptor sites not yet mapped
    • Signals activating Nedd4-2 toward SNAT2 unknown
  8. 2006 High

    Located the regulated intracellular SNAT2 pool to the trans-Golgi network and showed insulin mobilizes it independently of GLUT4 vesicles.

    Evidence Live imaging of EGFP-ATA2, syntaxin 6/EEA1 co-localization and brefeldin A inhibition in 3T3-L1 adipocytes

    PMID:17050538

    Open questions at the time
    • Vesicle tethering/fusion machinery unidentified
    • Whether all stimuli use the same TGN pool unresolved
  9. 2005 High

    Connected SNAT2 induction to a physiological outcome, showing it is required for osmolyte accumulation and regulatory volume increase under hypertonic stress.

    Evidence siRNA knockdown, transport assays, intracellular amino acid and cell volume measurements in fibroblasts

    PMID:15922329 PMID:16734764

    Open questions at the time
    • Transcription factors driving osmotic induction not identified here
    • In vivo relevance to tissues untested at this stage
  10. 2008 High

    Linked SNAT2 transport to mTOR-dependent protein synthesis and proteolysis, defining its role in nutrient signaling and muscle protein balance.

    Evidence MeAIB inhibition, acidosis, siRNA and mTOR/PI3K inhibitors with proteolysis and pathway readouts in L6 cells

    PMID:17429052 PMID:18650482

    Open questions at the time
    • Direct biochemical coupling of SNAT2 to mTORC1 not shown
    • In vivo muscle wasting causation not established here
  11. 2009 High

    Mapped the transport mechanism at residue resolution, identifying Na+-coordinating residues and a substrate-independent anion leak conductance.

    Evidence Site-directed mutagenesis (N82, T384, H304, H504), DEPC modification, electrophysiology and homology modeling in oocytes

    PMID:16629640 PMID:17237199 PMID:18319257 PMID:19589779

    Open questions at the time
    • No experimental high-resolution structure
    • Physiological role of the anion leak unknown
  12. 2014 High

    Expanded the regulatory network to hormonal and dietary inputs by identifying functional CRE, ERE and ChoRE promoter elements and their bound factors and co-factors.

    Evidence Promoter reporter mutagenesis, EMSA, ChIP, co-IP and MS-proteomics in hepatocytes, mammary tissue and rat dietary models

    PMID:21386061 PMID:25056967 PMID:33225719

    Open questions at the time
    • Integration of multiple cis-elements in a single locus not modeled
    • Tissue-specific element usage incompletely mapped
  13. 2015 High

    Refined post-translational regulation by mapping N-terminal lysine ubiquitination sites and showing substrate/Na+ occupancy and lipid signals tune SNAT2 stability.

    Evidence Lysine-to-alanine mutagenesis, chimeric transporters, proteasome inhibition and Nedd4-2 silencing in L6/HeLa cells; IUGR placenta correlation

    PMID:25653282 PMID:26374858 PMID:29467657

    Open questions at the time
    • Full set of E3 ligases beyond Nedd4-2 not enumerated here
    • How substrate occupancy transmits to N-terminal degron unresolved
  14. 2019 High

    Identified CDK7 as a GCN2-dependent effector required for adaptive SNAT2 transcription, refining the amino acid response pathway.

    Evidence Pharmacological CDK7 inhibition with drug-resistant rescue and GCN2 epistasis in amino-acid-deprived cells

    PMID:30857869

    Open questions at the time
    • Direct CDK7 substrate linking to ATF4 not defined
    • Whether CDK7 acts at the SNAT2 locus directly unclear
  15. 2022 High

    Established in vivo physiological roles for SLC38A2 in fetal growth and skeletal biology through tissue-specific genetic ablation.

    Evidence Placenta-specific shRNA knockdown and osteoblast/Prrx1Cre conditional knockout mice with transport, metabolomic and phenotypic readouts

    PMID:34406367 PMID:35261338 PMID:36213239

    Open questions at the time
    • Compensation by other system A transporters not fully resolved
    • Mechanistic coupling of proline supply to differentiation programs incompletely defined
  16. 2023 High

    Implicated SLC38A2-mediated glutamine uptake in immune cell function and ferroptosis resistance, broadening its role to anti-tumor immunity and cell-death protection.

    Evidence Genetic loss-of-function with FLCN-TFEB epistasis in dendritic cells, XBP1 promoter regulation in T cells, and gain/loss with mTORC1 epistasis in renal ferroptosis models

    PMID:36722887 PMID:37054944 PMID:37407815

    Open questions at the time
    • Direct biochemical link between glutamine flux and TFEB/ferroptosis machinery not fully reconstituted
    • Relative contribution of transport vs signaling per context unresolved
  17. 2024 High

    Dissected a ubiquitin-code switch controlling SNAT2 surface levels in cancer, where UBE2C monoubiquitination blocks degradative K63 chains and EPN1-mediated endocytosis to promote metastasis.

    Evidence Site-specific ubiquitin acceptor mutagenesis (K33/K59), endocytosis and VEGFC secretion assays, and in vivo/PDX bladder cancer models

    PMID:38949026

    Open questions at the time
    • Generality of the mono-/polyubiquitin switch beyond bladder cancer untested
    • Deubiquitinases counteracting this switch unidentified
  18. 2025 High

    Defined cardiovascular and metabolic roles for SLC38A2, linking endothelial glutamine uptake to NO/blood pressure and ATF4-driven SLC38A2 to vascular remodeling, plus a NERP-4/SNAT2 axis in insulin secretion.

    Evidence Endothelial and VSMC-specific knockouts, ChIP of ATF4 at the promoter, MeAIB inhibition, and islet/db/db models

    PMID:38071217 PMID:40901922 PMID:41067488

    Open questions at the time
    • Therapeutic window for SNAT2 inhibition across tissues unknown
    • Cross-talk between vascular and metabolic SNAT2 functions unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • How occupancy of SNAT2 generates the transceptor signal that biochemically couples to mTORC1, GCN2 and its own transcriptional repression remains undefined at the molecular level.
  • No reconstituted signaling complex linking transporter occupancy to mTORC1/GCN2
  • No high-resolution structure to rationalize transport vs sensing states
  • Direct downstream effectors of the self-repressive transceptor signal unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 7 GO:0140299 molecular sensor activity 2
Localization
GO:0005886 plasma membrane 6 GO:0005768 endosome 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-382551 Transport of small molecules 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953897 Cellular responses to stimuli 4
Partners
ATF4CHREBPEPN1ESR1FLCNNEDD4LUBE2CXBP1

