Affinage

SLC38A2

Sodium-coupled neutral amino acid symporter 2 · UniProt Q96QD8

Round 2 corrected
Length
506 aa
Mass
56.0 kDa
Annotated
2026-04-28
130 papers in source corpus 50 papers cited in narrative 49 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC38A2 (SNAT2) is a ubiquitously expressed, Na+-coupled neutral amino acid symporter that mediates concentrative uptake of glutamine, alanine, proline, glycine, betaine, and sarcosine with 1:1 Na+:amino acid stoichiometry, and whose transport mechanism depends on conserved Na+-coordinating residues Asn82 (TMD1) and Thr384 (TMD8), a C-terminal domain that governs voltage-dependence, and a histidine (H504) that confers pH sensitivity (PMID:10747860, PMID:18319257, PMID:19589777, PMID:21158741, PMID:16629640). Plasma membrane abundance of SNAT2 is dynamically regulated by insulin-stimulated exocytosis from trans-Golgi network compartments, Nedd4-2- and RNF5-mediated ubiquitination at N-terminal lysyl residues, and substrate-induced protein stabilization, while its transcription is induced during amino acid deprivation through an ATF4/C/EBP intronic enhancer requiring eIF2α phosphorylation and CDK7 activity, and by IL-6/STAT3, HIF-1α, and ERα pathways (PMID:17050538, PMID:17003038, PMID:25653282, PMID:16445384, PMID:16621798, PMID:30857869, PMID:19741197, PMID:31152137, PMID:25056967). SNAT2 functions as a transceptor that represses its own transcription when amino acids are sufficient, and by supplying glutamine it sustains mTORC1 signalling, drives leucine exchange, protects renal medullary cells from ferroptosis, enables cDC1-mediated anti-tumour immunity via FLCN/TFEB, provides proline for osteoblast differentiation and bone formation, and supports β-cell insulin secretion in response to the peptide NERP-4 (PMID:17488712, PMID:17429052, PMID:36722887, PMID:37407815, PMID:35261338, PMID:38071217). Placenta-specific Slc38a2 knockdown in mice directly causes fetal growth restriction, establishing a causal role in nutrient supply to the fetus (PMID:34406367).

Mechanistic history

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

    Identification of the molecular entity responsible for System A amino acid transport activity resolved a decades-old pharmacological classification into a cloned gene product, establishing SNAT2 as a ubiquitous Na+-dependent neutral amino acid symporter with defined substrate specificity and 1:1 stoichiometry.

    Evidence Heterologous expression in mammalian cells and Xenopus oocytes with electrophysiology and substrate profiling

    PMID:10747860 PMID:10930503

    Open questions at the time
    • No structural model at the time
    • Li+ intolerance mechanism unexplained
    • Tissue-specific functional roles undefined
  2. 2001 High

    Demonstration that amino acid deprivation adaptively up-regulates SNAT2 mRNA and protein, with substrate-specific transcriptional feedback, established the paradigm that SNAT2 expression is autoregulated by its own transport substrates.

    Evidence Northern blotting, Western blotting, subcellular fractionation, and transport assays in fibroblasts, myotubes, and adipocytes

    PMID:11172802 PMID:11311116

    Open questions at the time
    • Cis-regulatory elements mediating the adaptive response unknown
    • Whether the protein itself senses substrate or a downstream metabolite is unclear
  3. 2002 High

    Discovery that insulin recruits SNAT2 from intracellular endosomal stores to the plasma membrane via PI3K established a post-translational trafficking mechanism for rapid regulation of amino acid uptake, analogous to but distinct from GLUT4 translocation.

    Evidence Cell surface biotinylation, wortmannin and chloroquine inhibition, and transport assays in L6 myotubes and hepatocytes after partial hepatectomy

    PMID:11834730 PMID:12054432

    Open questions at the time
    • SNARE machinery and vesicle identity not defined
    • Whether insulin and starvation signals converge on the same SNAT2 pool unknown
  4. 2006 High

    Mapping the intronic amino acid response element (bound by ATF4 and C/EBP family members), identifying the 5′-UTR IRES enabling cap-independent translation during eIF2α phosphorylation, and showing Nedd4-2-mediated ubiquitination controls surface SNAT2, together defined the multi-layered transcriptional, translational, and post-translational regulatory logic of the adaptive response.

    Evidence ChIP, EMSA, reporter assays, IRES cell-free translation, eIF2α mutant cells, Nedd4-2 RNAi and ubiquitination assays across multiple cell types and Xenopus oocytes

    PMID:16445384 PMID:16621798 PMID:17003038

    Open questions at the time
    • Chromatin-level regulation (histone modifications) not fully dissected
    • Structural basis of Nedd4-2/SNAT2 interaction unknown
    • Whether IRES activity is regulated by RNA-binding proteins undetermined
  5. 2006 High

    Identification of key residues governing SNAT2 biophysics — H304 separating transport from anion leak, H504 mediating pH-sensitivity through allosteric Na+ binding modulation — established the first structure–function framework for the transporter.

    Evidence Site-directed mutagenesis (H304A, H504A) with two-electrode voltage clamp and DEPC chemical modification in Xenopus oocytes

    PMID:16629640 PMID:17237199

    Open questions at the time
    • High-resolution structure unavailable
    • Full anion permeation pathway not mapped
    • Whether anion leak has physiological relevance unclear
  6. 2007 High

    Establishing that SNAT2 functions as a transceptor — repressing its own gene transcription during amino acid sufficiency through a mechanism requiring JNK signalling and a large neutral amino acid sensor — resolved how cells couple transport activity to transcriptional feedback.

