Affinage

SLC23A2

Solute carrier family 23 member 2 · UniProt Q9UGH3

Length
650 aa
Mass
70.3 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC23A2 (SVCT2) is a plasma-membrane sodium-dependent ascorbate cotransporter that mediates the concentrative, secondary-active uptake of vitamin C into metabolically active cells, with a Km of ~69 µM and a 2:1 Na⁺:ascorbate stoichiometry (PMID:10471399). It serves as the principal or sole active ascorbate transporter in diverse cell types including astrocytes (PMID:11036152), chondrocytes—which concentrate ascorbate ~960-fold (PMID:15921655)—Schwann cells (PMID:19672970), bone marrow stromal cells (PMID:23089627), and neurons (PMID:19054284), and concentrates ascorbate in specialized brain cells such as apically polarized hypothalamic tanycytes (PMID:15625716) and radial glia (PMID:38180226). In polarized epithelia SVCT2 is sorted to the basolateral membrane through a hierarchically dominant N-terminal basolateral targeting sequence, with a C-terminal element required for plasma-membrane incorporation (PMID:15993839, PMID:19216494). Surface levels are dynamically tuned by ascorbate itself through a fast endocytic-recycling route and a slower ER/Golgi secretory route (PMID:29545069). Genetic loss of SVCT2 in mice depletes ascorbate in fetal cortex, placenta, and lung and is essential for life, impairing adrenal catecholamine synthesis via ascorbate-dependent dopamine β-hydroxylase and producing cortical hemorrhage and oxidative damage (PMID:12897061, PMID:20541602). SVCT2 supports tissue-building programs including osteogenic differentiation of stromal cells (PMID:23089627), neuronal branching and synaptic protein expression (PMID:26646539, PMID:34573045), and neural progenitor migration via CDC42/F-actin (PMID:31607868). Its transcription is governed by an exon 1b promoter driven by YY1 cooperating with Sp factors (PMID:21335086) and a cell-specific exon 1a promoter controlled by NF-Y/USF complexes silenced by CpG methylation at the USF site (PMID:21770893), with repression by p53/HDAC3 (PMID:33580460) and redox-driven induction through NF-κB, AP-1, and PKCβ/MEK-ERK signaling (PMID:17643393, PMID:19232538). Protein stability is set by an ERα–XIAP axis in which XIAP-mediated ubiquitination targets SVCT2 for degradation unless antagonized by ERα binding (PMID:40731045). Beyond ascorbate, SVCT2 also transports urate in a manner competitively inhibited by ascorbate (PMID:37390985).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing that hSVCT2 is itself a sodium-coupled ascorbate transporter defined the molecular identity and energetic basis of cellular vitamin C uptake.

    Evidence Functional expression of hSVCT2 cDNA in mammalian cells with radiolabeled ascorbate uptake and Na⁺ activation kinetics

    PMID:10471399

    Open questions at the time
    • No structural model of the transporter
    • Substrate translocation mechanism not resolved at atomic level
  2. 2000 Medium

    Mapping SVCT2 expression in brain and demonstrating it sets steady-state intracellular ascorbate clarified which CNS cells depend on this transporter under baseline conditions.

    Evidence Northern blot, in situ hybridization, and functional uptake/mathematical modeling in neurons and cultured astrocytes

    PMID:10841345 PMID:11036152

    Open questions at the time
    • In vivo astrocytic expression initially appeared culture-artifactual
    • Did not address injury-induced expression
  3. 2003 High

    Genetic knockout established that SVCT2 is physiologically essential, particularly for ascorbate-dependent adrenal catecholamine synthesis, moving it from a transporter to a required component of endocrine and developmental physiology.

    Evidence SVCT2 null mouse with HPLC catecholamine measurement, chromaffin cell ultrastructure, and tissue ascorbate quantification; MCAO ischemia ISH

    PMID:12887688 PMID:12897061

    Open questions at the time
    • Mechanism linking ascorbate to dopamine β-hydroxylase activity inferred rather than directly assayed
    • Injury-induced astrocytic upregulation mechanism unresolved
  4. 2005 High

    Identification of the N-terminal basolateral targeting sequence answered how SVCT2 achieves polarized localization distinct from SVCT1.

    Evidence EGFP-tagged constructs with domain swaps and mutagenesis in MDCK/Caco-2 cells plus Transwell transport assays; tanycyte ISH/immunoEM/uptake

    PMID:15625716 PMID:15993839 PMID:19216494

    Open questions at the time
    • Trafficking adaptors recognizing the BTS not identified
    • Apical localization in tanycytes/radial glia uses a different determinant not defined
  5. 2009 High

    Dissecting the dual exon 1a/1b promoters and the PKCβ→MEK/ERK induction cascade established how SVCT2 expression is cell-type-specifically and inducibly controlled.

    Evidence Promoter deletion/reporter assays, EMSA supershifts, bisulfite methylation/demethylation, and isoform-selective inhibitor studies in THP-1 and multiple cell lines

    PMID:19232538 PMID:21335086 PMID:21770893

    Open questions at the time
    • Relative usage of the two promoters across tissues not quantified
    • Upstream signals selecting promoter usage incompletely mapped
  6. 2010 High

    Loss-of-function in primary cells and feedback by intracellular ascorbate showed SVCT2 is the dominant active uptake route and is homeostatically autoregulated.

    Evidence siRNA/shRNA knockdown and phloretin inhibition in Schwann cells and BMSCs; ascorbate-synthesis-deficient SMP30/GNL KO hepatocytes; KO mouse oxidative-stress biomarkers

    PMID:19672970 PMID:20122894 PMID:20541602

    Open questions at the time
    • Molecular sensor coupling intracellular ascorbate to expression not identified
    • Tissue-specific feedback thresholds undefined
  7. 2012 Medium

    Linking SVCT2 to osteogenic differentiation and redox-modulated expression connected the transporter to stem cell fate decisions.