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Human ATA2/SLC38A2 encodes a 506 amino acid Na+-dependent neutral amino acid transporter (system A) with Na+:amino acid stoichiometry of 1:1, sensitive to pH and Li+-intolerant, transporting alpha-(methylamino)isobutyric acid (MeAIB) and other neutral amino acids when expressed in mammalian cells. Cloning from HepG2 cells, functional expression in mammalian cells, transport assays with radiolabeled substrates, kinetic characterization Biochimica et biophysica acta High 10930503
2001 ATA2/SLC38A2 mRNA expression is adaptively regulated by amino acid availability: amino acid starvation of human fibroblasts increases ATA2 mRNA and system A transport activity, and supplementation with system A substrates (but not other amino acids) suppresses both ATA2 mRNA and transport activity. Northern blotting, radiolabeled amino acid transport assays in cultured human fibroblasts under amino acid deprivation/supplementation conditions FEBS letters High 11172802
2001 Hypertonic stress induces ATA2/SLC38A2 mRNA expression and system A transport activity in porcine endothelial cells; cycloheximide and actinomycin D block both responses, indicating that an earlier protein synthesis step is required. Radiolabeled transport assays, Northern blotting, pharmacological inhibition with cycloheximide and actinomycin D in endothelial cells Biochemical and biophysical research communications Medium 11322785
2002 Insulin stimulates System A (SNAT2/SLC38A2) transport activity in L6 skeletal muscle cells by recruiting SAT2 from an endosomal compartment to the plasma membrane in a phosphatidylinositol 3-kinase (PI3K)-dependent manner; chloroquine (which impairs endosomal recycling) blocks both insulin-stimulated System A activity and plasma membrane SAT2 recruitment without affecting PKB or GSK3 phosphorylation or GLUT4 translocation. Cell surface biotinylation, Western blotting, pharmacological inhibition (chloroquine, wortmannin), insulin stimulation assays in L6 myotubes The Journal of biological chemistry High 11834730
2002 After partial hepatectomy in rats, ATA2-mediated system A amino acid transport activity increases by redistribution of ATA2 protein to the plasma membrane, not by increased ATA2 mRNA levels (Northern analysis showed no change in steady-state mRNA). Immunodetection of ATA2 in isolated liver plasma membrane and lysate fractions, Northern blotting, partial hepatectomy model Archives of biochemistry and biophysics Medium 12054432
2002 Transcriptional activation of the ATA2/SLC38A2 gene by amino acid deprivation differs mechanistically from asparagine synthetase: ATA2 mRNA increases within 2–4 h (vs. 4 h lag for AS), is largely independent of de novo protein synthesis, and is not induced by glucose deprivation. mRNA quantification by Northern/RT-PCR, cycloheximide treatment, glucose deprivation, amino acid-free Krebs buffer incubations in HepG2 cells The Journal of nutrition Medium 12368390
2004 Hypertonic stimulation of system A transport activity requires synthesis of new SNAT2 protein; transcription inhibitor DRB suppresses the hypertonic increase in plasma membrane SNAT2 and fully blocks system A stimulation, whereas DRB does not fully block the adaptive (amino acid starvation) increase in SNAT2 at the plasma membrane. Biotinylation of surface proteins, immunocytochemistry, transcription inhibition (DRB), Western blotting in human fibroblasts Biochimica et biophysica acta Medium 15581851
2005 siRNA-mediated knockdown of SNAT2 in human fibroblasts under hypertonic conditions prevents the increase in system A transport activity, blocks intracellular amino acid pool expansion, and markedly delays cell volume recovery, demonstrating that SNAT2 induction is essential for regulatory volume increase. siRNA knockdown, radiolabeled amino acid transport assays, cell volume measurements, intracellular amino acid quantification FEBS letters High 15922329
2005 SNAT2 is expressed in neuronal cell bodies, processes, axonal shafts (but excluded from terminals), and in perivascular astrocytic end-feet and Bergmann glia in the rat CNS; enriched in spinal cord/brainstem and preferentially found in glutamatergic (not GABAergic) neurons. Immunohistochemistry with specific antisera, confocal microscopy, ultrastructural (EM) studies in rat brain Neuroscience Medium 15561425
2006 Amino acid starvation-induced upregulation of SNAT2 requires eIF2alpha phosphorylation (blunted in cells with a non-phosphorylatable eIF2alpha mutant), increased gene transcription, and IRES-mediated cap-independent translation; hypertonic stress induction of SNAT2 is independent of eIF2alpha phosphorylation. Transport assays, mRNA/protein quantification, eIF2alpha phosphorylation-deficient mutant cells, IRES reporter constructs, in vitro translation, cycloheximide and actinomycin D inhibition The Journal of biological chemistry High 16621798
2006 The amino acid response element (AARE) regulating SNAT2 transcription upon amino acid limitation localizes to the first intron; ATF and C/EBP family members bind this intronic enhancer (not the promoter) in vitro and in vivo, with specific family members either activating or repressing SNAT2 transcription; amino acid deprivation increases RNA pol II recruitment to the SNAT2 promoter. Luciferase reporter assays, EMSA, ChIP assays, exogenous ATF/C/EBP expression, mRNA quantification in HepG2 and fibroblast cells The Biochemical journal High 16445384
2006 Cortisol stimulates system A amino acid transport activity and increases SNAT2 mRNA/protein expression in BeWo placental cells; lower cortisol concentrations cause relocalization of SNAT2 transporter. Radiolabeled MeAIB transcellular transport assays, Northern and Western blotting, immunocytochemistry in BeWo cells American journal of physiology. Endocrinology and metabolism Medium 16621896
2006 pH sensitivity of SNAT2 transport involves a conserved C-terminal histidine residue (H504): DEPC modification reduces pH-sensitivity and blocks decreased Na+ affinity at low pH; H504A mutation produces reduced, DEPC-resistant pH-sensitivity without changing Na+ affinity at low pH. This suggests an allosteric H+-modifier site on C-terminal histidine that influences Na+ binding. DEPC chemical modification, site-directed mutagenesis (H504A), functional transport assays in Xenopus oocytes expressing SNAT2 and SNAT5 The Biochemical journal High 16629640