    Evidence shRNA, transporter chimeras, JNK inhibitors, and intronic reporter assays in L6 myotubes

    PMID:17488712

    Open questions at the time
    • Identity of the large neutral amino acid sensor upstream of JNK not determined
    • Whether transceptor signalling involves conformational change or substrate flux is unresolved
  7. 2007 High

    Demonstration that SNAT2 inhibition depletes intracellular glutamine and, by extension, leucine (via exchange transport), thereby impairing mTORC1 signalling and increasing proteolysis, placed SNAT2 as a master regulator of amino acid-dependent anabolic signalling in muscle.

    Evidence siRNA, MeAIB competitive inhibition, metabolic acidosis, HPLC amino acid profiling, and mTOR pathway Western blotting in L6 cells

    PMID:17429052 PMID:18650482

    Open questions at the time
    • Whether SNAT2-mTORC1 coupling is direct or solely through amino acid pools unclear
    • Relative contribution of SNAT2 vs SNAT1 to mTORC1 activation not separated genetically
  8. 2008 High

    Identification of Asn82 in TMD1 as critical for Na+ coordination, with mutagenesis dramatically reducing Na+ affinity and transport, provided the first direct evidence for the Na+ binding site architecture in System A transporters.

    Evidence N82A/N82S/Y337A/R374Q mutagenesis with electrophysiology and uptake assays in Xenopus oocytes

    PMID:18319257

    Open questions at the time
    • No crystal or cryo-EM structure to validate binding site geometry
    • Contribution of water molecules to Na+ coordination unknown
  9. 2009 High

    Homology modeling to LeuT/Mhp1 predicted a conserved Na+ site formed by TMD1 and TMD8, validated by the T384A mutation that dramatically lowers Na+ affinity, completing the minimal Na+ binding site model and linking SNAT2 to the LeuT-fold superfamily.

    Evidence Homology modeling, T384A mutagenesis, and electrophysiology in Xenopus oocytes

    PMID:19589777

    Open questions at the time
    • Experimental high-resolution structure still lacking
    • Substrate binding site residues not systematically identified
  10. 2011 High

    Truncation of 13 C-terminal residues abolished transport at negative potentials while sparing it at positive potentials, establishing the extracellular C-terminal domain as a voltage sensor required for physiological transporter function.

    Evidence C-terminal truncation mutagenesis with two-electrode voltage clamp and uptake assays in Xenopus oocytes

    PMID:21158741

    Open questions at the time
    • Molecular mechanism of voltage gating by C-terminal tail not defined
    • Whether post-translational modifications of C-terminus modulate gating is unknown
  11. 2015 High

    Identification of specific N-terminal lysyl residues as ubiquitination sites mediating substrate-induced stability, and the demonstration that mTOR regulates SNAT2 surface abundance via Nedd4-2 in human IUGR placentae, integrated ubiquitin-dependent trafficking into the physiological regulation of fetal nutrient supply.

    Evidence N-terminal lysine-to-alanine mutagenesis, chimeric SNAT2-SNAT5 constructs, IUGR placental fractionation, and ubiquitination assays

    PMID:25653282 PMID:26374858

    Open questions at the time
    • Deubiquitinase(s) counteracting Nedd4-2 at SNAT2 not identified
    • Whether mTOR regulates Nedd4-2 directly or through intermediates is unclear
  12. 2018 High

    Experimental determination of SNAT2 membrane topology (11 TMDs, intracellular N-terminus, extracellular C-terminus, three verified N-glycosylation sites) resolved conflicting bioinformatic predictions and anchored the structure–function data to a validated topology model.

    Evidence mPEG-Mal chemical modification, protease cleavage, immunofluorescence, and glycosylation analysis

    PMID:29678469

    Open questions at the time
    • High-resolution 3D structure still unavailable
    • Role of individual glycosylation sites in trafficking or function not tested
  13. 2019 High

    Discovery that HIF-1α drives SNAT2 transcription under hypoxia via elements overlapping with the ERα-responsive promoter, and that SNAT2 overexpression confers endocrine resistance in breast cancer xenografts, revealed a regulatory switch enabling tumour adaptation.

    Evidence ChIP for HIF-1α and ERα, reporter assays, siRNA, and xenograft models

    PMID:31152137

    Open questions at the time
    • Whether HIF-1α and ERα compete or cooperate at the SNAT2 promoter under intermediate oxygen tensions is untested
    • Therapeutic targeting of SNAT2 in endocrine-resistant breast cancer not explored
  14. 2021 High

    Placenta-specific Slc38a2 knockdown in mice directly caused fetal growth restriction, establishing causality between reduced placental SNAT2 and impaired fetal nutrient supply, beyond the correlative IUGR associations previously observed.

    Evidence Lentiviral shRNA blastocyst transduction with placenta-specific knockdown; MeAIB uptake, fetal weight, and viability measurements

    PMID:34406367

    Open questions at the time
    • Whether Slc38a2 ablation recapitulates full IUGR syndrome or only weight restriction is unknown
    • Compensation by SNAT1 or SNAT4 not assessed
  15. 2022 High

    Conditional knockout studies established that SLC38A2 cell-autonomously supplies proline for collagen-rich protein synthesis in osteoblasts, directly controlling differentiation and bone formation, revealing a tissue-specific metabolic function beyond glutamine supply.

    Evidence Osteoblast- and Prrx1Cre-driven conditional knockouts, [13C]-proline tracing, metabolomics, micro-CT, and histomorphometry

    PMID:35261338 PMID:36213239

    Open questions at the time
    • Whether SNAT2 provides proline to other collagen-producing cell types (e.g., fibroblasts) is untested
    • Mechanism by which SNAT2-derived proline is preferentially channeled to protein synthesis vs. catabolism is unexplored
  16. 2022 High

    Identification of UBE2C-mediated monoubiquitination at K59 that blocks K63-polyubiquitination at K33, preventing EPN1-mediated endocytosis and stabilizing SNAT2 at the membrane, revealed a ubiquitin-code mechanism controlling transporter surface retention with implications for lymphangiogenesis in bladder cancer.