    Evidence Lentiviral shRNA knockdown with osteogenic differentiation assays, kinetic transport characterization, and redox treatments in BMSCs; SVCT2-Tg gain-of-function mice

    PMID:22558179 PMID:22763122 PMID:23089627

    Open questions at the time
    • Direct ascorbate-dependent enzymatic step driving osteogenesis not pinpointed
    • Cardiomyocyte data lack genetic confirmation
  8. 2014 Medium

    Discovery of a dominant-negative short isoform and gain-of-function neuronal effects revealed post-translational and morphogenic layers of SVCT2 regulation.

    Evidence FRET interaction of SVCT2sh with SVCT2wt plus uptake assays; lentiviral SVCT2-EYFP overexpression with MAP2/filopodia imaging and ERK phosphorylation in N2a cells

    PMID:24947427 PMID:26646539

    Open questions at the time
    • Physiological abundance and regulation of the short isoform unknown
    • Whether ERK activation is direct or downstream of ascorbate cofactor functions unresolved
  9. 2015 Medium

    Identification of miRNA repression (miR-141/miR-200a, later miR-125a-5p) added post-transcriptional control to SVCT2 regulation in differentiation and injury.

    Evidence 3'-UTR luciferase reporters, miRNA mimics/inhibitors, and functional differentiation/uptake readouts in BMSCs and cortical neurons

    PMID:25617715 PMID:27085842

    Open questions at the time
    • In vivo contribution of these miRNAs to SVCT2 levels not established
    • Combinatorial miRNA regulation not modeled
  10. 2018 High

    Resolving two distinct ascorbate-driven trafficking routes explained how surface SVCT2 abundance is dynamically tuned by substrate availability.

    Evidence RUSH synchronized ER-to-PM trafficking, dominant-negative dynamin II/AP180/Rab11, brefeldin A/tunicamycin, and surface biotinylation/uptake assays

    PMID:29545069

    Open questions at the time
    • Signal transducing extracellular ascorbate to trafficking machinery not identified
    • Cell-type generality of dual routes untested
  11. 2021 Medium

    Demonstration of p53/HDAC3 repression, ER localization, and vitamin C recycling-dependent neuronal effects integrated SVCT2 into epigenetic, organellar, and intercellular metabolic control.

    Evidence ChIP for p53/HDAC3 and histone acetylation with promoter mutagenesis; SVCT2 colocalization with ER markers; SVCT2 genetic models with GLUT1 inhibition in glia

    PMID:33580460 PMID:34573045

    Open questions at the time
    • Functional role of ER-localized SVCT2 not defined
    • Direct downstream ascorbate-dependent enzymes in branching not pinpointed
  12. 2021 Low

    Proposal of SVCT2 as a receptor-like transporter activating JAK2/STAT2 introduced a putative signaling function beyond transport.

    Evidence Co-immunoprecipitation of SVCT2–JAK2 and phosphorylation assays with mutant constructs

    PMID:33484802

    Open questions at the time
    • Single Co-IP/phosphorylation study not independently replicated
    • Whether signaling is separable from transport activity unestablished
    • Physiological relevance in vivo untested
  13. 2023 Medium

    Identification of urate as a second SVCT2 substrate competitively inhibited by ascorbate broadened the transporter's physiological substrate scope.

    Evidence SVCT2-expressing mammalian cell urate uptake assays with ascorbate inhibition kinetics, confirmed in mouse Svct2

    PMID:37390985

    Open questions at the time
    • In vivo contribution to urate handling not established
    • Stoichiometry and physiological flux of urate transport unquantified
  14. 2023 Medium

    Defining NF-κB-dependent bidirectional regulation of SVCT2 in melanoma and lens epithelium tied transporter levels to oxidative-stress outcomes including ferroptosis and apoptosis.

    Evidence Blue-light and UVB models with NF-κB/ROS inhibitors, siRNA knockdown, and ascorbate uptake/ferroptosis-apoptosis markers

    PMID:37246402 PMID:37276798

    Open questions at the time
    • Context determining whether NF-κB induces vs represses SVCT2 unresolved
    • Direct NF-κB binding to SVCT2 promoter not demonstrated in these studies
  15. 2025 Medium

    Discovery of the ERα–XIAP axis controlling SVCT2 protein stability and microglial gain-of-function neuroprotection extended SVCT2 regulation to ubiquitin-mediated turnover and disease-modifying roles.

    Evidence Co-IP, XIAP/ERα siRNA, ubiquitination and proteasome-rescue assays; microglial-targeted SVCT2 overexpression in 5xFAD mice with plaque/synaptic/behavioral readouts

    PMID:40731045 PMID:40907096

    Open questions at the time
    • XIAP ubiquitination sites on SVCT2 not mapped
    • Mechanism by which microglial SVCT2 reprograms phenotype incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The transporter responsible for basolateral ascorbate efflux and the structural basis of SVCT2 substrate selection between ascorbate and urate remain unidentified.
  • SLC23A2 does not mediate ascorbate efflux and the efflux carrier is unknown [#23]
  • No atomic structure to explain dual ascorbate/urate transport
  • Signaling vs transport functions not mechanistically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0140104 molecular carrier activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 2 GO:0005768 endosome 1
Pathway
R-HSA-382551 Transport of small molecules 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ESR1JAK2SLC23A2XIAP