2006 SNAT2 activity is regulated by at least two amino acid sensor pathways: during amino acid withdrawal, JNK is activated and induces SNAT2 expression via an intronic nutrient-sensitive domain; large neutral amino acids (Tyr, Gln) inhibit JNK activation and SNAT2 upregulation. Additionally, SNAT2 itself provides a repressive signal for its own gene transcription during amino acid sufficiency (transceptor function), demonstrated by shRNA and transporter chimeras. shRNA knockdown, transporter chimera experiments, JNK activity assays, reporter gene assays, amino acid supplementation experiments in L6 myotubes The Journal of biological chemistry High 17488712
2006 Ubiquitin ligase Nedd4-2 downregulates ATA2/SNAT2 transport activity at the cell surface by promoting polyubiquitination of ATA2 leading to endocytosis and proteasomal degradation; catalytically dead Nedd4-2 mutant had no effect; RNAi knockdown of Nedd4-2 increased ATA2 activity with decreased ATA2 polyubiquitination; Nedd4-2 co-localizes with EGFP-ATA2 at the plasma membrane. Xenopus oocyte expression, CHO cell transfection, RNAi knockdown, immunofluorescence, co-localization studies, proteasome inhibitor (MG132) experiments The Journal of biological chemistry High 17003038
2006 ATA2/SNAT2 is stored at the trans-Golgi network (TGN) in 3T3-L1 adipocytes (co-localizing with syntaxin 6, not EEA1); insulin stimulates release of ATA2-containing vesicles from this TGN compartment to the plasma membrane. The ATA2 storage vesicles are distinct from GLUT4-containing vesicles. Brefeldin A (TGN exit blocker) inhibits insulin-stimulated MeAIB uptake more profoundly than glucose uptake. Live cell imaging of EGFP-ATA2 fusion protein, immunofluorescence with TGN marker syntaxin 6 and endosomal marker EEA1, brefeldin A inhibition, transport assays in 3T3-L1 adipocytes The Journal of biological chemistry High 17050538
2006 SNAT2 mediates induction of cell volume recovery (regulatory volume increase, RVI) upon hypertonic exposure: SNAT2-specific siRNA in human fibroblasts prevents system A transport stimulation, reduces intracellular amino acid pool expansion, and significantly delays cell volume recovery; newly synthesized SNAT2 proteins under hypertonic conditions are preferentially targeted to the cell membrane. siRNA, transport assays, intracellular amino acid quantification, cell volume measurements in human fibroblasts Acta physiologica (Oxford, England) High 16734764
2007 SNAT2 mediates an anion leak conductance that does not require substrate transport; transported substrates (L-alanine, L-glutamine, MeAIB) inhibit the anion leak with different potencies; mutation H304A abolishes alanine transport but retains anion leak current; both Na+ and substrate can bind H304A transporter; anion selectivity follows SCN->NO3->I->Br->Cl->Mes-. Whole-cell electrophysiology (patch clamp), site-directed mutagenesis (H304A), substrate binding assays in Xenopus oocytes and HEK293 cells Biophysical journal High 17237199
2007 SNAT2 inhibition by methylaminoisobutyrate (MeAIB), metabolic acidosis (pH 7.1), or siRNA knockdown depletes intracellular glutamine and indirectly depletes leucine (maintained by the glutamine gradient via system L), leading to impaired mTOR signaling (reduced p70S6K1, S6, and 4E-BP1 phosphorylation) and impaired protein synthesis in L6 skeletal muscle cells. Competitive substrate inhibition (MeAIB), pH manipulation, siRNA knockdown, intracellular amino acid profiling, mTOR pathway Western blotting in L6 cells Journal of the American Society of Nephrology : JASN High 17429052
2008 SNAT2 inhibition by MeAIB or metabolic acidosis (pH 7.1) stimulates proteolysis in L6 myotubes via both mTOR and PI3K signaling pathways; partial SNAT2 siRNA silencing stimulates proteolysis and impairs insulin signaling through PI3K; acidosis shifts insulin dose-response for suppression of proteolysis rightward, demonstrating that SNAT2 provides a link between acidosis, insulin resistance, and protein wasting. MeAIB inhibition, pH manipulation, siRNA knockdown, proteasome inhibition, mTOR and PI3K inhibitors, proteolysis rate measurement, Western blotting in L6 cells Journal of the American Society of Nephrology : JASN High 18650482
2008 SNAT2 transport activity is regulated by amino acid substrate availability and Na+; the insulin-induced upregulation of system A in L6 cells is mediated by increased Vmax (not Km), and is blocked by chloroquine and wortmannin; amino acid deprivation induction is blocked by PD98059 (MEK inhibitor) and SP600125 (JNK inhibitor); osmotic shock induction is blocked by neither chloroquine/wortmannin nor PD98059/SP600125, indicating distinct mechanisms. Radiolabeled transport kinetics, pharmacological inhibitor panel (chloroquine, wortmannin, PD98059, SP600125, SB202190), Western blotting, RT-PCR in L6 rat skeletal muscle cells Amino acids Medium 18330498
2008 Asparagine 82 (N82) in transmembrane domain 1 of SNAT2 is critical for Na+ coordination: N82A mutation virtually eliminates alanine-induced transport current and amino acid uptake, dramatically reduces Na+ affinity (Kna), and increases apparent Km for alanine 27-fold; N82S has intermediate effect. Y337A and R374Q mutations do not abolish transport. Site-directed mutagenesis (N82A, N82S, Y337A, R374Q), electrophysiology, radiolabeled amino acid uptake in Xenopus oocytes The Journal of biological chemistry High 18319257
2008 Despite increased ATF4 binding to the C/EBP-ATF site in the SNAT2 intronic AARE during UPR activation in HepG2 cells, SNAT2 transcription is not enhanced; the UPR suppresses AAR-induced SNAT2 transcription acting downstream of ATF4 binding, associated with lack of H3 hyperacetylation and failure to recruit general transcription factors at the SNAT2 promoter. ChIP assays, luciferase reporter assays, H3 acetylation analysis, ATF4 binding assays, simultaneous AAR+UPR activation in HepG2 cells The Journal of biological chemistry High 18697751
2009 A conserved Na+ binding site in SNAT2 is formed by transmembrane helices 1 and 8: T384A mutation inhibits the anion leak current (which requires Na+ binding) and dramatically lowers Na+ affinity, consistent with homology modeling using LeuT and Mhp1 as templates that predicted a Na+ binding site involving TM1 and TM8. Profile-based sequence analysis, homology modeling (LeuT/Mhp1 templates), site-directed mutagenesis (T384A), electrophysiology, Na+ affinity measurements The Journal of biological chemistry High 19589779