    Evidence Site-specific K59/K33 mutagenesis, ubiquitination assays, surface protein analysis, siRNA, xenograft/PDX models

    PMID:38949026

    Open questions at the time
    • Whether UBE2C–SNAT2 interaction is direct or requires a scaffold E3 ligase is unresolved
    • Generalizability of ubiquitin-code regulation across tissues not tested
  17. 2023 High

    Demonstration that cDC1 dendritic cells compete with tumour cells for glutamine via SLC38A2, and that SLC38A2 signals through FLCN/TFEB to license anti-tumour CD8+ T cell priming, established SLC38A2 as a critical metabolic checkpoint in tumour immunity.

    Evidence DC-specific SLC38A2 and FLCN knockout mice, in vivo tumour models, CD8+ T cell assays, intratumoral glutamine supplementation

    PMID:37407815

    Open questions at the time
    • Whether SLC38A2 signalling in other immune cells (macrophages, CD4+ T cells) similarly controls function is unexplored
    • Mechanism by which SNAT2-derived glutamine activates FLCN is undefined
  18. 2023 High

    Discovery that SLC38A2 protects renal medullary cells from hyperosmolarity-induced ferroptosis via mTORC1 activation, and that the peptide NERP-4 acts through SNAT2 to stimulate β-cell insulin secretion, expanded the physiological repertoire of SNAT2 to stress survival and endocrine function.

    Evidence Slc38a2 knockout mice with water restriction, ferroptosis markers, mTORC1 blotting; SNAT2 deletion and pharmacological inhibition with insulin secretion assays in islets and db/db mice

    PMID:36722887 PMID:38071217

    Open questions at the time
    • How NERP-4 mechanistically engages SNAT2 (direct binding vs. indirect modulation) is unresolved
    • Whether renal SNAT2 loss causes chronic kidney pathology under physiological conditions is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive functional characterization, no high-resolution experimental structure of SNAT2 exists; the structural basis for substrate selectivity, the anion leak pathway, and the transceptor signalling mechanism remain undefined at atomic resolution.
  • No cryo-EM or crystal structure of SNAT2 or any close SLC38 family member
  • Transceptor signalling mechanism (conformational vs. flux-dependent) unresolved
  • Pharmacological inhibitors with clinical utility not yet developed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 9 GO:0140299 molecular sensor activity 1
Localization
GO:0005886 plasma membrane 9 GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-382551 Transport of small molecules 9 R-HSA-162582 Signal Transduction 5 R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 2
Partners
ATF4EPN1ESR1HIF1AIGF2BP2NEDD4LRNF5UBE2C