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human SVCT2 (hSVCT2) encodes a 650 amino acid, ~70 kDa protein that mediates sodium-dependent, saturable transport of ascorbic acid with a Km of 69 µM and a Na⁺:ascorbate stoichiometry of 2:1, establishing it as a secondary active transporter. Functional expression of hSVCT2 cDNA in mammalian cells; radiolabeled ascorbate uptake assays; Na⁺ activation kinetics Biochemical and biophysical research communications High 10471399
2005 In polarized epithelial cells (Caco-2 and MDCK), SVCT2-EGFP localizes predominantly to the basolateral membrane, whereas SVCT1 localizes apically; basolateral SVCT2 function was confirmed by ascorbate uptake assays with basolateral membrane exposure. An N-terminal basolateral targeting sequence (BTS) conserved among mammalian SVCT2 forms is responsible for this sorting. EGFP-tagged SVCT constructs expressed in MDCK and Caco-2 cells; confocal microscopy; Transwell ascorbate transport assays; domain-swap and point-mutation analysis Biochemical and biophysical research communications / Biochemistry High 15993839 19216494
2000 SVCT2 is expressed in cultured astrocytes (Northern blot) but in situ hybridization detects SVCT2 mRNA only in neurons and not in normal astrocytes in vivo, indicating that astrocyte SVCT2 expression is an artifact of culture conditions and that in the intact brain SVCT2 is neuron-specific. Northern blot analysis of cultured astrocytes; in situ hybridization on brain sections; quinolinic acid neurotoxin challenge model Neuroreport Medium 10841345
2000 SVCT2-mediated Na⁺-ascorbate cotransport across the plasma membrane is the primary determinant of steady-state intracellular ascorbic acid concentration in primary astrocyte cultures; transport activity and intracellular ascorbate are modulated by cAMP, hyposmotic swelling, and extracellular Na⁺ and K⁺ levels. SVCT2 expression detected by Northern blot in rat brain and cultured astrocytes; mathematical modeling validated against experimental ascorbate uptake measurements under varying ionic and osmotic conditions Brain research Medium 11036152
2001 SVCT2 (but not SVCT1) mediates Na⁺-dependent, saturable ascorbic acid uptake in human lens epithelial cells (HLE-B3); SVCT2 gene expression is upregulated by oxidant stress (tert-butylhydroperoxide), and uptake is partially modulated by cAMP, cytochalasin B, and phorbol ester signaling. RT-PCR for SVCT isoform identification; radiolabeled (¹⁴C) ascorbate uptake assays; inhibitor studies; gene expression analysis Experimental eye research Medium 11446766
2003 SVCT2 null mice show severely reduced ascorbic acid in fetal cortex, placenta, and lung (but not liver, the site of synthesis); adrenal medullary catecholamine synthesis is impaired—norepinephrine decreased 50%, epinephrine 81%—with depletion of chromaffin cell secretory vesicles and increased apoptosis, establishing SVCT2 as essential for ascorbate-dependent dopamine β-hydroxylase activity in the adrenal medulla. SVCT2 knockout mouse model; HPLC catecholamine measurements; electron microscopy of chromaffin cells; plasma corticosterone assay FASEB journal High 12897061
2003 Focal cerebral ischemia (middle cerebral artery occlusion) upregulates SVCT2 mRNA in both neurons and astrocytes in the peri-infarct zone, providing in situ evidence for SVCT2 expression in reactive astrocytes—the first demonstration of astrocytic SVCT2 in situ. In situ hybridization on rat brain sections 2 h and 22 h after MCAO Journal of neurochemistry Medium 12887688
2005 SVCT2 is highly expressed in the apical membranes of hypothalamic tanycytes (specialized ependymal/glial cells) and mediates high-affinity ascorbic acid uptake in these cells, providing the mechanism by which ascorbate is concentrated in the hypothalamic region. In situ hybridization; ultrastructural immunocytochemistry; primary tanycyte cultures with functional ascorbate uptake assays Glia High 15625716
2005 SVCT2 is the sole active transporter for ascorbic acid in primary human chondrocytes; siRNA knockdown of SVCT2 abolishes the active (Na⁺-dependent, saturable, concentrative) component of ascorbate transport, and these cells can concentrate ascorbate ~960-fold over extracellular levels. Radiolabeled ascorbate uptake assays; RT-PCR isoform identification; siRNA knockdown of SVCT2 Biochimica et biophysica acta High 15921655
2006 SVCT2 expression in anucleated human platelets is regulated at the translational level; platelets compensate for fluctuations in ascorbate levels by modulating SVCT2 protein expression post-transcriptionally, and SVCT2 upregulation occurs during platelet activation accompanied by vitamin C depletion. Western blot and functional ascorbate uptake in isolated anucleated platelets; platelet activation assays Free radical biology & medicine Medium 17291984
2007 SVCT2 transcription in C2C12 myotubes is redox-regulated: H₂O₂ upregulates SVCT2 gene expression and lipoate (antioxidant) downregulates it, with the effect mediated through AP-1 and NF-κB signaling pathways. SVCT2 mRNA quantification in C2C12 myotubes treated with H₂O₂ or lipoate; pharmacological inhibition of AP-1/NF-κB Biochemical and biophysical research communications Medium 17643393