2009 IL-6 stimulates system A amino acid transport and increases SNAT2 (but not SNAT1) mRNA and protein expression in primary human trophoblast cells via a JAK/STAT3 (Tyr705 phosphorylation)-dependent pathway; siRNA knockdown of STAT3 abolishes IL-6-stimulated system A activity and SNAT2 expression. TNF-alpha stimulates system A independently of the JAK/STAT pathway. Radiolabeled transport assays, STAT3 siRNA knockdown, Western blotting (STAT3 phosphorylation), RT-PCR, TNF-alpha and IL-6 treatment of primary human trophoblast cells American journal of physiology. Cell physiology High 19741197
2009 In neocortical neurons, taurine, GABA, and beta-alanine (SLC6 GABA transporter substrates) repress SNAT2 expression more potently (10x) than system A substrates; increased endogenous SNAT2 expression or repression did not affect spontaneous glutamatergic excitatory action-potential frequency or quantal size, suggesting SNAT2 is not required to support neurotransmitter glutamate synthesis in these neurons under physiological conditions. shRNA-mediated SNAT2 induction/repression, electrophysiology (spontaneous excitatory activity), SNAT2 mRNA stability assays, amino acid supplementation in neocortical neurons The Journal of biological chemistry Medium 19240036
2011 Chronic competitive inhibition of SNAT2 (System A) by MeAIB in MCF-7 cells depletes intracellular SNAT2 substrates and branched-chain amino acids (e.g., leucine) but paradoxically elevates mTOR-dependent p70S6K1 phosphorylation; two novel SNAT2-interacting proteins were identified by proteomics of TAP-tag purified SNAT2 fusion proteins, potentially functioning with SNAT2 as a transceptor. Competitive inhibition (MeAIB), intracellular amino acid profiling, mTOR signaling Western blotting, TAP-tag purification followed by proteomic analysis in MCF-7 cells Frontiers in bioscience (Elite edition) Medium 21622135
2011 The C-terminal domain of SNAT2 (extracellular, 13 residues) is an important voltage regulator required for amino acid translocation at negative membrane potentials; deletion of 13 C-terminal residues abolishes transport at negative potentials but preserves transport at positive potentials; the truncation also increases alanine affinity (~3-fold) and Na+ affinity (~2-fold) but does not affect membrane expression. Site-directed deletion mutagenesis, whole-cell electrophysiology, radiolabeled substrate uptake, surface expression assays in Xenopus oocytes The Biochemical journal High 21158741
2011 SNAT2 is the primary L-proline transporter on embryonic stem (ES) cells mediating L-proline-induced differentiation to early primitive ectoderm-like cells; excess SNAT2 substrates (but not non-substrates) prevent L-proline-induced changes in morphology, gene expression, and differentiation kinetics, demonstrating that L-proline uptake through SNAT2 is required for ES cell differentiation. Competitive substrate inhibition with SNAT2 substrates vs. non-substrates, morphology assessment, gene expression analysis, differentiation kinetics in ES cells American journal of physiology. Cell physiology Medium 21346154
2011 The rat SNAT2 gene promoter contains a functional CRE site at -48 bp (highly conserved among rat, mouse, and human) responsible for cAMP/glucagon-stimulated transcription; deletion and mutation analyses, EMSA, and ChIP confirmed that this CRE site mediates SNAT2 regulation by cAMP. A high-protein diet (which increases serum glucagon) also increases SNAT2 mRNA in vivo. 5' deletion analysis of SNAT2 promoter, site-directed mutagenesis of CRE sites, luciferase reporter assays, EMSA, ChIP, forskolin/glucagon treatment in hepatocytes, in vivo dietary manipulation American journal of physiology. Endocrinology and metabolism High 21386061
2013 SNAT2 (SLC38A2) transports anti-[18F]FACBC (a PET radiotracer) with a Km of ~197 µM in Xenopus oocytes expressing SNAT2, demonstrating FACBC is a substrate of SNAT2 (with lower affinity than ASCT2, LAT1, and LAT2). Radiolabeled [14C]FACBC kinetic transport assays in Xenopus oocytes expressing SNAT2, ASCT2, LAT1, or LAT2; Michaelis-Menten kinetics Nuclear medicine and biology Medium 23647854
2014 Only SNAT2 (not SNAT1 or SNAT4) transports betaine with a Km of ~5 mM; betaine uptake by SNAT2 is hyperosmotically inducible in placental trophoblast cells (TR-TBT 18d-1), and SNAT2 protein expression on the plasma membrane is more potently induced by hypertonicity than total SNAT2 expression. [14C]betaine uptake assays, transfection of HEK293 cells with SNAT1, SNAT2, SNAT4, Western blotting for plasma membrane vs. total SNAT2, immunocytochemistry under hypertonic conditions Biochimica et biophysica acta Medium 24434061
2014 17β-estradiol regulates SNAT2 transcription through an estrogen response element (ERE) in the SNAT2 promoter bound by estrogen receptor alpha (ER-α); ER-α binding to the SNAT2 ERE increases progressively during gestation in the mammary gland; the ER-α-ERE complex contains PARP1, Ku70, and GAPDH as co-factors required for estradiol-stimulated promoter activity. In silico ERE identification, luciferase reporter assays with ERE deletion, EMSA with supershift assay, in vivo ChIP during gestation, LC-MS proteomics of the ER-α-ERE complex, siRNA knockdown of co-factors Proceedings of the National Academy of Sciences of the United States of America High 25056967
2015 Ubiquitination of SNAT2 by Nedd4-2 (NEDD4L) is increased in IUGR placentas; increased NEDD4-2 expression and SNAT2 ubiquitination are associated with decreased SNAT2 in the trophoblast microvillous plasma membrane and reduced system A transport activity. mTOR signaling (mTORC1 and mTORC2) is decreased in IUGR, consistent with mTOR regulating SNAT2 trafficking by modulating ubiquitination. Protein fractionation, ubiquitination assays, Western blotting for mTOR pathway components and NEDD4-2, system A transport assays in isolated plasma membranes from IUGR and control placentas Clinical science (London, England : 1979) Medium 26374858
2015 Linoleic acid (unsaturated C18:2 fatty acid) reduces stress-induced SNAT2 protein and membrane transport activity via the ubiquitin-proteasome system; mutating seven N-terminal lysyl-ubiquitination sites of SNAT2 to alanine protects against linoleic acid-induced degradation; Nedd4.2 is upregulated by linoleic acid but Nedd4.2 shRNA silencing does not curb fatty acid-induced SNAT2 loss. Proteasome inhibition, shRNA Nedd4.2 silencing, SNAT2 N-terminal lysine-to-alanine mutations, transport assays, Western blotting in L6 myotubes and HeLa cells The Journal of biological chemistry High 25653282