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 SLC38A2 (ATA2/SNAT2) was cloned and characterized as the protein responsible for system A amino acid transport activity ubiquitously expressed in mammalian tissues. It mediates Na+-dependent transport of neutral amino acids (model substrate: α-(methylamino)isobutyric acid), is pH-sensitive, Li+-intolerant, and has a 1:1 Na+:amino acid stoichiometry. Heterologous expression in mammalian cells and Xenopus laevis oocytes; transport current electrophysiology; substrate specificity assays The Journal of biological chemistry High 10747860 10930503
2001 SNAT2 protein is present in plasma-membrane and internal-membrane fractions of rat skeletal muscle, adipose tissue, L6 myotubes, and 3T3-L1 adipocytes, with subcellular distribution similar to GLUT4. Chronic amino acid deprivation causes a time-dependent increase in SNAT2 protein abundance, establishing the adaptive up-regulation of System A. Subcellular fractionation; Western blotting; immunolocalization with specific polyclonal antibodies The Biochemical journal High 11311116
2001 Adaptive stimulation of System A transport upon amino acid starvation in human fibroblasts is directly correlated with increased ATA2 (SNAT2) mRNA expression; supplementation with System A substrates (but not other amino acids) suppresses both ATA2 mRNA levels and transport activity, demonstrating substrate-specific transcriptional feedback. Northern blotting; transport assays; substrate specificity competition experiments FEBS letters Medium 11172802
2002 Insulin stimulates System A transport in L6 skeletal muscle cells by recruiting SAT2 (SNAT2) to the plasma membrane from an endosomal compartment; this process requires phosphatidylinositol 3-kinase activity and is blocked by chloroquine (which impairs endosomal recycling) without affecting insulin-mediated PKB/GSK3 phosphorylation or GLUT4 translocation. Cell surface biotinylation; pharmacological inhibition (wortmannin, chloroquine); Western blotting; radiolabeled transport assays The Journal of biological chemistry High 11834730
2002 ATA2-mediated amino acid transport up-regulation following partial hepatectomy is regulated by redistribution of ATA2 protein to the plasma membrane from an intracellular compartment, not by changes in steady-state ATA2 mRNA levels. Plasma membrane isolation; Western blotting; Northern blotting Archives of biochemistry and biophysics Medium 12054432
2002 Transcriptional activation of the ATA2 (SNAT2) gene by amino acid deprivation is largely independent of de novo protein synthesis (unlike asparagine synthetase), is detectable within 2–4 h, and is not induced by glucose deprivation, indicating a distinct genomic regulatory mechanism. Reporter gene assays; Northern blotting; cycloheximide/actinomycin D inhibition; HepG2 cells The Journal of nutrition Medium 12368390
2004 De novo synthesis of new SNAT2 transporter protein is essential for the hypertonic stimulation of System A transport activity in human fibroblasts; transcription inhibition (DRB) abolishes the hypertonic transport increase, whereas the adaptive increase induced by amino acid starvation only partly requires new SNAT2 synthesis. Biotinylation of surface proteins; Western blotting; immunocytochemistry; transcription inhibitor (DRB) experiments Biochimica et biophysica acta Medium 15581851
2005 siRNA-mediated silencing of SNAT2 in hypertonically stressed human fibroblasts prevents the increase in System A transport activity, blocks expansion of the intracellular amino acid pool, and markedly delays cell volume recovery, demonstrating that SNAT2 induction is required for regulatory volume increase (RVI). siRNA knockdown; radiolabeled transport assays; intracellular amino acid measurement; cell volume measurement FEBS letters High 15922329
2006 The amino acid response element driving SNAT2 up-regulation upon amino acid limitation resides in the first intron of the gene; ATF and C/EBP family transcription factors bind this intronic enhancer in vitro and in vivo (ChIP), with specific members acting as activators or repressors, and amino acid deprivation increases RNA polymerase II recruitment to the SNAT2 promoter. Deletion/reporter assays; ChIP; EMSA; transcription factor overexpression The Biochemical journal High 16445384
2006 SNAT2 induction by amino acid starvation requires eIF2α phosphorylation and involves an internal ribosome entry site (IRES) in the 5'-UTR that enables cap-independent translation, as well as increased gene transcription; hypertonic stress induction of SNAT2, by contrast, is eIF2α phosphorylation-independent. eIF2α phosphorylation-deficient mutant cells; IRES reporter assays; cell-free translation; Northern/Western blotting The Journal of biological chemistry High 16621798
2006 SNAT2 transporter function is associated with a leak anion conductance that does not require substrate transport; transported substrates (L-alanine, L-glutamine, MeAIB) inhibit this anion leak with different potencies. Mutation H304A eliminates alanine transport but retains anion leak current, and the selectivity sequence of the anion conductance was determined. Electrophysiology (whole-cell patch clamp and two-electrode voltage clamp) in Xenopus oocytes; site-directed mutagenesis (H304A); ion substitution experiments Biophysical journal High 17237199
2006 A conserved C-terminal histidine residue (H504 in SNAT2, H471 in SNAT5) mediates the pH-sensitivity of System A and N transporters through an allosteric mechanism influencing Na+ binding; DEPC modification abolishes pH-sensitivity and its effects are reversed by hydroxylamine and blocked by substrate; H504A mutation produces reduced, DEPC-resistant pH-sensitivity without changing Na+ affinity at low pH. Xenopus oocyte expression; site-directed mutagenesis (H504A); DEPC chemical modification; transport current electrophysiology; Na+ affinity measurement The Biochemical journal High 16629640
2006 Ubiquitin ligase Nedd4-2 regulates SNAT2 (ATA2) surface abundance by polyubiquitinating the transporter at the plasma membrane, leading to endocytotic sequestration and proteasomal degradation; Nedd4-2 RNAi increases SNAT2 activity with concomitant decreased polyubiquitination; catalytically inactive Nedd4-2 has no effect. Xenopus oocyte expression; transfection in CHO cells and adipocytes; RNAi; co-localization by immunofluorescence; proteasome inhibitor (MG132); ubiquitination assays The Journal of biological chemistry High 17003038