2008 SVCT2 is expressed and functional in rat brainstem cells, cortical neurons, cerebellar neurons, and neuroblastoma cells; the transporter displays two kinetically distinct affinity components for ascorbate, and flavonoids (notably quercetin) dose-dependently inhibit SVCT2-mediated ascorbate transport. RT-PCR; immunohistochemistry/ISH in fetal and adult rat brain; radiolabeled ascorbate uptake kinetics; dose-response inhibition with flavonoids Journal of neurochemistry Medium 19054284
2009 PMA-induced monocyte-to-macrophage differentiation markedly increases SVCT2 mRNA, protein, and transport function through a pathway requiring sustained activation of PKCβI/II → MEK/ERK (MAP kinase), with additional contributions from NADPH oxidase, NF-κB, and both known SVCT2 promoters. THP-1 monocyte differentiation model; SVCT2 mRNA/protein quantification; pharmacological inhibition of PKC isoforms (isoform-selective inhibitors), MEK/ERK, NF-κB, NADPH oxidase; promoter reporter assays Free radical biology & medicine High 19232538
2009 SVCT2 in epithelial cells contains a hierarchically dominant N-terminal basolateral targeting sequence (BTS) and a C-terminal sequence required for plasma membrane incorporation and retention; deletion of the BTS redirects SVCT2 to the apical membrane, and C-terminal deletion results in intracellular accumulation regardless of the BTS. Domain-swap, deletion, insertion, and point-mutation of EGFP-tagged SVCT1/SVCT2 constructs stably expressed in MDCK cells; confocal microscopy; Transwell ascorbate transport assays Biochemistry High 19216494
2010 SVCT2 null mice exhibit reduced vitamin C levels in fetal placenta and cortex (but not liver), elevated oxidative stress markers (malondialdehyde, isoketals, F₂-isoprostanes, F₄-neuroprostanes), cortical and brainstem hemorrhage, increased apoptosis, and basement membrane disruption, establishing that SVCT2 is critical for maintaining fetal vitamin C levels and survival. SVCT2 knockout mouse model; HPLC ascorbate measurements; lipid peroxidation biomarkers; immunohistochemistry for apoptosis and basement membrane proteins Free radical biology & medicine High 20541602
2010 SVCT2 is the primary mediator of ascorbic acid uptake into Schwann cells; siRNA-mediated knockdown and phloretin inhibition significantly reduce ¹⁴C-ascorbate uptake, and SVCT2 is localized to uncompacted myelin compartments of Schwann cells, with transport activity dependent on extracellular Na⁺, Mg²⁺, and Ca²⁺. Immunohistochemistry, immunoblotting, RT-PCR in peripheral nerve and Schwann cell cultures; ¹⁴C-ascorbate uptake assays; siRNA knockdown; phloretin inhibition; ex vivo uptake in sciatic nerve Glia High 19672970
2010 Ascorbic acid depletion in SMP30/GNL knockout mouse hepatocytes enhances SVCT2 (and SVCT1) mRNA expression and increases ascorbate uptake, demonstrating that intracellular ascorbic acid negatively regulates SVCT2 expression in the liver. SMP30/GNL KO mouse model (ascorbate synthesis-deficient); SVCT mRNA quantification in tissues; primary hepatocyte culture ascorbate uptake assays Archives of biochemistry and biophysics Medium 20122894
2011 The SVCT2 exon 1b promoter (CpG-rich, ubiquitously expressed) is regulated by a functional initiator that binds YY1, which cooperates with upstream Sp1/Sp3 elements; YY1/Sp1 and YY1/Sp3 complexes synergistically activate the exon 1b promoter, and EGR-1, EGR-2, WT1, and MAZ differentially regulate activity through overlapping GC-box elements. Promoter deletion constructs; EMSA with YY1/Sp antibody supershifts; co-transfection reporter assays in multiple cell lines Free radical biology & medicine Medium 21335086
2011 Cell-specific transcription from the CpG-poor SVCT2 exon 1a promoter is controlled by cooperative binding of NF-Y and USF to Y-box and E-box elements; CpG methylation at the upstream USF-binding site impairs both USF binding and NF-Y/USF complex formation, silencing exon 1a transcription in a cell-type-specific manner. Promoter deletion/mutation constructs; EMSA with antibody supershifts; bisulfite methylation analysis; decitabine demethylation experiments; co-transfection reporter assays The Biochemical journal High 21770893
2012 SVCT2 is expressed in bone marrow stromal cells (BMSCs) as the sole ascorbate transporter; SVCT2 expression is upregulated during osteogenic differentiation (maximal at earliest phase), and lentiviral shRNA knockdown of SVCT2 inhibits osteogenesis; redox status positively (oxidant Sin-1) or negatively (ascorbic acid) modulates SVCT2 expression in BMSCs. RT-PCR; ¹⁴C-ascorbate uptake assays (Na⁺-dependent, saturable); lentiviral shRNA KD of SVCT2; osteogenic differentiation assays; redox treatments Stem cell research High 23089627
2012 Doxorubicin reduces SVCT2 expression and localization at the sarcolemma of cardiomyocytes; vitamin C supplementation blunts this reduction, suggesting that SVCT2 downregulation contributes to doxorubicin-induced cardiotoxicity by impairing ascorbate uptake. Isolated rat cardiomyocytes; Western blot and immunofluorescence localization of SVCT2; oxidative stress and apoptosis markers American journal of physiology. Cell physiology Medium 22763122