2015 Hyperosmotic stress response involves coordinated induction of SNAT2 and GADD34; SNAT2-mediated amino acid uptake is enhanced by increased GADD34 levels through decreased eIF2alpha phosphorylation; GADD34 induction during hyperosmotic stress is controlled by c-Jun-binding CRE in GADD34 promoter and mRNA stabilization (not ATF4, which is not translated despite eIF2alpha phosphorylation). GADD34 expression analysis, eIF2alpha phosphorylation assays, reporter gene assays, mRNA stability assays, amino acid transport assays in response to hyperosmotic stress The Journal of biological chemistry Medium 26041779
2016 Net glutamine uptake in HeLa and 143B cancer cells does not depend on ASCT2 (deletion does not reduce cell growth) but requires expression of SNAT1 and SNAT2; ASCT2 deletion causes amino acid starvation response and upregulation of SNAT1. Silencing GCN2 in the ASCT2-/- background reduces cell growth. CRISPR/gene deletion of ASCT2, SNAT siRNA silencing, cell growth assays, GCN2 siRNA in knockout background, radiolabeled transport assays The Journal of biological chemistry High 27129276
2016 A disulfide bond exists between Cys245 and Cys279 in SNAT2; this disulfide bond does not affect cell surface trafficking or transport function, but marks proximity in the extracellular domain. Site-directed mutagenesis (C245A, C279A, C245,279A double mutant), mPEG-Mal chemical modification with/without DTT reduction, transport assays in HEK293 cells PloS one Medium 27355203
2018 SNAT2 membrane topology consists of 11 transmembrane domains with an intracellular N-terminus and extracellular C-terminus; three N-glycosylation sites were confirmed at the largest extracellular loop. mPEG-Mal chemical modification, protease cleavage assays, immunofluorescence, glycosylation analysis in rat SNAT2 Biochimica et biophysica acta. Biomembranes Medium 29678469
2018 SNAT2 protein stability is regulated by substrate (AA and Na+) availability: AA withdrawal increases SNAT2 protein stability; provision of SNAT2 substrates (MeAIB, glutamine) but not non-substrates represses this stabilization; the N-terminal cytoplasmic tail of SNAT2 (containing lysyl residues) is required for substrate-induced instability; grafting the SNAT2 N-terminal tail onto SNAT5 (which lacks adaptive regulation) confers substrate-induced changes in SNAT5 chimera stability. Extracellular Na+ removal destabilizes SNAT2 regardless of substrate presence. Chimeric transporter construction, N-terminal lysine-to-alanine mutations, Western blotting for protein stability, substrate provision experiments in HeLa cells Frontiers in pharmacology High 29467657
2019 CDK7 activity is upregulated in amino acid-deprived cells in a GCN2-dependent manner and is required for the SNAT2 adaptive transcription response; pharmacological inhibition of CDK7 with THZ-1 attenuates ATF4 expression and blocks system A adaptation; this effect is mitigated in cells expressing a drug-resistant CDK7 form. GSK3, MEK-ERK, mTORC1, and p38 inhibition have no detectable effect on System A adaptation. Pharmacological CDK inhibitors (roscovitine, flavopiridol, THZ-1), drug-resistant CDK7 rescue construct, shRNA GSK3, CDK7 activity assays, System A transport assays in amino acid-deprived cells Biochimica et biophysica acta. Molecular cell research High 30857869
2019 SNAT2 in breast cancer MCF7 cells is regulated by both ERα and HIF-1α; under hypoxia, regulation shifts from ERα-dependent to predominantly HIF-1α-dependent (both regulatory elements overlap in SNAT2 cis-regulatory region); downregulation by fulvestrant (ER antagonist) is reverted in hypoxia; SNAT2 overexpression in vivo causes complete resistance to antiestrogen therapy. Reporter assays, HIF-1α/ERα binding site analysis, fulvestrant treatment under normoxia vs. hypoxia, in vitro overexpression/growth assays, xenograft in vivo studies Proceedings of the National Academy of Sciences of the United States of America High 31152137
2020 ChREBP represses SNAT2 expression in response to a high-carbohydrate diet by binding to a carbohydrate response element (ChoRE) at -160 bp upstream of the SNAT2 transcriptional start site, and recruits the co-repressor SMRT; confirmed by ChIP-qPCR in vivo and immunoprecipitation showing ChREBP-SMRT interaction. Luciferase reporter assays with ChoRE, immunoprecipitation (ChREBP-SMRT), in vivo ChIP, high-sucrose diet rat model, Western blotting American journal of physiology. Endocrinology and metabolism High 33225719
2021 Placenta-specific Slc38a2/SNAT2 knockdown (59% reduction via lentiviral shRNA) in mice causes fetal growth restriction: reduces near-term fetal and placental weight, fetal viability, trophoblast plasma membrane SNAT2 protein abundance, and placental system A (MeAIB) uptake, directly demonstrating that SNAT2 deficiency in the placenta mechanistically causes restricted fetal growth. Lentiviral shRNA transduction of blastocysts, 14C-MeAIB uptake assay, Western blotting, fetal/placental weight measurements Clinical science (London, England : 1979) High 34406367
2022 SLC38A2 provides proline to osteoblasts to fulfill the unique biosynthetic demand imposed by differentiation; osteoblast-associated proteins (RUNX2, OSX, OCN, COL1A1) are enriched in proline; genetic ablation of SLC38A2 in osteoblasts limits osteoblast differentiation and bone formation in mice; proline from SLC38A2 is primarily incorporated into nascent protein with little metabolism. Bioinformatic amino acid composition analysis, osteoblast-specific Slc38a2 genetic ablation (mouse), metabolomics (proline tracking), osteoblast differentiation assays eLife High 35261338
2022 SLC38A2 provides proline and alanine to osteoblast lineage cells during postnatal bone homeostasis; genetic ablation of SLC38A2 using Prrx1Cre decreases bone mass in male and female mice due to reduced osteoblast numbers and bone-forming activity, attributable to impaired proliferation and osteogenic differentiation of skeletal stem and progenitor cells. Prrx1Cre-mediated conditional Slc38a2 knockout in mice, μCT bone analysis, histomorphometry, skeletal stem cell proliferation and differentiation assays Frontiers in physiology High 36213239
2022 SNAT2 is responsible for sarcosine and glycine uptake in hyperosmotic-stressed PC-3 prostate cancer cells; hyperosmotic culture increases SNAT2 mRNA/protein and sarcosine uptake ~9-fold; siRNA knockdown of SNAT2 reduces sarcosine uptake Vmax from 2653 to 513 nmol/mg/min without altering Km, indicating SNAT2 accounts for ~80% of hyperosmotic sarcosine transport. Sarcosine is identified as a novel SNAT2 substrate. siRNA knockdown, 14C-sarcosine and 3H-glycine uptake kinetics, RT-PCR, Western blotting in PC-3 cells under isosmotic and hyperosmotic conditions Pflugers Archiv : European journal of physiology Medium 36175560