2006 ATA2 (SNAT2) is stored in a trans-Golgi network (TGN) compartment (co-localizing with syntaxin 6, not EEA1) in adipocytes; insulin stimulus releases SNAT2-containing vesicles from the TGN to the plasma membrane through a pathway distinct from GLUT4 translocation; brefeldin A (TGN exit inhibitor) preferentially blocks insulin-stimulated MeAIB uptake over glucose transport. Live-cell imaging of EGFP-tagged ATA2; immunofluorescence co-localization; brefeldin A inhibition; insulin-stimulated transport assays in 3T3-L1 adipocytes The Journal of biological chemistry High 17050538
2007 Two distinct amino acid sensor/effector pathways control SNAT2 expression: (1) JNK activation during amino acid withdrawal induces SNAT2 transcription via an intronic nutrient-sensitive domain; (2) a sensor for large neutral amino acids (Tyr, Gln) inhibits JNK and suppresses SNAT2 up-regulation. Additionally, SNAT2 itself provides a repressive signal for its own gene transcription when amino acids are sufficient, consistent with a transceptor (transporter-receptor) function. shRNA; transporter chimera expression; JNK pathway inhibitors; intronic reporter assays; SNAT2 protein stability measurements in L6 myotubes The Journal of biological chemistry High 17488712
2007 Selective inhibition of SNAT2 (by MeAIB, metabolic acidosis at pH 7.1, or siRNA knockdown) depletes intracellular L-Gln and indirectly depletes leucine and other amino acids maintained by the L-Gln gradient, strongly impairing mTOR signalling to S6K, S6, and 4E-BP1 and reducing protein synthesis in L6 skeletal muscle cells. siRNA; competitive substrate inhibition (MeAIB); metabolic acidosis; amino acid HPLC; mTOR pathway Western blotting; protein synthesis assays Journal of the American Society of Nephrology : JASN High 17429052
2008 SNAT2 inhibition by metabolic acidosis (pH 7.1) or MeAIB stimulates proteolysis in L6 myotubes; this effect is mediated through both mTOR and PI3K signalling pathways, and SNAT2 partial silencing impairs insulin signalling through PI3K, linking SNAT2-mediated glutamine uptake to regulation of muscle proteolysis and insulin resistance. siRNA; MeAIB competitive inhibition; proteasome inhibitor; mTOR/PI3K pharmacological inhibitors; proteolysis assays in L6 cells Journal of the American Society of Nephrology : JASN High 18650482
2008 In glutamatergic neurons, SAT2 (SNAT2) is predominantly targeted to somatodendritic compartments and supplies glutamine for conversion to glutamate required for retrograde dendritic signalling; MeAIB inhibition of SAT2 reduces neuronal glutamine uptake, lowers intracellular glutamate, and suppresses inhibitory synaptic inputs to pyramidal cells from fast-spiking interneurons. Immunohistochemistry; confocal microscopy; electron microscopy; in vivo electrical stimulation; in vitro depolarization; MeAIB pharmacological inhibition; electrophysiology of neocortical circuits Cerebral cortex (New York, N.Y. : 1991) High 18832333
2008 Asparagine 82 in transmembrane domain 1 of SNAT2 is critical for Na+ coordination; N82A mutation virtually eliminates alanine transport current and amino acid uptake, dramatically reduces Na+ affinity (K(Na+)), and increases apparent Km for alanine 27-fold, demonstrating a direct or indirect role of Asn82 in Na+ binding. Site-directed mutagenesis (N82A, N82S, Y337A, R374Q); Xenopus oocyte expression; two-electrode voltage clamp; radiolabeled amino acid uptake assays The Journal of biological chemistry High 18319257
2008 Despite increased ATF4 binding to the C/EBP-ATF composite site in the SNAT2 gene during unfolded protein response (UPR) activation, SNAT2 transcription is not enhanced in HepG2 cells; UPR suppresses the amino acid response (AAR)-induced increase in SNAT2 transcription, demonstrating that the UPR generates a repressive signal downstream of ATF4 binding that is chromatin-level (lacking histone H3 hyperacetylation and general transcription factor recruitment at the promoter). ChIP (H3 acetylation, RNA Pol II, general transcription factors); reporter gene assays; pharmacological UPR/AAR activation; 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, predicted by homology modeling to LeuT/Mhp1 structures; the T384A mutation in the predicted TMD8 Na+ binding site dramatically lowers Na+ affinity and inhibits the anion leak current, consistent with a cation binding site conserved across SLC38 and related bacterial transporter families. Profile-based sequence analysis; homology modeling (LeuT, Mhp1 templates); site-directed mutagenesis (T384A); Xenopus oocyte expression; electrophysiology; Na+ affinity measurement The Journal of biological chemistry High 19589777
2009 In neocortical neurons, SNAT2 expression is constitutively low but potently induced by depletion of neutral amino acids; substrates of the SLC6 GABA transporter family (taurine, GABA, β-alanine) repress SNAT2 expression more potently (~10×) than System A substrates; ATF4 and C/EBP induction by amino acid deprivation mediates SNAT2 transcriptional regulation in neurons. Neuronal culture; SNAT2 de novo induction; electrophysiology (spontaneous excitatory activity); ATF4/C/EBP Western blotting; pharmacological substrate competition The Journal of biological chemistry Medium 19240036
2009 IL-6 stimulates System A amino acid transporter activity in human trophoblast cells through STAT3-dependent transcriptional up-regulation of SNAT2 mRNA and protein; siRNA targeting STAT3 reduces SNAT2 (but not SNAT1) expression and abolishes IL-6-stimulated System A activity. TNF-α also stimulates system A via SNAT2 but through a JAK/STAT-independent pathway. siRNA (STAT3); Western blotting; RT-PCR; radiolabeled MeAIB transport assays; phospho-STAT3 detection in primary human trophoblasts American journal of physiology. Cell physiology High 19741197
2011 Chronic competitive inhibition of SNAT2 with MeAIB reduces cell proliferation and depletes intracellular SNAT2 substrate amino acids as well as leucine; surprisingly, Me-AIB elevates mTOR-dependent p70S6K1 phosphorylation despite amino acid pool depletion. Proteomic analysis of TAP-purified SNAT2 fusion proteins identified two novel SNAT2-interacting proteins potentially involved in signalling for protein turnover and cell growth. Competitive inhibition (MeAIB); mTOR pathway Western blotting; TAP-tag purification + proteomics; cell proliferation/size assays in MCF-7 cells Frontiers in bioscience (Elite edition) Medium 21622135