2012 SVCT2 transgenic mice (global SVCT2 overexpression) show increased SVCT2 mRNA and correspondingly increased ascorbic acid levels in all organs except liver; this elevated ascorbate protects against paraquat-induced oxidative stress in lung (reduced F₂-isoprostanes). SVCT2 transgenic mouse model; qRT-PCR; HPLC ascorbate measurements; F₂-isoprostane oxidative stress markers; paraquat oxidative challenge PloS one Medium 22558179
2013 SVCT2 knockdown in BMSCs decreases cell attachment, spreading, trans-well migration, and wound healing; supplementation with vitamin C rescues these defects in wild-type but not SVCT2-knockdown cells; SVCT2 KD and oxidative stress alter cytoskeletal (F-actin) dynamics and activate p38 MAPK phosphorylation, which is inhibited by vitamin C. Lentiviral shRNA SVCT2 knockdown in BMSCs; cell adhesion, trans-well migration, and scratch wound assays; F-actin staining; p38 MAPK phosphorylation Western blot Stem cell research Medium 24365600
2013 SLC23A2/SVCT2 does not mediate ascorbic acid efflux (release) in renal proximal tubular epithelial cells; SLC23A2 is not expressed in the human proximal tubule, and a Xenopus oocyte dual-transporter system confirmed that SLC23A1 also does not mediate basolateral ascorbate release, indicating the efflux mechanism remains unidentified. Xenopus laevis oocyte expression system (dual-transporter assay); mammalian cell overexpression; human tissue gene expression analysis Physiological reports Medium 24400138
2014 SVCT2 overexpression in N2a neuroblastoma cells induces increased MAP2+ neurites and filopodia formation; SVCT2 overexpression combined with ascorbate treatment promotes ERK1/2 phosphorylation, linking SVCT2-mediated ascorbate uptake to ERK signaling during neuronal branching. Lentiviral SVCT2-EYFP overexpression in N2a cells; immunofluorescence for MAP2 and filopodia; Western blot for ERK1/2 phosphorylation Molecular neurobiology Medium 26646539
2014 A short isoform of SVCT2 (SVCT2sh) interacts physically with full-length SVCT2 (SVCT2wt), as shown by FRET, and co-expression of SVCT2sh inhibits ascorbate uptake by SVCT2wt in N2a cells, indicating that the short isoform acts as a dominant-negative regulator of transporter function. FRET analysis of co-expressed SVCT2wt and SVCT2sh in N2a cells; ¹⁴C-ascorbate uptake assays Journal of neurochemistry Medium 24947427
2015 miR-141 and miR-200a directly repress SVCT2 expression by targeting the 3'-UTR of SVCT2 mRNA in BMSCs, reducing osteogenic differentiation; miRNA inhibitors restore SVCT2 expression and osteogenic gene expression. 3'-UTR luciferase reporter assays; miRNA mimic and inhibitor transfections; SVCT2 protein quantification; osteogenic differentiation assays in mouse BMSCs Molecular and cellular endocrinology Medium 25617715
2016 SVCT2 upregulation in response to ethanol-induced neuronal injury is mediated by activation of JNK and p38 MAPKs and the NF-κB pathway; miR-125a-5p negatively regulates SVCT2 protein expression and is downregulated during binge drinking, and miR-125a-5p overexpression reduces SVCT2 levels and intracellular ascorbate, increasing neuronal vulnerability. Rat binge-drinking model; primary cortical neurons with SVCT2 siRNA; SVCT2 mRNA/protein quantification; MAPK and NF-κB phosphorylation Western blots; miR-125a-5p overexpression Free radical biology & medicine Medium 27085842
2018 Ascorbic acid increases SVCT2 levels at the plasma membrane via two distinct mechanisms: (1) an 'acute' response (~5–10 min) dependent on endocytic recycling (blocked by dominant-negative dynamin II, AP180, and Rab11); and (2) a 'post-acute' response (~30–60 min) dependent on SVCT2 trafficking from early secretory compartments (ER/Golgi), blocked by tunicamycin and brefeldin A and accelerated by the RUSH secretory system. RUSH system for synchronized ER-to-PM cargo trafficking; dominant-negative dynamin II, AP180, and Rab11 constructs; tunicamycin/brefeldin A treatment; surface biotinylation and ascorbate uptake assays Free radical biology & medicine High 29545069
2019 SVCT2 promotes migration of neural stem/progenitor cells (NSPCs) from the subventricular zone toward ischemic lesions by upregulating CDC42, which promotes F-actin assembly; SVCT2 overexpression or ascorbate treatment increases NSPC migration in vivo and in vitro under oxygen-glucose deprivation. SVCT2 overexpression vectors in vivo and in vitro; OGD cell model; immunostaining for CDC42 and F-actin; NSPC migration counting in vivo Frontiers in cellular neuroscience Medium 31607868
2021 SVCT2 is localized primarily in the cell membrane and endoplasmic reticulum (but not mitochondria) of cortical neurons; lentiviral SVCT2 overexpression increases neuronal branching and synaptic protein expression in primary cortical neurons, and this effect depends on vitamin C recycling between neurons and astrocytes (DHA produced by neurons is reduced back to ascorbate by glial GLUT1, and GLUT1 inhibition in glia abolishes branching both in vitro and in the cortex in situ). SVCT2 lentiviral overexpression; immunofluorescence colocalization with ER/mitochondrial markers; SVCT2+/- and SVCT2-Tg primary cultures; WZB117 GLUT1 inhibitor in vitro and in vivo; cortical neuron branching and synaptic protein quantification Antioxidants (Basel, Switzerland) Medium 34573045