2022 Identification of a potent SNAT2 inhibitor (MMTC/57E, IC50 0.8–3 µM) using a high-throughput FMP membrane potential assay; the compound discriminates against SNAT1. In combination with the glucose transport inhibitor Bay-876, the SNAT2 inhibitor halts proliferative growth of MDA-MB-231 and HPAFII cancer cells, demonstrating synergy between SNAT2 (glutaminolysis) and glucose transport inhibition. High-throughput FLIPR membrane potential assay screening, IC50 determination, SNAT1/SNAT2 selectivity assays, cancer cell proliferation assays with combination treatment Frontiers in pharmacology Medium 36210829
2023 In type-1 conventional dendritic cells (cDC1s), SLC38A2-mediated glutamine uptake regulates anti-tumor immunity; tumor cells and cDC1s compete for glutamine via SLC38A2; glutamine signaling via FLCN impinges on TFEB function; SLC38A2 deficiency in cDC1s selectively impairs cDC1 function in vivo and phenocopies FLCN loss; intratumoral glutamine supplementation augments cDC1-mediated CD8+ T cell immunity and overcomes therapeutic resistance. Genetic loss-of-function (SLC38A2 deficiency, FLCN knockout in DCs), TFEB functional assays, nutrient screening, in vivo tumor models, T cell immunity readouts, epistasis (FLCN KO phenocopies SLC38A2 deficiency in a TFEB-dependent manner) Nature High 37407815
2023 XBP1 inhibits SLC38A2 by directly binding to its promoter in cytotoxic T cells in multiple myeloma; SLC38A2 silencing reduces glutamine uptake and causes immune dysfunction of T cells in vitro. Single-cell RNA sequencing, in vitro XBP1 overexpression with promoter binding assay, SLC38A2 siRNA knockdown, glutamine uptake assays, T cell functional assays Cancer letters Medium 37054944
2023 SLC38A2 protects renal medullary collecting duct (MCD) cells from hyperosmolarity-induced ferroptosis; hyperosmotic cell death occurred mainly via ferroptosis and was significantly attenuated by SLC38A2 overexpression and worsened by Slc38a2 deletion/silencing; the osmoprotective effect of SLC38A2 is dependent on mTORC1 activation; Slc38a2-knockout mice showed increased medullary ferroptosis following water restriction. SLC38A2 overexpression, siRNA silencing, Slc38a2 gene deletion, ferroptosis assays, mTORC1 activity assays, water restriction in vivo mouse model eLife High 36722887
2023 NERP-4 (a VGF-derived peptide) acts on SNAT2, increasing uptake of glutamine, alanine, and proline into pancreatic β-cells to stimulate glucose-stimulated insulin secretion; SNAT2 deletion and inhibition abolish the protective effects of NERP-4 on β-cell maintenance in db/db mice. NERP-4 administration to isolated islets and MIN6-K8 cells, SNAT2 deletion and pharmacological inhibition, amino acid uptake assays, insulin secretion assays, Ca2+ influx measurements, db/db mouse model Nature communications High 38071217
2024 UBE2C mediates SNAT2 monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33; monoubiquitination suppresses EPN1-mediated endocytosis of SNAT2, increasing SNAT2 membrane levels; increased membrane SNAT2 facilitates glutamine uptake and metabolism, promoting VEGFC secretion, lymphangiogenesis, and lymph node metastasis in bladder cancer. High-throughput sequencing, site-directed mutagenesis of SNAT2 ubiquitination sites (K33, K59), ubiquitination assays (mono vs. K63-linked poly), endocytosis assays, VEGFC secretion assays, in vitro and in vivo lymphangiogenesis models, patient-derived xenograft The Journal of clinical investigation High 38949026
2025 Endothelial cell-specific Slc38a2 knockout (Slc38a2ΔEC) reduces blood pressure in mice; blockade of SLC38A2 by MeAIB increases NO production via activating the AKT-eNOS pathway by inhibiting EC glutamine uptake; MeAIB lowers blood pressure in high-salt and DOCA-induced hypertensive mouse and rat models. Global and endothelial-specific Slc38a2 knockout mice, scRNA-seq (NO biosynthesis pathway analysis), MeAIB pharmacological inhibition, NO/eNOS/AKT assays, blood pressure measurement in multiple hypertension models Science translational medicine High 40901922
2025 ALDH2 deficiency promotes vascular smooth muscle cell (VSMC) proliferation and neointima formation by upregulating SLC38A2 expression via ATF4; ALDH2 deficiency increases 4-HNE adducted protein accumulation, which activates ATF4 to transcriptionally upregulate SLC38A2; ATF4 knockdown reverses ALDH2 deficiency-induced VSMC proliferation; AAV2-shRNA or MeAIB inhibition of SLC38A2 attenuates neointima formation. VSMC-specific ALDH2 knockout mice, luciferase assays, ChIP-qPCR for ATF4 binding at SLC38A2 promoter, ATF4 siRNA knockdown, AAV2-shRNA SLC38A2 knockdown, MeAIB inhibition, 4-HNE quantification, neointima formation assays Metabolism: clinical and experimental High 41067488
2025 PTCD3 promotes SLC38A2 mRNA stability in an IGF2BP2-dependent manner (m6A modification); PTCD3 knockdown suppresses glutaminolysis and CRC migration/invasion; SLC38A2 overexpression reverses these effects; KAT2A upregulates PTCD3 via H3K27 acetylation. Co-IP, RIP assay, dual-luciferase assay (m6A site), PTCD3 knockdown with SLC38A2 rescue, Western blotting, CRC xenograft model FASEB journal Medium 40304977
2026 L-proline is transported into bovine mammary epithelial cells via SNAT2; intracellular proline binds P4HA2 (prolyl 4-hydroxylase subunit alpha 2), promoting mTOR lysosomal translocation and mTORC1 signaling pathway activation, thereby enhancing milk fat and protein synthesis. Targeted metabolomics, SNAT2 and P4HA2 functional studies in bovine mammary epithelial cells, mTOR lysosomal translocation assays, rumen-protected L-Pro feeding trial in dairy cows Journal of agricultural and food chemistry Medium 42126009
2026 SLC38A2 upregulation by melatonin in the hippocampus protects against Aβ-induced ferroptosis: shRNA-mediated SLC38A2 knockdown in HT22 neurons reduces GSH and GPX4, increases iron and ROS, enhances erastin-induced ferroptosis, and abolishes the protective effect of melatonin, demonstrating SLC38A2 functions through the SLC38A2-GSH-GPX4 axis. shRNA knockdown in HT22 neurons, GSH/GPX4/iron/ROS biochemical assays, erastin-induced ferroptosis, organotypic hippocampal slices, Aβ1-42 oligomer injection mouse model, immunohistochemistry/Western blotting Alzheimer's research & therapy Medium 41715163