2011 C-terminal domain deletion of SNAT2 (13 residues) abolishes amino acid transport at negative membrane potentials while allowing transport at positive potentials; the truncation increases apparent affinity for alanine (~3-fold) and Na+ (~2-fold) without affecting surface expression, demonstrating that the C-terminal extracellular domain acts as a voltage regulator required for normal amino acid translocation at physiological potentials. C-terminal truncation mutagenesis; Xenopus oocyte expression; two-electrode voltage clamp; radiolabeled amino acid uptake; surface expression assays The Biochemical journal High 21158741
2011 SNAT2 is the primary transporter mediating L-proline uptake by embryonic stem (ES) cells; uptake of L-proline through SNAT2 is required for ES cell differentiation to early primitive ectoderm-like cells, as SNAT2 substrate competitors (but not non-substrates) block morphological changes, gene expression changes, and differentiation kinetics. Competitive substrate inhibition; transport assays; morphological and gene expression differentiation assays in ES cells American journal of physiology. Cell physiology Medium 21346154
2012 A genome-wide RNAi screen identified SNAT2 as required for arsenite-induced ER stress response; arsenite up-regulates SNAT2 expression and activity in an ATF4-dependent manner; inhibition of SNAT2 expression/activity or glutamine deprivation specifically suppresses arsenite-induced (but not tunicamycin-induced) ER stress and mTOR activation, placing SNAT2 upstream of mTOR in this pathway. Genome-wide shRNA screen; flow cytometry; SNAT2 inhibition (MeAIB, siRNA); mTOR pathway Western blotting; ER stress reporters The Journal of biological chemistry High 22215663
2013 SNAT2 transports the PET radiotracer anti-[18F]FACBC with Michaelis-Menten kinetics (Km ~197 μM), lower affinity than ASCT2 (Km ~97 μM); characterized in Xenopus oocytes expressing human SNAT2. Xenopus oocyte expression; radiolabeled [14C]FACBC kinetic uptake assays Nuclear medicine and biology Medium 23647854
2014 Only SNAT2 (among SNAT1, 2, and 4) exhibits betaine uptake activity; human and rat SNAT2 transport betaine with Km values of 5.3 mM and 4.6 mM, respectively; betaine exclusively inhibits SNAT2 among the system A subtypes; hypertonicity preferentially induces SNAT2 expression and its plasma membrane targeting in placental trophoblasts. Transfection in HEK293 cells; [14C]betaine uptake assays; Western blotting of plasma membrane fractions; immunocytochemistry; RT-PCR in TR-TBT 18d-1 cells Biochimica et biophysica acta High 24434061
2014 17β-estradiol regulates SNAT2 transcription through a functional estrogen response element (ERE) in the SNAT2 promoter bound by estrogen receptor α (ERα); in vivo ChIP shows progressive ERα binding to the SNAT2 promoter during gestation correlating with estradiol levels; the ERα-ERE complex also contains PARP1, Ku70, and GAPDH, and silencing each abolishes estradiol-stimulated SNAT2 promoter activity. Reporter assays; EMSA; supershift assays; in vivo ChIP; LC-MS proteomics of ERα-ERE complex; Western blotting; ERE deletion/mutation Proceedings of the National Academy of Sciences of the United States of America High 25056967
2015 RNF5 ubiquitin ligase associates with, ubiquitinates, and promotes degradation of SLC38A2 (along with SLC1A5) in response to paclitaxel-induced ER stress in breast cancer cells, decreasing glutamine uptake, TCA cycle components, and mTOR signalling while increasing autophagy and cell death. Co-immunoprecipitation; ubiquitination assays; siRNA knockdown; metabolic profiling; mTOR pathway Western blotting; cell death/autophagy assays Cancer cell High 25759021
2015 SNAT2 protein stability is regulated by the ubiquitin-proteasome system via N-terminal lysyl residues; linoleic acid (LOA) increases ubiquitination and proteasomal degradation of SNAT2 through increased Nedd4.2 expression; mutation of seven N-terminal lysyl residues to alanine protects SNAT2 from LOA-induced degradation; the N-terminal cytoplasmic tail confers substrate-induced changes in SNAT2 stability when grafted onto SNAT5. Proteasome inhibitor; shRNA (Nedd4.2); N-terminal lysine mutagenesis; chimeric SNAT2-SNAT5 construct; transport assays; Western blotting in L6 myotubes/HeLa The Journal of biological chemistry High 25653282
2015 Decreased placental mTOR activity in IUGR is associated with increased NEDD4-2 expression (+72%), increased ubiquitination of SNAT2 (+180%), and decreased SNAT2 protein in the syncytiotrophoblast microvillous plasma membrane (–31%), establishing that mTOR regulates placental SNAT2 surface trafficking via the ubiquitin pathway. Western blotting (mTORC1/2 activity, NEDD4-2, SNAT2); ubiquitination assays; plasma membrane fractionation; radiolabeled MeAIB transport in human IUGR placental tissue Clinical science (London, England : 1979) High 26374858
2015 Hyperosmotic stress coordinates SNAT2 induction with GADD34 up-regulation; increased GADD34 (a PP1 regulatory subunit) dephosphorylates eIF2α, enhancing SNAT2-mediated amino acid uptake; GADD34 induction during osmotic stress depends on c-Jun/CRE-mediated transcription and mRNA stabilization (not ATF4, unlike other stresses), establishing a SNAT2/GADD34 axis for cell survival. Reporter assays (CRE); mRNA stability assays; eIF2α phosphorylation Western blotting; SNAT2 transport assays; GADD34 overexpression/knockdown The Journal of biological chemistry High 26041779
2016 Net glutamine uptake in HeLa and 143B cancer cells does not depend on ASCT2 but requires SNAT1 and SNAT2; ASCT2 deletion causes amino acid starvation response and SNAT1 up-regulation to functionally replace ASCT2; SNAT2-mediated net uptake is essential for maintaining intracellular glutamine for glutaminolysis. CRISPR/Cas9 knockout (ASCT2); siRNA (GCN2, SNAT1); radiolabeled amino acid uptake; cell growth assays; Western blotting The Journal of biological chemistry High 27129276
2018 Membrane topology of SNAT2 was experimentally determined: 11 transmembrane domains with an intracellular N-terminus and extracellular C-terminus; three N-glycosylation sites were verified at the largest extracellular loop using chemical modification (mPEG-Mal), protease cleavage assays, immunofluorescence, and glycosylation analysis. mPEG-Mal chemical modification; protease cleavage; immunofluorescence; glycosylation assays; bioinformatics Biochimica et biophysica acta. Biomembranes High 29678469