2021 p53 directly represses SVCT2 transcription by binding proximal (~-185 to -171 bp) and distal (~-1800 to -1787 bp) p53-responsive elements in the SVCT2 promoter; chromatin immunoprecipitation shows p53 recruits corepressor HDAC3, leading to deacetylation of histone Ac-H4 at the proximal promoter and transcriptional silencing. ChIP assays for p53 and HDAC3 binding and histone acetylation; promoter reporter deletion/mutation assays; p53 overexpression/knockdown Molecular biology reports Medium 33580460
2021 SVCT2 functions as a receptor-like transporter: upon ascorbate binding and transport, SVCT2 induces JAK2 phosphorylation; activated JAK2 then phosphorylates the SVCT2 C-terminus, recruiting and activating STAT2; JAK2 activation further promotes ascorbate functions via phosphorylation of PDK1, TET3, and histone H3 Tyr41. Co-immunoprecipitation of SVCT2–JAK2 interaction; phosphorylation assays; SVCT2 mutant constructs; JAK2 and STAT2 activation readouts International journal of biological macromolecules Low 33484802
2022 SVCT2-mediated ascorbate uptake in the medial prefrontal cortex supports DNA hydroxymethylation reprogramming via TET dioxygenases; chronic stress reduces SVCT2 expression and ascorbate in the mPFC, causing depressive-like behaviors through reduced TET-dependent demethylation, particularly at the S100A4 gene promoter, which in turn impairs ErbB4–BDNF signaling. Chronic stress mouse model; SVCT2 expression quantification; ascorbate HPLC; transcriptome and methylome sequencing; TET inhibition; ErbB4/BDNF pathway analysis Redox biology Medium 36436457
2023 SVCT2 is a novel sodium-dependent urate transporter in addition to its ascorbate transport function; cell-based assays in SVCT2-expressing mammalian cells demonstrated urate uptake, and ascorbate inhibits SVCT2-mediated urate transport with an IC₅₀ of ~36.59 µM, suggesting competitive transport at physiological ascorbate concentrations. SVCT2-expressing mammalian cell-based urate uptake assay; inhibition studies with ascorbate; confirmation in mouse Svct2 The Journal of biological chemistry Medium 37390985
2023 Blue light irradiation specifically upregulates SVCT2 expression in melanoma cells via the NF-κB signaling pathway both in vitro and in vivo, increasing intracellular vitamin C and, together with Fe²⁺ generated by blue light, triggers ferroptosis. Blue light treatment of melanoma cells in vitro and mouse melanoma model in vivo; SVCT2 protein quantification; NF-κB inhibitor studies; ROS/ferroptosis markers Biomaterials Medium 37276798
2023 UVB-induced ROS in human lens epithelial cells activates NF-κB signaling, which downregulates SVCT2 expression; reduced SVCT2 decreases ascorbate uptake, further increasing ROS and apoptosis; NF-κB or ROS inhibition restores SVCT2 and reduces apoptosis, defining an NF-κB/SVCT2/ascorbate regulatory axis. UVB treatment of HLECs; SVCT2 siRNA knockdown; NF-κB inhibitor (PDTC) and ROS inhibitor (NAC); ¹⁴C-ascorbate uptake assays; ROS, apoptosis, and Bcl-2/Bax quantification Cell cycle (Georgetown, Tex.) Medium 37246402
2024 In late radial glia (lRG) cells in early postnatal cortex, SVCT2 is apically polarized; decreased SVCT2 (SVCT2+/- transgenic) accelerates lRG differentiation into astrocytes, whereas elevated SVCT2 expression (SVCT2-Tg) or ascorbate treatment maintains lRG in an undifferentiated state; in vivo SVCT2 overexpression in lRG generates migratory neuronal-marker-positive cells. The GSK3-β/AKT/mTORC2/PDK1 pathway is active in brains with high SVCT2/ascorbate levels. SVCT2+/- and SVCT2-Tg primary cultures and in vivo cortex; adenovirus-eGFP lineage tracing; immunofluorescence; GSK3-β/AKT/mTORC2 Western blots Glia Medium 38180226
2025 Estrogen receptor α (ERα) directly interacts with SVCT2 protein and stabilizes it; ERα knockdown reduces SVCT2 protein levels and ascorbate uptake. In ERα-deficient conditions, the E3 ubiquitin ligase XIAP ubiquitinates SVCT2 and targets it for proteasomal degradation; XIAP silencing rescues SVCT2 stability, defining an ERα–XIAP–SVCT2 regulatory axis. Co-immunoprecipitation of ERα–SVCT2; ERα and XIAP siRNA knockdown; proteasome inhibitor rescue; ¹⁴C-ascorbate uptake assays; ubiquitination assays Scientific reports Medium 40731045
2025 SVCT2 overexpression in microglia before disease onset in 5xFAD Alzheimer's mice triggers redox reprogramming, generates a hybrid neuroprotective microglial phenotype co-expressing homeostatic and disease-associated markers, reduces amyloid plaque burden, and prevents synaptic/memory deficits; post-disease SVCT2 overexpression rescues synaptic plasticity and memory via changes in microglial secretory pathways, despite no effect on existing amyloid burden. Microglial-targeted SVCT2 overexpression in 5xFAD mice; primary microglial cultures from SVCT2-het and Tg mice; amyloid plaque quantification; synaptic and memory behavioral assays; microglial morphology and mRNA profiling Redox biology Medium 40907096