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity. Nature 230 37407815
2016 Deletion of Amino Acid Transporter ASCT2 (SLC1A5) Reveals an Essential Role for Transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to Sustain Glutaminolysis in Cancer Cells. The Journal of biological chemistry 211 27129276
2009 IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2. American journal of physiology. Cell physiology 134 19741197
2000 Primary structure, functional characteristics and tissue expression pattern of human ATA2, a subtype of amino acid transport system A. Biochimica et biophysica acta 130 10930503
2019 Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer. Proceedings of the National Academy of Sciences of the United States of America 110 31152137
2007 Distinct sensor pathways in the hierarchical control of SNAT2, a putative amino acid transceptor, by amino acid availability. The Journal of biological chemistry 104 17488712
2006 Amino acid starvation induces the SNAT2 neutral amino acid transporter by a mechanism that involves eukaryotic initiation factor 2alpha phosphorylation and cap-independent translation. The Journal of biological chemistry 91 16621798
2002 Insulin promotes the cell surface recruitment of the SAT2/ATA2 system A amino acid transporter from an endosomal compartment in skeletal muscle cells. The Journal of biological chemistry 84 11834730
2015 Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human IUGR. Clinical science (London, England : 1979) 78 26374858
2011 SNAT2 transceptor signalling via mTOR: a role in cell growth and proliferation? Frontiers in bioscience (Elite edition) 77 21622135
2001 The adaptive regulation of amino acid transport system A is associated to changes in ATA2 expression. FEBS letters 74 11172802
2018 Methionine Promotes Milk Protein and Fat Synthesis and Cell Proliferation via the SNAT2-PI3K Signaling Pathway in Bovine Mammary Epithelial Cells. Journal of agricultural and food chemistry 72 30274521
2006 The role of the neutral amino acid transporter SNAT2 in cell volume regulation. Acta physiologica (Oxford, England) 69 16734764
2007 Acidosis-sensing glutamine pump SNAT2 determines amino acid levels and mammalian target of rapamycin signalling to protein synthesis in L6 muscle cells. Journal of the American Society of Nephrology : JASN 67 17429052
2006 Cortisol stimulates system A amino acid transport and SNAT2 expression in a human placental cell line (BeWo). American journal of physiology. Endocrinology and metabolism 63 16621896
2005 Immunohistochemical localization of the amino acid transporter SNAT2 in the rat brain. Neuroscience 61 15561425
2006 Characterization of the amino acid response element within the human sodium-coupled neutral amino acid transporter 2 (SNAT2) System A transporter gene. The Biochemical journal 60 16445384
2019 Multifaceted regulation of the system A transporter Slc38a2 suggests nanoscale regulation of amino acid metabolism and cellular signaling. Neuropharmacology 49 31574264
2013 Kinetic analyses of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2. Nuclear medicine and biology 47 23647854
2006 Regulation of amino acid transporter ATA2 by ubiquitin ligase Nedd4-2. The Journal of biological chemistry 47 17003038
2001 Osmotic regulation of ATA2 mRNA expression and amino acid transport System A activity. Biochemical and biophysical research communications 46 11322785
2011 The amino acid transporter SNAT2 mediates L-proline-induced differentiation of ES cells. American journal of physiology. Cell physiology 45 21346154
2006 Amino acid transporter ATA2 is stored at the trans-Golgi network and released by insulin stimulus in adipocytes. The Journal of biological chemistry 44 17050538
2008 Inhibition of SNAT2 by metabolic acidosis enhances proteolysis in skeletal muscle. Journal of the American Society of Nephrology : JASN 43 18650482
2022 SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation. eLife 40 35261338
2021 Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice. Clinical science (London, England : 1979) 40 34406367
2009 SNAT2 amino acid transporter is regulated by amino acids of the SLC6 gamma-aminobutyric acid transporter subfamily in neocortical neurons and may play no role in delivering glutamine for glutamatergic transmission. The Journal of biological chemistry 38 19240036
2006 Evidence for allosteric regulation of pH-sensitive System A (SNAT2) and System N (SNAT5) amino acid transporter activity involving a conserved histidine residue. The Biochemical journal 38 16629640
2013 SNAT2 expression and regulation in human growth-restricted placentas. Pediatric research 37 23728383
2008 Despite increased ATF4 binding at the C/EBP-ATF composite site following activation of the unfolded protein response, system A transporter 2 (SNAT2) transcription activity is repressed in HepG2 cells. The Journal of biological chemistry 35 18697751
2004 The synthesis of SNAT2 transporters is required for the hypertonic stimulation of system A transport activity. Biochimica et biophysica acta 34 15581851
2015 Proteasomal modulation of cellular SNAT2 (SLC38A2) abundance and function by unsaturated fatty acid availability. The Journal of biological chemistry 33 25653282
2022 Identification and characterization of a novel SNAT2 (SLC38A2) inhibitor reveals synergy with glucose transport inhibition in cancer cells. Frontiers in pharmacology 32 36210829
2012 Functional RNA interference (RNAi) screen identifies system A neutral amino acid transporter 2 (SNAT2) as a mediator of arsenic-induced endoplasmic reticulum stress. The Journal of biological chemistry 29 22215663
2007 The sodium-coupled neutral amino acid transporter SNAT2 mediates an anion leak conductance that is differentially inhibited by transported substrates. Biophysical journal 29 17237199
2005 SNAT2 silencing prevents the osmotic induction of transport system A and hinders cell recovery from hypertonic stress. FEBS letters 28 15922329
2001 Differential influence of cAMP on the expression of the three subtypes (ATA1, ATA2, and ATA3) of the amino acid transport system A. FEBS letters 28 11566196
2018 Effects of Sodium and Amino Acid Substrate Availability upon the Expression and Stability of the SNAT2 (SLC38A2) Amino Acid Transporter. Frontiers in pharmacology 27 29467657
2009 A conserved Na(+) binding site of the sodium-coupled neutral amino acid transporter 2 (SNAT2). The Journal of biological chemistry 27 19589777
2005 Functional expression and adaptive regulation of Na+ -dependent neutral amino acid transporter SNAT2/ATA2 in normal human astrocytes under amino acid starved condition. Neuroscience letters 26 15774260
2002 The mechanism for transcriptional activation of the human ATA2 transporter gene by amino acid deprivation is different than that for asparagine synthetase. The Journal of nutrition 26 12368390
2008 Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino acids 25 18330498
2023 Single-cell RNA sequencing reveals XBP1-SLC38A2 axis as a metabolic regulator in cytotoxic T lymphocytes in multiple myeloma. Cancer letters 23 37054944
2008 Highly conserved asparagine 82 controls the interaction of Na+ with the sodium-coupled neutral amino acid transporter SNAT2. The Journal of biological chemistry 22 18319257
2014 System A amino acid transporter SNAT2 shows subtype-specific affinity for betaine and hyperosmotic inducibility in placental trophoblasts. Biochimica et biophysica acta 21 24434061
2024 miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2. Cancer biology & therapy 19 38390840