2018 Extracellular Na+ is required for the SNAT2 adaptive stress response: Na+ withdrawal during amino acid deprivation prevents SNAT2 gene induction; substrate-induced repression of SNAT2 protein stability requires the cytoplasmic N-terminal tail with lysyl residues; grafting this tail onto SNAT5 confers substrate-induced stability changes, while mutation of N-terminal lysines renders SNAT2 stable and insensitive to substrate. Na+ substitution; N-terminal chimeric SNAT2/SNAT5 constructs; lysine-to-alanine mutagenesis; Western blotting; transport assays in HeLa cells Frontiers in pharmacology High 29467657
2019 Hypoxia induces SNAT2 expression in breast cancer primarily through HIF-1α (rather than ERα, which dominates under normoxia); HIF-1α and ERα binding sites overlap in SNAT2 cis-regulatory elements; fulvestrant (ER antagonist) cannot suppress SNAT2 under hypoxia; SNAT2 overexpression causes complete endocrine resistance in vivo. ChIP (HIF-1α, ERα); reporter assays; siRNA; xenograft mouse model; Western blotting; in vitro/in vivo growth assays Proceedings of the National Academy of Sciences of the United States of America High 31152137
2019 CDK7 activity is upregulated during amino acid deprivation in a GCN2-dependent manner and is required for the SNAT2 adaptive stress response; CDK7 inhibition (THZ-1) attenuates ATF4 induction and blocks System A adaptation; drug-resistant CDK7 expression mitigates THZ-1 effects, establishing CDK7 as a component of the integrated stress response regulating SNAT2. Pharmacological CDK inhibitors (THZ-1, roscovitine, flavopiridol); doxycycline-inducible drug-resistant CDK7; Western blotting; System A transport assays Biochimica et biophysica acta. Molecular cell research High 30857869
2021 Placenta-specific lentiviral shRNA knockdown of Slc38a2 (59% reduction) in mice reduces near-term fetal and placental weight, fetal viability, trophoblast plasma membrane SNAT2 protein, and placental System A transport activity (MeAIB uptake), directly demonstrating that placental Slc38a2 deficiency causes fetal growth restriction. Lentiviral shRNA blastocyst transduction (placenta-specific KD); radiolabeled MeAIB uptake; Western blotting; fetal weight measurements Clinical science (London, England : 1979) High 34406367
2022 SLC38A2 acts cell-autonomously in osteoblasts to provide proline (and alanine) for the synthesis of proline-rich osteoblast proteins (RUNX2, OSX, OCN, COL1A1); genetic ablation of SLC38A2 in osteoblasts impairs osteoblast differentiation and bone formation in mice; metabolomics showed proline is primarily incorporated into nascent protein rather than metabolized. Conditional genetic knockout (osteoblast-specific); metabolomics; bone histomorphometry; differentiation assays; [13C]-proline tracing eLife High 35261338
2022 SLC38A2 provides proline and alanine to osteoblast lineage cells during postnatal bone homeostasis; Prrx1Cre-driven SLC38A2 ablation decreases bone mass in both sexes by reducing osteoblast numbers, impairing proliferation and osteogenic differentiation of skeletal stem and progenitor cells. Conditional knockout (Prrx1Cre); micro-CT; histomorphometry; cell proliferation and differentiation assays; amino acid uptake measurements Frontiers in physiology High 36213239
2022 UBE2C mediates monoubiquitination of SNAT2 at lysine 59, which inhibits K63-linked polyubiquitination at lysine 33; this crosstalk between ubiquitination types increases SNAT2 membrane protein levels by suppressing EPN1-mediated endocytosis; elevated membrane SNAT2 facilitates glutamine uptake and metabolism to promote VEGFC secretion and lymphangiogenesis in bladder cancer. Co-IP; ubiquitination assays (site-specific mutagenesis K59, K33); cell surface protein assays; siRNA; xenograft/PDX models; VEGFC ELISA; lymphangiogenesis assays The Journal of clinical investigation High 38949026
2022 SNAT2 is responsible for hyperosmotic stress-induced uptake of sarcosine and glycine in PC-3 prostate cancer cells; siRNA knockdown of SNAT2 reduces Vmax of sarcosine uptake by ~80% without altering Km, and SNAT2 is up-regulated at mRNA and protein levels under hyperosmotic conditions, identifying sarcosine as a novel SNAT2 substrate. siRNA; radiolabeled sarcosine/glycine uptake kinetics; RT-PCR; Western blotting; hyperosmotic cell culture Pflugers Archiv : European journal of physiology Medium 36175560
2023 Tumour cells and cDC1 dendritic cells compete for glutamine uptake via SLC38A2; glutamine signalling through SLC38A2 in cDC1s activates FLCN, which impinges on TFEB function to license cDC1 activation of CD8+ T cells; SLC38A2 deficiency in DCs phenocopies FLCN loss and eliminates anti-tumour therapeutic effects of glutamine supplementation. Genetic deletion (DC-specific SLC38A2 KO, FLCN KO); in vivo tumour models; CD8+ T cell priming assays; nutrient competition assays; epistasis (TFEB-dependence); intratumoral glutamine supplementation Nature High 37407815
2023 XBP1 directly binds the SLC38A2 promoter and transcriptionally represses it; SLC38A2 silencing in T cells decreases glutamine uptake and causes immune dysfunction, establishing an XBP1-SLC38A2 axis as a metabolic regulator of cytotoxic T lymphocyte function in multiple myeloma. ChIP; dual-luciferase reporter assay; siRNA (SLC38A2); glutamine uptake assay; T cell functional assays; single-cell RNA-seq Cancer letters Medium 37054944
2023 NERP-4 (a VGF-derived peptide) acts on SNAT2 to increase glutamine, alanine, and proline uptake into pancreatic β cells, stimulating insulin secretion; SNAT2 deletion and inhibition abolish NERP-4's protective effects on β-cell maintenance and function in db/db mice, defining a peptide-amino acid transporter autocrine axis. SNAT2 genetic deletion; pharmacological inhibition; amino acid uptake assays; insulin secretion assays; isolated islets; transgenic Ca2+ reporter mice; db/db mouse model Nature communications High 38071217
2023 SLC38A2 protects renal medullary collecting duct (MCD) cells from hyperosmolarity-induced ferroptosis; SLC38A2 overexpression attenuates hyperosmotic cell death while Slc38a2 deletion worsens it; the osmoprotective effect requires mTORC1 activation; Slc38a2 knockout mice exhibit increased medullary ferroptosis after water restriction in vivo. RNA-Seq; SLC38A2 overexpression/siRNA; genetic Slc38a2 knockout mice; ferroptosis markers (ROS, GSH, MDA, iron); mTORC1 Western blotting; water restriction in vivo model eLife High 36722887
2025 IGF2BP2 promotes SLC38A2 mRNA stability in an m6A-dependent manner downstream of PTCD3; PTCD3-IGF2BP2-SLC38A2 axis drives glutaminolysis and metastasis in colorectal cancer; SLC38A2 overexpression rescues proliferation/invasion defects caused by PTCD3 depletion. Co-IP; RIP; dual-luciferase assay; siRNA/overexpression; CRC xenograft model; glutamine metabolism assays FASEB journal Medium 40304977