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free radical biology & medicine 457 19162177
2007 SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino acids 284 17541511
1999 Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function. Biochemical and biophysical research communications 139 10471399
2018 Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2. NPJ precision oncology 108 29872720
2005 Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells. Glia 90 15625716
2005 Polarized localization of vitamin C transporters, SVCT1 and SVCT2, in epithelial cells. Biochemical and biophysical research communications 84 15993839
2010 Low vitamin C and increased oxidative stress and cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2. Free radical biology & medicine 77 20541602
2014 Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts. Journal of stem cell research & therapy 73 25110615
2012 Ascorbic acid enhances the expression of type 1 and type 4 collagen and SVCT2 in cultured human skin fibroblasts. Biochemical and biophysical research communications 69 23228664
2006 Translational control of the ascorbic acid transporter SVCT2 in human platelets. Free radical biology & medicine 69 17291984
2012 SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment. Oncogene 68 22665050
2003 Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 63 12897061
2003 Effect of middle cerebral artery occlusion on mRNA expression for the sodium-coupled vitamin C transporter SVCT2 in rat brain. Journal of neurochemistry 58 12887688
2005 Genetic variation in the sodium-dependent vitamin C transporters, SLC23A1, and SLC23A2 and risk for preterm delivery. American journal of epidemiology 57 16357110
2001 Vitamin C transport in human lens epithelial cells: evidence for the presence of SVCT2. Experimental eye research 53 11446766
2008 The Na+-dependent L-ascorbic acid transporter SVCT2 expressed in brainstem cells, neurons, and neuroblastoma cells is inhibited by flavonoids. Journal of neurochemistry 51 19054284
2018 Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression. Scientific reports 50 30054560
2010 Ascorbic acid depletion enhances expression of the sodium-dependent vitamin C transporters, SVCT1 and SVCT2, and uptake of ascorbic acid in livers of SMP30/GNL knockout mice. Archives of biochemistry and biophysics 50 20122894
2004 Comparison of the genomic structure and variation in the two human sodium-dependent vitamin C transporters, SLC23A1 and SLC23A2. Human genetics 48 15316768
2007 Redox regulation of vitamin C transporter SVCT2 in C2C12 myotubes. Biochemical and biophysical research communications 47 17643393
2011 Differential regulation of the ascorbic acid transporter SVCT2 during development and in response to ascorbic acid depletion. Biochemical and biophysical research communications 46 22001929
2009 Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer. Carcinogenesis 46 19346260
2011 Association between a SLC23A2 gene variation, plasma vitamin C levels, and risk of glaucoma in a Mediterranean population. Molecular vision 45 22171153
2009 Macrophage differentiation increases expression of the ascorbate transporter (SVCT2). Free radical biology & medicine 44 19232538
2014 Orally administrated ascorbic acid suppresses neuronal damage and modifies expression of SVCT2 and GLUT1 in the brain of diabetic rats with cerebral ischemia-reperfusion. Nutrients 42 24739976
2010 Sodium-dependent vitamin C transporter 2 (SVCT2) is necessary for the uptake of L-ascorbic acid into Schwann cells. Glia 41 19672970
2013 Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort. Genes & nutrition 40 23737080
2000 The vitamin C transporter SVCT2 is expressed by astrocytes in culture but not in situ. Neuroreport 40 10841345
2000 Sodium-ascorbate cotransport controls intracellular ascorbate concentration in primary astrocyte cultures expressing the SVCT2 transporter. Brain research 39 11036152
2012 Sodium-dependent vitamin C transporter SVCT2: expression and function in bone marrow stromal cells and in osteogenesis. Stem cell research 36 23089627
2017 SVCT-2 determines the sensitivity to ascorbate-induced cell death in cholangiocarcinoma cell lines and patient derived xenografts. Cancer letters 34 28385602
2016 SVCT2, a potential therapeutic target, protects against oxidative stress during ethanol-induced neurotoxicity via JNK/p38 MAPKs, NF-κB and miRNA125a-5p. Free radical biology & medicine 34 27085842
2015 MicroRNAs-141 and 200a regulate the SVCT2 transporter in bone marrow stromal cells. Molecular and cellular endocrinology 34 25617715
2011 Sodium-dependent vitamin C transporter 2 (SVCT2) expression and activity in brain capillary endothelial cells after transient ischemia in mice. PloS one 29 21347255
2016 Vitamin C is taken up by human T cells via sodium-dependent vitamin C transporter 2 (SVCT2) and exerts inhibitory effects on the activation of these cells in vitro. Anatomy & cell biology 28 27382510
2013 SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche. Frontiers in cellular neuroscience 28 23964197
2009 Hierarchal contribution of N- and C-terminal sequences to the differential localization of homologous sodium-dependent vitamin C transporters, SVCT1 and SVCT2, in epithelial cells. Biochemistry 27 19216494
2019 SVCT2 Promotes Neural Stem/Progenitor Cells Migration Through Activating CDC42 After Ischemic Stroke. Frontiers in cellular neuroscience 26 31607868
2013 Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells. Stem cell research 25 24365600
2014 SVCT2 transporter expression is post-natally induced in cortical neurons and its function is regulated by its short isoform. Journal of neurochemistry 22 24947427
2012 Downregulation of vitamin C transporter SVCT-2 in doxorubicin-induced cardiomyocyte injury. American journal of physiology. Cell physiology 22 22763122
2005 Chondrocyte transport and concentration of ascorbic acid is mediated by SVCT2. Biochimica et biophysica acta 22 15921655
2021 SVCT2 Overexpression and Ascorbic Acid Uptake Increase Cortical Neuron Differentiation, Which Is Dependent on Vitamin C Recycling between Neurons and Astrocytes. Antioxidants (Basel, Switzerland) 21 34573045
2015 The crucial role of vitamin C and its transporter (SVCT2) in bone marrow stromal cell autophagy and apoptosis. Stem cell research 21 26210298
2019 Enhanced Anticancer Effect of Adding Magnesium to Vitamin C Therapy: Inhibition of Hormetic Response by SVCT-2 Activation. Translational oncology 19 31901552
2014 High-dose vitamin C supplementation increases skeletal muscle vitamin C concentration and SVCT2 transporter expression but does not alter redox status in healthy males. Free radical biology & medicine 19 25242204
2012 Increased expression of SVCT2 in a new mouse model raises ascorbic acid in tissues and protects against paraquat-induced oxidative damage in lung. PloS one 19 22558179
2023 Role of vitamin C and SVCT2 in neurogenesis. Frontiers in neuroscience 18 37424994
2013 Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy. Medical hypotheses 18 23916956
2013 The human sodium-dependent ascorbic acid transporters SLC23A1 and SLC23A2 do not mediate ascorbic acid release in the proximal renal epithelial cell. Physiological reports 18 24400138
2009 The ascorbic acid transporter SVCT2 is expressed in slow-twitch skeletal muscle fibres. Histochemistry and cell biology 18 19125272
2001 Characterization of the genomic structure of the human vitamin C transporter SVCT1 (SLC23A2). The Journal of nutrition 18 11584081
2023 Blue light promotes vitamin C-mediated ferroptosis of melanoma through specifically upregulating transporter SVCT2 and generating Fe2. Biomaterials 17 37276798