2015 Prolactin and the dietary protein/carbohydrate ratio regulate the expression of SNAT2 amino acid transporter in the mammary gland during lactation. Biochimica et biophysica acta 19 25701231
2015 Characterization and Regulation of the Amino Acid Transporter SNAT2 in the Small Intestine of Piglets. PloS one 19 26107628
2011 Promoter characterization and role of CRE in the basal transcription of the rat SNAT2 gene. American journal of physiology. Endocrinology and metabolism 18 21386061
2008 Selective tonicity-induced expression of the neutral amino-acid transporter SNAT2 in oligodendrocytes in rat brain following systemic hypertonicity. Neuroscience 18 18358621
2023 Neutral amino acid transporter SLC38A2 protects renal medulla from hyperosmolarity-induced ferroptosis. eLife 17 36722887
2013 Time-dependent expression of SNAT2 mRNA in the contused skeletal muscle of rats: a possible marker for wound age estimation. Forensic science, medicine, and pathology 17 24045877
2024 UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer. The Journal of clinical investigation 16 38949026
2015 Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity. The Journal of biological chemistry 15 26041779
2014 Transcriptional regulation of the sodium-coupled neutral amino acid transporter (SNAT2) by 17β-estradiol. Proceedings of the National Academy of Sciences of the United States of America 15 25056967
2022 SLC38A2 provides proline and alanine to regulate postnatal bone mass accrual in mice. Frontiers in physiology 14 36213239
2017 Recovery of gold from industrial wastewater by extracellular proteins obtained from a thermophilic bacterium Tepidimonas fonticaldi AT-A2. Bioresource technology 11 28521225
2011 The C-terminal domain of the neutral amino acid transporter SNAT2 regulates transport activity through voltage-dependent processes. The Biochemical journal 11 21158741
2022 Nardosinone regulates the slc38a2 gene to alleviate Parkinson's symptoms in rats through the GABAergic synaptic and cAMP pathways. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 10 35728354
2021 SNAT2/SLC38A2 Confers the Stemness of Gastric Cancer Cells via Regulating Glutamine Level. Digestive diseases and sciences 10 34173116
2019 CDK7 is a component of the integrated stress response regulating SNAT2 (SLC38A2)/System A adaptation in response to cellular amino acid deprivation. Biochimica et biophysica acta. Molecular cell research 10 30857869
2018 Membrane topology of rat sodium-coupled neutral amino acid transporter 2 (SNAT2). Biochimica et biophysica acta. Biomembranes 10 29678469
2023 Hsa_circRNA_001859 regulates pancreatic cancer progression and epithelial-mesenchymal transition through the miR-21-5p/SLC38A2 pathway. Cancer biomarkers : section A of Disease markers 7 37005877
2014 Toxoplasma gondii is dependent on glutamine and alters migratory profile of infected host bone marrow derived immune cells through SNAT2 and CXCR4 pathways. PloS one 7 25299045
2002 ATA2-mediated amino acid uptake following partial hepatectomy is regulated by redistribution to the plasma membrane. Archives of biochemistry and biophysics 7 12054432
2022 SNAT2 is responsible for hyperosmotic induced sarcosine and glycine uptake in human prostate PC-3 cells. Pflugers Archiv : European journal of physiology 6 36175560
2020 ChREBP downregulates SNAT2 amino acid transporter expression through interactions with SMRT in response to a high-carbohydrate diet. American journal of physiology. Endocrinology and metabolism 6 33225719
2011 Expression of the SNAT2 amino acid transporter during the development of rat cerebral cortex. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 6 21718781
2022 Effects of the SLC38A2-mTOR Pathway Involved in Regulating the Different Compositions of Dietary Essential Amino Acids-Lysine and Methionine on Growth and Muscle Quality in Rabbits. Animals : an open access journal from MDPI 5 36496929
2025 Epigenetic Activation of PTCD3 Promotes CRC Glutamine Metabolism and Metastasis via IGF2BP2-Mediated SLC38A2 m6A Modification. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 4 40304977
2023 CHOP upregulation and dysregulation of the mature form of the SNAT2 amino acid transporter in the placentas from small for gestational age newborns. Cell communication and signaling : CCS 4 37957724
2023 The NERP-4-SNAT2 axis regulates pancreatic β-cell maintenance and function. Nature communications 4 38071217
2021 Enhanced small neutral but not branched chain amino acid transport after epigenetic sodium coupled neutral amino acid transporter-2 (SNAT2) cDNA expression in myoblasts. Journal of cachexia, sarcopenia and muscle 4 33982880
2016 Identification of a Disulfide Bridge in Sodium-Coupled Neutral Amino Acid Transporter 2(SNAT2) by Chemical Modification. PloS one 4 27355203
2025 Upregulations of SNAT2 and GLS-1 Are Key Osmoregulatory Responses of Human Corneal Epithelial Cells to Hyperosmotic Stress. Journal of proteome research 3 40360154
2024 SNAT2-mediated regulation of estrogen and progesterone in the proliferation of goat mammary epithelial cells. Amino acids 3 38393495
2024 SLC38A2 promotes cell proliferation and invasion by promoting glutamine metabolism in adenomyosis. Experimental and therapeutic medicine 3 38590564
2020 G ATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus. PloS one 3 33201916
2021 Low pH up-regulates interleukin-6 mRNA in L6-G8C5 rat skeletal muscle cells independent of pH sensing by SNAT2(SLC38A2) transporters. FASEB bioAdvances 2 35141477
2026 Upregulation of SLC38A2 by melatonin attenuates hippocampal ferroptosis in Alzheimer's disease. Alzheimer's research & therapy 1 41715163
2025 Metabolomics analysis of SNAT2-deficient cells: Implications for the discovery of selective small-molecule inhibitors of an amino acid transporter. The Journal of biological chemistry 1 40716744
2025 Inhibiting SLC38A2 lowers blood pressure in rodent models of hypertension. Science translational medicine 1 40901922
2025 Structural and Functional Features of Melatonin Biosynthesis Genes SNAT1 and SNAT2 in Tomato and Garlic Plants. Doklady. Biochemistry and biophysics 1 41329272
2024 Bacterial over-production of the functionally active human SLC38A2 (SNAT2) exploiting the mistic tag: a cheap and fast tool for testing ligands. Molecular biology reports 1 38393484
2024 CircTSN promotes the proliferation and metastasis of gastric cancer through the miR-1825/SLC38A2 signaling axis. Discover oncology 1 39379756
2026 Metabolic engineering of SLC38A2 reprograms glutamine utilization and enhances CAR-macrophage antitumor function in solid tumors. Cancer biology & medicine 0 41925028
2026 PCK2 Promotes Non-Small Cell Lung Cancer Progression via SLC38A2- Mediated Glutamine Uptake and mTORC1 Activation. Current cancer drug targets 0 42083537
2026 The Functional Amino Acid l-Proline Enhances Lactation Performance by Activating the SNAT2-P4HA2-mTORC1 Axis. Journal of agricultural and food chemistry 0 42126009
2025 Panoramic analysis of the biological function and clinical value of SLC38A2 in human cancers: a study based on pan-cancer and single-cell analysis. Frontiers in genetics 0 41040664
2025 ALDH2 deficiency aggravates vascular injury-induced restenosis by enhancing vascular smooth muscle cell proliferation through SLC38A2-mediated upregulation of glutamine uptake. Metabolism: clinical and experimental 0 41067488
2020 Dexamethasone acutely suppresses the anabolic SNAT2/SLC38A2 amino acid transporter protein in L6-G8C5 rat skeletal muscle cells. FASEB bioAdvances 0 33490882

Missed literature

Know a paper Affinage missed for SLC38A2? Flag it for the maintainers and the community.

No submissions yet.