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2019 Blood-Brain Barrier: From Physiology to Disease and Back. Physiological reviews 1645 30280653
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 Establishment and Dysfunction of the Blood-Brain Barrier. Cell 1304 26590417
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2008 Amino acid transport across mammalian intestinal and renal epithelia. Physiological reviews 657 18195088
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2015 SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 548 25561175
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2005 Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Molecular & cellular proteomics : MCP 434 15951569
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2000 Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of system A. The Journal of biological chemistry 220 10747860
2023 SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity. Nature 219 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 206 27129276
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2015 Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies. Cancer cell 194 25759021
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2020 AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System. Molecular cell 152 31995728
2015 Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef. Cell host & microbe 146 26439863
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
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) 77 26374858
2011 SNAT2 transceptor signalling via mTOR: a role in cell growth and proliferation? Frontiers in bioscience (Elite edition) 77 21622135
2008 System A transporter SAT2 mediates replenishment of dendritic glutamate pools controlling retrograde signaling by glutamate. Cerebral cortex (New York, N.Y. : 1991) 76 18832333
2001 The adaptive regulation of amino acid transport system A is associated to changes in ATA2 expression. FEBS letters 74 11172802
2001 Subcellular localization and adaptive up-regulation of the System A (SAT2) amino acid transporter in skeletal-muscle cells and adipocytes. The Biochemical journal 72 11311116
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 69 30274521
2006 The role of the neutral amino acid transporter SNAT2 in cell volume regulation. Acta physiologica (Oxford, England) 68 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
1992 Genetic relationships between southern African SAT-2 isolates of foot-and-mouth-disease virus. Epidemiology and infection 58 1334842
2016 Cloning and characterization of the serotonin N-acetyltransferase-2 gene (SNAT2) in rice (Oryza sativa). Journal of pineal research 57 27121038
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
2008 Inhibition of SNAT2 by metabolic acidosis enhances proteolysis in skeletal muscle. Journal of the American Society of Nephrology : JASN 43 18650482
2006 Amino acid transporter ATA2 is stored at the trans-Golgi network and released by insulin stimulus in adipocytes. The Journal of biological chemistry 43 17050538
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
2013 SNAT2 expression and regulation in human growth-restricted placentas. Pediatric research 37 23728383
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 36 16629640
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 31 36210829
2025 KAT2A-mediated H3K79 succinylation promotes ferroptosis in diabetic nephropathy by regulating SAT2. Life sciences 30 40409584
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 Complementary expression of SN1 and SAT2 in the islets of Langerhans suggests concerted action of glutamine transport in the regulation of insulin secretion. Biochemical and biophysical research communications 27 19233140
2009 A conserved Na(+) binding site of the sodium-coupled neutral amino acid transporter 2 (SNAT2). The Journal of biological chemistry 26 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 22 37054944
2012 Cancer-linked satellite 2 DNA hypomethylation does not regulate Sat2 non-coding RNA expression and is initiated by heat shock pathway activation. Epigenetics 22 22722874
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 20 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
2018 Chimeric O1K foot-and-mouth disease virus with SAT2 outer capsid as an FMD vaccine candidate. Scientific reports 17 30209254
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
2019 Phylogeographical and cross-species transmission dynamics of SAT1 and SAT2 foot-and-mouth disease virus in Eastern Africa. Molecular ecology 15 31074125
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
2007 Study of the genetic heterogeneity of SAT-2 foot-and-mouth disease virus in sub-Saharan Africa with specific focus on East Africa. The Onderstepoort journal of veterinary research 15 18453238
2024 UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer. The Journal of clinical investigation 14 38949026
2022 SLC38A2 provides proline and alanine to regulate postnatal bone mass accrual in mice. Frontiers in physiology 14 36213239
2023 B and T Cell Epitopes of the Incursionary Foot-and-Mouth Disease Virus Serotype SAT2 for Vaccine Development. Viruses 13 36992505
2022 SAT2 regulates Sertoli cell-germline interactions via STIM1-mediated ROS/WNT/β-catenin signaling pathway. Cell biology international 13 35819096
2018 Streptothricin acetyl transferase 2 (Sat2): A dominant selection marker for Caenorhabditis elegans genome editing. PloS one 13 29742140
2014 Determining the epitope dominance on the capsid of a serotype SAT2 foot-and-mouth disease virus by mutational analyses. Journal of virology 13 24829347
2019 Inherent biophysical stability of foot-and-mouth disease SAT1, SAT2 and SAT3 viruses. Virus research 12 30807778
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
2020 Meta-analysis of Genetic Diversity of the VP1 Gene Among the Circulating O, A, and SAT2 Serotypes and Vaccine Strains of FMD Virus in Egypt. Journal of veterinary research 10 33367136
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
2017 Evaluation of immune responses of stabilised SAT2 antigens of foot-and-mouth disease in cattle. Vaccine 10 28431813
2012 Mapping of antigenic determinants on a SAT2 foot-and-mouth disease virus using chicken single-chain antibody fragments. Virus research 9 22698877
2021 Efficacy of SAT2 Foot-and-Mouth Disease Vaccines Formulated with Montanide ISA 206B and Quil-A Saponin Adjuvants. Vaccines 8 34579233
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
2008 Molecular characterization of SAT-2 foot-and-mouth disease virus isolates obtained from cattle during a four-month period in 2001 in Limpopo Province, South Africa. The Onderstepoort journal of veterinary research 7 19294983
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 Viral Population Diversity during Co-Infection of Foot-And-Mouth Disease Virus Serotypes SAT1 and SAT2 in African Buffalo in Kenya. Viruses 6 35632639
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
2020 Production of foot-and-mouth disease virus SAT2 VP1 protein. AMB Express 5 31912326
2017 Increased Sat2 expression is associated with busulfan-induced testicular Sertoli cell injury. Toxicology in vitro : an international journal published in association with BIBRA 5 28578006
2015 Evaluation of Spirulina platensis extract as natural antivirus against foot and mouth disease virus strains (A, O, SAT2). Veterinary world 5 27047027
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
2006 Evaluation of SAT-1, SAT-2 and GalNAcT-1 mRNA in colon cancer by real-time PCR. Molecular and cellular biochemistry 4 17119850
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