2017 SVCT2 Expression and Function in Reactive Astrocytes Is a Common Event in Different Brain Pathologies. Molecular neurobiology 17 28942474
2012 Dynamic expression of the sodium-vitamin C co-transporters, SVCT1 and SVCT2, during perinatal kidney development. Histochemistry and cell biology 17 22990596
2022 SVCT2-mediated ascorbic acid uptake buffers stress responses via DNA hydroxymethylation reprogramming of S100 calcium-binding protein A4 gene. Redox biology 16 36436457
2017 Ascorbic acid drives the differentiation of mesoderm-derived embryonic stem cells. Involvement of p38 MAPK/CREB and SVCT2 transporter. Molecular nutrition & food research 16 27957816
2017 SVCT2 Is Expressed by Cerebellar Precursor Cells, Which Differentiate into Neurons in Response to Ascorbic Acid. Molecular neurobiology 16 28097475
2015 SVCT2 Overexpression in Neuroblastoma Cells Induces Cellular Branching that is Associated with ERK Signaling. Molecular neurobiology 16 26646539
2013 Sodium-coupled vitamin C transporter (SVCT2): expression, function, and regulation in intervertebral disc cells. The spine journal : official journal of the North American Spine Society 15 23415019
2023 Ultraviolet B radiation induces oxidative stress and apoptosis in human lens epithelium cells by activating NF-κB signaling to down-regulate sodium vitamin C transporter 2 (SVCT2) expression. Cell cycle (Georgetown, Tex.) 14 37246402
2016 Apical Polarization of SVCT2 in Apical Radial Glial Cells and Progenitors During Brain Development. Molecular neurobiology 14 27596508
2005 Functional analysis of two regulatory regions of the human Na+ -dependent vitamin C transporter 2, SLC23A2, in human vascular smooth muscle cells. Biochimica et biophysica acta 14 16380174
2019 Data on SVCT2 transporter expression and localization in cancer cell lines and tissues. Data in brief 13 31249848
2014 Functional characterization and molecular identification of vitamin C transporter (SVCT2) in human corneal epithelial (HCEC) and retinal pigment epithelial (D407) cells. Current eye research 13 25014399
2014 Molecular expression and functional activity of vitamin C specific transport system (SVCT2) in human breast cancer cells. International journal of pharmaceutics 13 25102111
2011 Regulation of the human ascorbate transporter SVCT2 exon 1b gene by zinc-finger transcription factors. Free radical biology & medicine 13 21335086
2011 CpG methylation at the USF-binding site mediates cell-specific transcription of human ascorbate transporter SVCT2 exon 1a. The Biochemical journal 13 21770893
2009 Oxidized lipoprotein induces the macrophage ascorbate transporter (SVCT2): protection by intracellular ascorbate against oxidant stress and apoptosis. Archives of biochemistry and biophysics 13 19254685
2021 New insights into Vitamin C function: Vitamin C induces JAK2 activation through its receptor-like transporter SVCT2. International journal of biological macromolecules 12 33484802
2018 Ascorbic acid increases SVCT2 localization at the plasma membrane by accelerating its trafficking from early secretory compartments and through the endocytic-recycling pathway. Free radical biology & medicine 12 29545069
2013 Liver metabolic/oxidative stress induces hepatic and extrahepatic changes in the expression of the vitamin C transporters SVCT1 and SVCT2. European journal of nutrition 12 23708151
2016 Fruit and vegetable intake and vitamin C transporter gene (SLC23A2) polymorphisms in chronic lymphocytic leukaemia. European journal of nutrition 11 26838684
2012 Combined vitamin C and E deficiency induces motor defects in gulo(-/-)/SVCT2(+/-) mice. Nutritional neuroscience 11 23321552
2010 Oxidized LDL up-regulates the ascorbic acid transporter SVCT2 in endothelial cells. Molecular and cellular biochemistry 11 20549544
2010 Up-regulation of the vitamin C transporter SVCT2 upon differentiation and depolarization of myotubes. FEBS letters 11 21176777
2021 Ascorbic acid analogue 6-Deoxy-6-[18F] fluoro-L-ascorbic acid as a tracer for identifying human colorectal cancer with SVCT2 overexpression. Translational oncology 10 33677235
2023 SVCT2-GLUT1-mediated ascorbic acid transport pathway in rat dental pulp and its effects during wound healing. Scientific reports 9 36690706
2014 Genetic polymorphisms in SLC23A2 as predictive biomarkers of severe acute toxicities after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma. International journal of medical sciences 9 24578608
2012 Interaction of the transcription start site core region and transcription factor YY1 determine ascorbate transporter SVCT2 exon 1a promoter activity. PloS one 9 22532872
2023 Curcumin inhibits human cancer cell growth and migration through downregulation of SVCT2. Cell biochemistry and function 8 37322603
2014 SLC23A2-05 (rs4987219) and KRAS-LCS6 (rs61764370) polymorphisms in patients with squamous cell carcinoma of the head and neck. Oncology letters 8 24932237
2023 SVCT2/SLC23A2 is a sodium-dependent urate transporter: functional properties and practical application. The Journal of biological chemistry 7 37390985
2023 Construction of a Brain-specific SLC23A2 Gene Knockout Mice Model. Neuroscience 6 37330196
2020 SVCT2-Dependent plasma and mitochondrial membrane transport of ascorbic acid in differentiating myoblasts. Pharmacological research 6 32580031
2021 Role of p53 in transcriptional repression of SVCT2. Molecular biology reports 5 33580460
2019 Association of Leukemia Target Genes Tet2, Bcl2, and Slc23a2 in Vitamin C Pathways. Cancer genomics & proteomics 5 31467227
2024 Ascorbic acid and its transporter SVCT2, affect radial glia cells differentiation in postnatal stages. Glia 4 38180226
2013 The vitamin C transporter SVCT2 is down-regulated during postnatal development of slow skeletal muscles. Histochemistry and cell biology 4 23329419
2025 SVCT2-targeted PET imaging agent for the evaluation of LN metastasis of thyroid cancer. Bioorganic chemistry 3 39855109
2022 ATRX-dependent SVCT2 mediates macrophage infiltration in the glioblastoma xenograft model. Journal of neurophysiology 3 35417255
2021 Mutation SVCT2 promotes cell proliferation, invasion and migration in colorectal cancer. Journal of Cancer 3 34405001
2016 Temporo-spacial microanatomical distribution of the murine sodium-dependent ascorbic acid transporters Slc23a1 and Slc23a2 in the kidney throughout development. Biochemistry and cell biology = Biochimie et biologie cellulaire 3 28177761
2011 Molecular characterization and transcriptional regulation of the sodium-dependent vitamin C transporter genes (slc23a1 and slc23a2) in a teleost fish, the Senegalese sole (Solea senegalensis). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 3 22142801
2025 Oxidative stress-mediated apoptosis via the SLC23A2-ascorbic acid interaction contributes to cleft lip development. Frontiers in pediatrics 1 41113559
2024 Modulation of microglia activation by the ascorbic acid transporter SVCT2. Brain, behavior, and immunity 1 38972487
2025 Novel susceptibility gene SLC23A2 functions via PI3K-AKT-mTOR pathway in etiology of non-syndromic cleft palate. Journal of human genetics 0 40456835
2025 Estrogen receptor α regulates SVCT2 protein level in human breast cancer cells. Scientific reports 0 40731045
2025 Enhancing microglial antioxidant capacity via the ascorbate transporter SVCT2 delays onset and modifies disease progression in mouse models of Alzheimer's disease. Redox biology 0 40907096
2022 Impact of SLC23A1 and SLC23A2 Polymorphisms on the Risk for Preeclampsia in a Chinese Han Population. Journal of nutritional science and vitaminology 0 36310070

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